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1.
Int J Mol Sci ; 22(22)2021 Nov 12.
Artículo en Inglés | MEDLINE | ID: mdl-34830120

RESUMEN

Retinoic acid (RA), the principal active metabolite of vitamin A, is known to be involved in stress-related disorders. However, its mechanism of action in this regard remains unclear. This study reports that, in mice, endogenous cellular RA binding protein 1 (Crabp1) is highly expressed in the hypothalamus and pituitary glands. Crabp1 knockout (CKO) mice exhibit reduced anxiety-like behaviors accompanied by a lowered stress induced-corticosterone level. Furthermore, CRH/DEX tests show an increased sensitivity (hypersensitivity) of their feedback inhibition in the hypothalamic-pituitary-adrenal (HPA) axis. Gene expression studies show reduced FKBP5 expression in CKO mice; this would decrease the suppression of glucocorticoid receptor (GR) signaling thereby enhancing their feedback inhibition, consistent with their dampened corticosterone level and anxiety-like behaviors upon stress induction. In AtT20, a pituitary gland adenoma cell line elevating or reducing Crabp1 level correspondingly increases or decreases FKBP5 expression, and its endogenous Crabp1 level is elevated by GR agonist dexamethasone or RA treatment. This study shows, for the first time, that Crabp1 regulates feedback inhibition of the the HPA axis by modulating FKBP5 expression. Furthermore, RA and stress can increase Crabp1 level, which would up-regulate FKBP5 thereby de-sensitizing feedback inhibition of HPA axis (by decreasing GR signaling) and increasing the risk of stress-related disorders.


Asunto(s)
Ansiedad/fisiopatología , Homeostasis/fisiología , Sistema Hipotálamo-Hipofisario/metabolismo , Sistema Hipófiso-Suprarrenal/metabolismo , Receptores de Ácido Retinoico/metabolismo , Proteínas de Unión a Tacrolimus/metabolismo , Animales , Ansiedad/genética , Línea Celular Tumoral , Dexametasona/farmacología , Retroalimentación Fisiológica/efectos de los fármacos , Retroalimentación Fisiológica/fisiología , Regulación de la Expresión Génica/efectos de los fármacos , Homeostasis/genética , Hipotálamo/metabolismo , Masculino , Aprendizaje por Laberinto/fisiología , Ratones Endogámicos C57BL , Ratones Noqueados , Actividad Motora/genética , Actividad Motora/fisiología , Hipófisis/metabolismo , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismo , Receptores de Ácido Retinoico/genética , Proteínas de Unión a Tacrolimus/genética
2.
Elife ; 102021 09 14.
Artículo en Inglés | MEDLINE | ID: mdl-34517941

RESUMEN

Microsatellite expansions of CCTG repeats in the cellular nucleic acid-binding protein (CNBP) gene leads to accumulation of toxic RNA and have been associated with myotonic dystrophy type 2 (DM2). However, it is still unclear whether the dystrophic phenotype is also linked to CNBP decrease, a conserved CCHC-type zinc finger RNA-binding protein that regulates translation and is required for mammalian development. Here, we show that depletion of Drosophila CNBP in muscles causes ageing-dependent locomotor defects that are correlated with impaired polyamine metabolism. We demonstrate that the levels of ornithine decarboxylase (ODC) and polyamines are significantly reduced upon dCNBP depletion. Of note, we show a reduction of the CNBP-polyamine axis in muscles from DM2 patients. Mechanistically, we provide evidence that dCNBP controls polyamine metabolism through binding dOdc mRNA and regulating its translation. Remarkably, the locomotor defect of dCNBP-deficient flies is rescued by either polyamine supplementation or dOdc1 overexpression. We suggest that this dCNBP function is evolutionarily conserved in vertebrates with relevant implications for CNBP-related pathophysiological conditions.


Asunto(s)
Proteínas de Drosophila/metabolismo , Actividad Motora/genética , Actividad Motora/fisiología , Poliaminas/metabolismo , Proteínas de Unión al ARN/metabolismo , Animales , Animales Modificados Genéticamente , Línea Celular , Regulación hacia Abajo/fisiología , Proteínas de Drosophila/genética , Drosophila melanogaster , Regulación de la Expresión Génica/efectos de los fármacos , Células HEK293 , Humanos , Músculo Esquelético/metabolismo , Distrofia Miotónica/genética , Distrofia Miotónica/metabolismo , Biosíntesis de Proteínas , Putrescina/farmacología , Interferencia de ARN , Proteínas de Unión al ARN/genética , Espermidina/farmacología
3.
Int J Mol Sci ; 21(23)2020 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-33255323

RESUMEN

The translation of new therapies for spinal cord injury to clinical trials can be facilitated with large animal models close in morpho-physiological scale to humans. Here, we report functional restoration and morphological reorganization after spinal contusion in pigs, following a combined treatment of locomotor training facilitated with epidural electrical stimulation (EES) and cell-mediated triple gene therapy with umbilical cord blood mononuclear cells overexpressing recombinant vascular endothelial growth factor, glial-derived neurotrophic factor, and neural cell adhesion molecule. Preliminary results obtained on a small sample of pigs 2 months after spinal contusion revealed the difference in post-traumatic spinal cord outcomes in control and treated animals. In treated pigs, motor performance was enabled by EES and the corresponding morpho-functional changes in hind limb skeletal muscles were accompanied by the reorganization of the glial cell, the reaction of stress cell, and synaptic proteins. Our data demonstrate effects of combined EES-facilitated motor training and cell-mediated triple gene therapy after spinal contusion in large animals, informing a background for further animal studies and clinical translation.


Asunto(s)
Terapia por Estimulación Eléctrica , Factor Neurotrófico Derivado de la Línea Celular Glial/genética , Moléculas de Adhesión de Célula Nerviosa/genética , Traumatismos de la Médula Espinal/terapia , Factor A de Crecimiento Endotelial Vascular/genética , Adenoviridae/genética , Animales , Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Modelos Animales de Enfermedad , Espacio Epidural , Terapia Genética/métodos , Vectores Genéticos/uso terapéutico , Factor Neurotrófico Derivado de la Línea Celular Glial/uso terapéutico , Humanos , Actividad Motora/genética , Actividad Motora/fisiología , Moléculas de Adhesión de Célula Nerviosa/uso terapéutico , Neuroglía/trasplante , Recuperación de la Función/genética , Recuperación de la Función/efectos de la radiación , Médula Espinal/fisiopatología , Médula Espinal/efectos de la radiación , Traumatismos de la Médula Espinal/genética , Traumatismos de la Médula Espinal/fisiopatología , Porcinos/genética , Factor A de Crecimiento Endotelial Vascular/uso terapéutico
4.
Sci Signal ; 12(586)2019 06 18.
Artículo en Inglés | MEDLINE | ID: mdl-31213567

RESUMEN

Autosomal dominant mutations in GRIN2B are associated with severe encephalopathy, but little is known about the pathophysiological outcomes and any potential therapeutic interventions. Genetic studies have described the association between de novo mutations of genes encoding the subunits of the N-methyl-d-aspartate receptor (NMDAR) and severe neurological conditions. Here, we evaluated a missense mutation in GRIN2B, causing a proline-to-threonine switch (P553T) in the GluN2B subunit of NMDAR, which was found in a 5-year-old patient with Rett-like syndrome with severe encephalopathy. Structural molecular modeling predicted a reduced pore size of the mutant GluN2B-containing NMDARs. Electrophysiological recordings in a HEK-293T cell line expressing the mutated subunit confirmed this prediction and showed an associated reduced glutamate affinity. Moreover, GluN2B(P553T)-expressing primary murine hippocampal neurons showed decreased spine density, concomitant with reduced NMDA-evoked currents and impaired NMDAR-dependent insertion of the AMPA receptor subunit GluA1 at stimulated synapses. Furthermore, the naturally occurring coagonist d-serine restored function to GluN2B(P553T)-containing NMDARs. l-Serine dietary supplementation of the patient was hence initiated, resulting in the increased abundance of d-serine in the plasma and brain. The patient has shown notable improvements in motor and cognitive performance and communication after 11 and 17 months of l-serine dietary supplementation. Our data suggest that l-serine supplementation might ameliorate GRIN2B-related severe encephalopathy and other neurological conditions caused by glutamatergic signaling deficiency.


Asunto(s)
Encefalopatías , Suplementos Dietéticos , Mutación con Pérdida de Función , Receptores de N-Metil-D-Aspartato , Síndrome de Rett , Serina , Animales , Encefalopatías/tratamiento farmacológico , Encefalopatías/genética , Encefalopatías/metabolismo , Encefalopatías/patología , Niño , Cognición/efectos de los fármacos , Humanos , Masculino , Ratones , Modelos Moleculares , Actividad Motora/efectos de los fármacos , Actividad Motora/genética , N-Metilaspartato/farmacología , Receptores de N-Metil-D-Aspartato/química , Receptores de N-Metil-D-Aspartato/genética , Receptores de N-Metil-D-Aspartato/metabolismo , Síndrome de Rett/tratamiento farmacológico , Síndrome de Rett/genética , Síndrome de Rett/metabolismo , Síndrome de Rett/patología , Serina/administración & dosificación , Serina/farmacocinética
5.
Molecules ; 24(7)2019 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-30979037

RESUMEN

Humulus japonicus is an annual plant belonging to the Cannabacea family, and it has been traditionally used to treat pulmonary tuberculosis, dysentery, chronic colitis, and hypertension. We investigated the active components against Parkinson's disease from H. japonicus fraction (HJF) using high performance liquid chromatography (HPLC) coupled with quadruple-time-of-flight mass spectroscopy (qTOF-MS) and NMR. Fourteen compounds were isolated from HJF, including one new compound, using HPLC-qTOF-MS and NMR. The major compounds of HJF were luteolin-7-O-glucoside and apigenin-7-O-glucoside, and there was approximately 12.57- and 9.68-folds increase in the contents of these flavonoids compared to those of the 70% EtOH extract. Apigenin and luteolin exhibited the strongest inhibitory effects on monoamine oxidase (MAO) B enzyme activity. In animal studies, limb-use behavior was significantly reduced by unilateral 6-OHDA lesion and ipsilateral rotations. These results indicated that oral administration of 300 mg/kg HJF resulted in the improvement of motor asymmetry and motor impairment in unilateral 6-OHDA-lesioned mice. HJF, including active components leads to an improvement of motor behavior in a Parkinson's disease mouse model.


Asunto(s)
Humulus/química , Actividad Motora/efectos de los fármacos , Enfermedad de Parkinson Secundaria/tratamiento farmacológico , Extractos Vegetales/química , Administración Oral , Animales , Cromatografía Líquida de Alta Presión , Modelos Animales de Enfermedad , Flavonas/administración & dosificación , Flavonas/química , Regulación de la Expresión Génica/efectos de los fármacos , Glucósidos/administración & dosificación , Glucósidos/química , Humanos , Espectroscopía de Resonancia Magnética , Ratones , Monoaminooxidasa/genética , Actividad Motora/genética , Oxidopamina/toxicidad , Enfermedad de Parkinson Secundaria/inducido químicamente , Enfermedad de Parkinson Secundaria/genética , Enfermedad de Parkinson Secundaria/patología , Extractos Vegetales/administración & dosificación , Espectrometría de Masas en Tándem
6.
Physiol Behav ; 206: 213-224, 2019 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-31009639

RESUMEN

Capsaicin (CAP), the pungent ingredient of hot red pepper, is a selective ligand for the heat-sensitive transient receptor potential V1 cation channel 1 (TRPV1). Although CAP has been traditionally used as the ingredient of spices for various foods in the world, the effect of oral intake of CAP on thermoregulation and locomotor activity, and CAP-induced activation of brain neural circuits are not well understood. In this study, therefore, we examined the effects of oral gavage of CAP on core body and tail surface temperature, locomotor activity, and Fos expression in thermoregulation- and sensory information-associated hypothalamic and medullary brain regions using freely moving mice. Oral gavage of CAP acutely decreased core body temperature and alternatively increased tail surface temperature of wild type (WT) mice, whereas such acute temperature changes were not observed in TRPV1 knockout (KO) animals. Moreover, a long-lasting increase of locomotor activity was observed in both WT and TRPV1 KO mice after oral gavage of CAP, but increase in core body temperature was seen only in TRPV1 KO animals. Oral gavage of CAP induced neuronal Fos expression in the circumventricular organs, median and medial preoptic area, arcuate nucleus, and nucleus of the solitary tract, whereas neuronal Fos expression was scarcely observed in TRPV1 KO mice. Thus, the present study demonstrates in the mice that oral intake of CAP causes TRPV1-dependent acute hypothermia and TRPV1-independent long-lasting increase of locomotor activity, and moreover activates the brain circuits controlling thermoregulation and metabolism.


Asunto(s)
Regulación de la Temperatura Corporal/efectos de los fármacos , Temperatura Corporal/efectos de los fármacos , Capsaicina/farmacología , Hipotermia , Actividad Motora/efectos de los fármacos , Canales Catiónicos TRPV/genética , Animales , Hipotálamo/efectos de los fármacos , Hipotálamo/metabolismo , Ratones , Ratones Noqueados , Actividad Motora/genética , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Proteínas Proto-Oncogénicas c-fos/metabolismo , Canales Catiónicos TRPV/metabolismo
7.
Int J Dev Neurosci ; 72: 13-21, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30385192

RESUMEN

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by a core set of atypical behaviors in social-communicative and repetitive-motor domains. Individual profiles are widely heterogeneous and include language skills ranging from nonverbal to hyperlexic. The causal mechanisms underlying ASD remain poorly understood but appear to include a complex combination of polygenic and environmental risk factors. SHANK3 (SH3 and multiple ankyrin repeat domains 3) is one of a subset of well-replicated ASD-risk genes (i.e., genes demonstrating ASD associations in multiple studies), with haploinsufficiency of SHANK3 following deletion or de novo mutation seen in about 1% of non-syndromic ASD. SHANK3 is a synaptic scaffolding protein enriched in the postsynaptic density of excitatory synapses. In order to more closely evaluate the contribution of SHANK3 to neurodevelopmental expression of ASD, a knockout mouse model with a mutation in the PDZ domain was developed. Initial research showed compulsive/repetitive behaviors and impaired social interactions in these mice, replicating two core ASD features. The current study was designed to further examine Shank3B heterozygous and homozygous knockout mice for behaviors that might map onto atypical language in ASD (e.g., auditory processing, and learning/memory). We report findings of repetitive and atypical aggressive social behaviors (replicating prior reports), novel evidence that Shank3B KO mice have atypical auditory processing (low-level enhancements that might have a direct relationship with heightened pitch discrimination seen in ASD), as well as robust learning impairments.


Asunto(s)
Discapacidades para el Aprendizaje/complicaciones , Discapacidades para el Aprendizaje/genética , Mutación/genética , Proteínas del Tejido Nervioso/genética , Discriminación de la Altura Tonal/fisiología , Trastornos de la Sensación/etiología , Estimulación Acústica , Análisis de Varianza , Animales , Modelos Animales de Enfermedad , Conducta Exploratoria/fisiología , Hipocampo/patología , Discapacidades para el Aprendizaje/patología , Aprendizaje por Laberinto/fisiología , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Proteínas de Microfilamentos , Actividad Motora/genética , Proteínas del Tejido Nervioso/metabolismo , Reflejo de Sobresalto/genética , Prueba de Desempeño de Rotación con Aceleración Constante , Predominio Social
8.
Glia ; 66(12): 2589-2603, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30325069

RESUMEN

Gap junctions (GJs) coupling oligodendrocytes to astrocytes and to other oligodendrocytes are formed mainly by connexin47 (Cx47) and a smaller portion by connexin32 (Cx32). Mutations in both connexins cause inherited demyelinating disorders, but their expression is also disrupted in multiple sclerosis (MS). To clarify whether the loss of either Cx47 or Cx32 could modify the outcome of inflammation and myelin loss, we induced experimental autoimmune encephalomyelitis (EAE) in fully backcrossed Cx32 knockout (KO) and Cx47KO mice and compared their outcome with wild type (WT, C57BI/6 N) mice. Cx47KO EAE mice developed the most severe phenotype assessed by clinical scores and behavioral testing, followed by Cx32KO and WT mice. Cx47KO more than Cx32KO EAE mice developed more microglial activation, myelin, and axonal loss than did WT mice. Oligodendrocyte apoptosis and precursor proliferation was also higher in Cx47KO than in Cx32KO or WT EAE mice. Similarly, blood-spinal cord barrier (BSCB) disruption and inflammatory infiltrates of macrophages, T- and B-cells were more severe in Cx47KO than either Cx32KO or WT EAE groups. Finally, expression profiling revealed that several proinflammatory cytokines were higher at the peak of inflammation in the Cx47KO mice and persisted at later stages of EAE in contrast to reduction of their levels in WT EAE mice. Thus, loss of oligodendrocyte GJs aggravates BSCB disruption and inflammatory myelin loss, likely due to dysregulation of proinflammatory cytokines. This mechanism may play an important role in MS brain with reduced connexin expression, as well as in patients with inherited mutations in oligodendrocyte connexins and secondary inflammation.


Asunto(s)
Citocinas/metabolismo , Encefalomielitis Autoinmune Experimental/patología , Uniones Comunicantes/metabolismo , Regulación de la Expresión Génica/fisiología , Fuerza de la Mano/fisiología , Oligodendroglía/metabolismo , Animales , Apoptosis/genética , Astrocitos/metabolismo , Astrocitos/patología , Barrera Hematoencefálica/efectos de los fármacos , Barrera Hematoencefálica/fisiopatología , Proteínas de Unión al Calcio/metabolismo , Proliferación Celular/genética , Conexinas/genética , Conexinas/metabolismo , Modelos Animales de Enfermedad , Encefalomielitis Autoinmune Experimental/inducido químicamente , Encefalomielitis Autoinmune Experimental/genética , Encefalomielitis Autoinmune Experimental/fisiopatología , Adyuvante de Freund/toxicidad , Uniones Comunicantes/patología , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/genética , Macrófagos/patología , Ratones , Ratones Endogámicos C57BL , Proteínas de Microfilamentos/metabolismo , Actividad Motora/efectos de los fármacos , Actividad Motora/genética , Glicoproteína Mielina-Oligodendrócito/toxicidad , Oligodendroglía/patología , Fragmentos de Péptidos/toxicidad , Proteína beta1 de Unión Comunicante
9.
Nutrients ; 10(9)2018 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-30200401

RESUMEN

Aging is associated with motor disorders that decrease the quality of life (QOL). Royal jelly (RJ), used as a dietary supplement, has shown various health benefits and, therefore, it has the potential to improve the QOL during aging. We have previously developed protease enzyme-treated RJ to avoid the anaphylactic response induced by RJ supplementation. However, the effects of a lifelong treatment with RJ on normal aging have not been fully clarified. In this study, we investigated the effects of enzyme-untreated RJ (NRJ) and enzyme-treated RJ (ERJ) on the aging process focusing on motor functions, by using a genetically heterogeneous (HET) mouse model experimentally endowed with genetic diversity. We performed four different physical performance tests (grip strength, wire hang, horizontal bar, and rotarod). We showed that the age-related impairment of the motor functions was significantly delayed in RJ-treated mice. Both NRJ and ERJ were similarly effective against these types of aging-associated declines. Histological analyses revealed that the RJ treatment affected the muscle fiber size at an advanced age. We also demonstrated that age-related changes in muscle satellite cell markers and catabolic genes were affected in RJ-treated mice. These results suggest that non-protein components of RJ improved the motor function in aging mice. These findings indicate that RJ has the potential to change the QOL during aging by regulating the motor function.


Asunto(s)
Envejecimiento/efectos de los fármacos , Suplementos Dietéticos , Ácidos Grasos/farmacología , Heterogeneidad Genética , Actividad Motora/efectos de los fármacos , Destreza Motora/efectos de los fármacos , Músculo Esquelético/efectos de los fármacos , Factores de Edad , Envejecimiento/genética , Envejecimiento/metabolismo , Envejecimiento/patología , Animales , Regulación de la Expresión Génica/efectos de los fármacos , Longevidad/efectos de los fármacos , Masculino , Ratones Endogámicos BALB C , Ratones Endogámicos C3H , Ratones Endogámicos C57BL , Actividad Motora/genética , Fuerza Muscular/efectos de los fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Músculo Esquelético/fisiopatología , Atrofia Muscular/tratamiento farmacológico , Atrofia Muscular/metabolismo , Atrofia Muscular/patología , Atrofia Muscular/fisiopatología , Factores Sexuales
10.
Transl Psychiatry ; 7(12): 1269, 2017 12 08.
Artículo en Inglés | MEDLINE | ID: mdl-29217834

RESUMEN

Obesity and depression are major public health concerns, and there is increasing evidence that they share etiological mechanisms. CREB-regulated transcription coactivator 1 (CRTC1) participates in neurobiological pathways involved in both mood and energy balance regulation. Crtc1 -/- mice rapidly develop a depressive-like and obese phenotype in early adulthood, and are therefore a relevant animal model to explore possible common mechanisms underlying mood disorders and obesity. Here, the obese phenotype of male and female Crtc1 -/- mice was further characterized by investigating CRTC1's role in the homeostatic and hedonic regulation of food intake, as well as its influence on daily locomotor activity. Crtc1 -/- mice showed a strong gender difference in the homeostatic regulation of energy balance. Mutant males were hyperphagic and rapidly developed obesity on normal chow diet, whereas Crtc1 -/- females exhibited mild late-onset obesity without hyperphagia. Overeating of mutant males was accompanied by alterations in the expression of several orexigenic and anorexigenic hypothalamic genes, thus confirming a key role of CRTC1 in the central regulation of food intake. No alteration in preference and conditioned response for saccharine was observed in Crtc1 -/- mice, suggesting that mutant males' hyperphagia was not due to an altered hedonic regulation of food intake. Intriguingly, mutant males exhibited a hyperphagic behavior only during the resting (diurnal) phase of the light cycle. This abnormal feeding behavior was associated with a higher diurnal locomotor activity indicating that the lack of CRTC1 may affect circadian rhythmicity. Collectively, these findings highlight the male-specific involvement of CRTC1 in the central control of energy balance and circadian locomotor activity.


Asunto(s)
Ritmo Circadiano/fisiología , Depresión/fisiopatología , Metabolismo Energético/fisiología , Actividad Motora/fisiología , Factores de Transcripción/genética , Animales , Conducta Animal/fisiología , Ritmo Circadiano/genética , Depresión/genética , Modelos Animales de Enfermedad , Metabolismo Energético/genética , Femenino , Hiperfagia/genética , Hiperfagia/fisiopatología , Hipotálamo/metabolismo , Masculino , Ratones , Ratones Noqueados , Actividad Motora/genética , Obesidad/genética , Obesidad/fisiopatología , Factores Sexuales
11.
Proc Natl Acad Sci U S A ; 113(31): 8843-8, 2016 08 02.
Artículo en Inglés | MEDLINE | ID: mdl-27436896

RESUMEN

Disturbances in amino acid metabolism, which have been observed in Huntington's disease (HD), may account for the profound inanition of HD patients. HD is triggered by an expansion of polyglutamine repeats in the protein huntingtin (Htt), impacting diverse cellular processes, ranging from transcriptional regulation to cognitive and motor functions. We show here that the master regulator of amino acid homeostasis, activating transcription factor 4 (ATF4), is dysfunctional in HD because of oxidative stress contributed by aberrant cysteine biosynthesis and transport. Consistent with these observations, antioxidant supplementation reverses the disordered ATF4 response to nutrient stress. Our findings establish a molecular link between amino acid disposition and oxidative stress leading to cytotoxicity. This signaling cascade may be relevant to other diseases involving redox imbalance and deficits in amino acid metabolism.


Asunto(s)
Aminoácidos/metabolismo , Regulación de la Expresión Génica , Homeostasis/genética , Enfermedad de Huntington/genética , Factor de Transcripción Activador 4/genética , Factor de Transcripción Activador 4/metabolismo , Animales , Línea Celular , Células Cultivadas , Cistationina gamma-Liasa/deficiencia , Cistationina gamma-Liasa/genética , Cisteína/metabolismo , Humanos , Enfermedad de Huntington/metabolismo , Ratones Endogámicos C57BL , Ratones Noqueados , Actividad Motora/genética , Estrés Oxidativo
12.
Rev. int. med. cienc. act. fis. deporte ; 16(62): 297-315, jun. 2016. tab, graf
Artículo en Español | IBECS | ID: ibc-153358

RESUMEN

Estudios recientes observaron que las imágenes motrices se desarrollan de forma entrelazada con el desarrollo de las habilidades motrices en niños. La finalidad de este estudio es analizar en qué medida la imagen motriz de los elementos necesarios para resolver un problema motor (la recepción de un balón), se relaciona con los niveles de habilidad en niños (3 - 9 años). La muestra estuvo formada por 215 participantes (87 chicos y 118 chicas), (M = 5,94, DT = 1,47). Se ha utilizado una metodología mixta: dibujos, indicaciones gestuales, verbalización del pensamiento y una prueba práctica de recepción de balón. El MANOVA reveló diferencias significativas en las capacidades meta-cognitivas y motrices en función de las etapas de desarrollo. Un análisis de ecuaciones estructurales reveló que las capacidades meta-cognitivas median la relación entre las etapas de desarrollo y la habilidad de recepción de móviles. Se discuten sus repercusiones en el aprendizaje motor (AU)


Recent studies have found that motor imaginery is developed linked to the development of motor skills in children. The purpose of this study is to analyze how the motor imaginery of theprincipal elements to solve a motor problem (ball reception) relates to the motor skill levels in children (3-9 years). The sample consisted of 215 participants (87 boys and 118 girls), (M = 5.94, SD = 1.47).We used a mixed methodology: drawings, gestural prompts, verbalization of thought and a practical test of ball reception. The MANOVA revealed significant differences in the meta-cognitive abilities and motor function of the developmental stages. A structural equation analysis revealed that meta-cognitive abilities mediate the relationship between the stages of development and the ability in the reception of moving objects. Their implications in motor learning are discussed (AU)


Asunto(s)
Humanos , Masculino , Femenino , Niño , Destreza Motora/fisiología , Discapacidades para el Aprendizaje/metabolismo , Discapacidades para el Aprendizaje/psicología , Baloncesto/educación , Estudios Transversales/métodos , Actividad Motora/genética , Destreza Motora/clasificación , Discapacidades para el Aprendizaje/rehabilitación , Discapacidades para el Aprendizaje/terapia , Educación Primaria y Secundaria , Baloncesto/normas , Estudios Transversales , Actividad Motora/fisiología
13.
Sci Rep ; 6: 25564, 2016 05 05.
Artículo en Inglés | MEDLINE | ID: mdl-27146164

RESUMEN

Sleep deprivation (SD) leads to the spectrum of mood disorders like anxiety, cognitive dysfunctions and motor coordination impairment in many individuals. However, there is no effective pharmacological remedy to negate the effects of SD. The current study examined whether 50% ethanolic extract of Tinospora cordifolia (TCE) can attenuate these negative effects of SD. Three groups of adult Wistar female rats - (1) vehicle treated-sleep undisturbed (VUD), (2) vehicle treated-sleep deprived (VSD) and (3) TCE treated-sleep deprived (TSD) animals were tested behaviorally for cognitive functions, anxiety and motor coordination. TSD animals showed improved behavioral response in EPM and NOR tests for anxiety and cognitive functions, respectively as compared to VSD animals. TCE pretreatment modulated the stress induced-expression of plasticity markers PSA-NCAM, NCAM and GAP-43 along with proteins involved in the maintenance of LTP i.e., CamKII-α and calcineurin (CaN) in hippocampus and PC regions of the brain. Interestingly, contrary to VSD animals, TSD animals showed downregulated expression of inflammatory markers such as CD11b/c, MHC-1 and cytokines along with inhibition of apoptotic markers. This data suggests that TCE alone or in combination with other memory enhancing agents may help in managing sleep deprivation associated stress and improving cognitive functions.


Asunto(s)
Ansiedad/prevención & control , Cognición/efectos de los fármacos , Extractos Vegetales/farmacología , Privación de Sueño/prevención & control , Tinospora/química , Enfermedad Aguda , Animales , Apoptosis/efectos de los fármacos , Biomarcadores/metabolismo , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/patología , Etanol/química , Femenino , Aseo Animal/efectos de los fármacos , Mediadores de Inflamación/metabolismo , Aprendizaje por Laberinto/efectos de los fármacos , Actividad Motora/genética , Fitoterapia/métodos , Extractos Vegetales/química , Ratas Wistar , Privación de Sueño/fisiopatología , Privación de Sueño/psicología
14.
Neuropeptides ; 59: 97-109, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27080622

RESUMEN

Cocaine- and amphetamine-regulated transcript (CART) is a key neuropeptide with predominant expression in the hypothalamus central to the regulation of diverse biological processes, including food intake and energy expenditure. While there is considerable information on CART's role in the control of feeding, little is known about its thermoregulatory potential. Here we show the consequences of lack of CART signaling on major parameters of energy homeostasis in CART-/- mice under standard ambient housing (RT, 22°C), which is considered a mild cold exposure for mice, and thermoneutral conditions (TN, 30°C). WT mice kept at RT showed an increase in food intake, energy expenditure, BAT UCP-1 expression, and physical activity compared with TN condition, reflecting the augmented energy demand for thermogenesis at RT. On the molecular level, RT housing led to upregulated mRNA expression of TH, CRH, and TRH at the PVN, while NPY, AgRP and CART mRNA levels in the Arc were downregulated. CART-/- mice displayed elevated adiposity and diminished lean mass across both RT and TN. At RT, CART-/- mice showed unchanged food consumption yet greater body weight gain. In addition, an increase in energy expenditure and heightened BAT thermogenesis marked by UCP-1 protein expression was observed in the CART-/- mice. In contrast, TN-housed CART-/- mice exhibited lower weight gain than WT mice accompanied with pronounced reduction in basal feeding. These findings were correlated with reduced BAT temperature, but unchanged energy expenditure and UCP-1 levels. Interestingly, the respiratory exchange ratio for CART-/- mice, which shifted from lower at RT to higher at TN with respect to WT controls, indicates a transition of relative fuel source preference from fat to carbohydrate in the absence of CART signaling. Taken together, these results demonstrate that CART is a critical regulator of energy expenditure, energy partitioning and utilization dependent on the thermal environment.


Asunto(s)
Metabolismo Energético/genética , Homeostasis/genética , Hipotálamo/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Temperatura , Proteína Relacionada con Agouti/genética , Proteína Relacionada con Agouti/metabolismo , Animales , Composición Corporal/genética , Peso Corporal/genética , Hormona Liberadora de Corticotropina/genética , Hormona Liberadora de Corticotropina/metabolismo , Ingestión de Alimentos/genética , Femenino , Masculino , Ratones , Ratones Noqueados , Actividad Motora/genética , Proteínas del Tejido Nervioso/genética , Neuropéptido Y/genética , Neuropéptido Y/metabolismo , Proopiomelanocortina/genética , Proopiomelanocortina/metabolismo , Hormona Liberadora de Tirotropina/genética , Hormona Liberadora de Tirotropina/metabolismo
15.
J Neurosci ; 36(11): 3350-62, 2016 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-26985042

RESUMEN

The hypothalamo-pituitary-adrenocortical (HPA) axis regulates stress physiology and behavior. To achieve an optimally tuned adaptive response, it is critical that the magnitude of the stress response matches the severity of the threat. Corticotropin-releasing hormone (CRH) released from the paraventricular nucleus of the hypothalamus is a major regulator of the HPA axis. However, how CRH-producing neurons in an intact animal respond to different stressor intensities is currently not known. Using two-photon calcium imaging on intact larval zebrafish, we recorded the activity of CRH cells, while the larvae were exposed to stressors of varying intensity. By combining behavioral and physiological measures, we first determined how sudden alterations in environmental conditions lead to different levels of stress axis activation. Then, we measured changes in the frequency and amplitude of Ca(2+) transients in individual CRH neurons in response to such stressors. The response magnitude of individual CRH cells covaried with stressor intensity. Furthermore, stressors caused the recruitment of previously inactive CRH neurons in an intensity-dependent manner, thus increasing the pool of responsive CRH cells. Strikingly, stressor-induced activity appeared highly synchronized among CRH neurons, and also across hemispheres. Thus, the stressor strength-dependent output of CRH neurons emerges by a dual mechanism that involves both the increased activity of individual cells and the recruitment of a larger pool of responsive cells. The synchronicity of CRH neurons within and across hemispheres ensures that the overall output of the HPA axis matches the severity of the threat. SIGNIFICANCE STATEMENT: Stressors trigger adaptive responses in the body that are essential for survival. How the brain responds to acute stressors of varying intensity in an intact animal, however, is not well understood. We address this question using two-photon Ca(2+) imaging in larval zebrafish with transgenically labeled corticotropin-releasing hormone (CRH) cells, which represent a major regulator of the stress axis. We show that stressor strength-dependent responses of CRH neurons emerge via an intensity-dependent increase in the activity of individual CRH cells, and by an increase in the pool of responsive CRH cells at the population level. Furthermore, we report striking synchronicity among CRH neurons even across hemispheres, which suggests tight intrahypothalamic and interhypothalamic coordination. Thus, our work reveals how CRH neurons respond to different levels of acute stress in vivo.


Asunto(s)
Hormona Liberadora de Corticotropina/metabolismo , Regulación de la Expresión Génica/fisiología , Hipotálamo/patología , Potenciales de la Membrana/fisiología , Neuronas/fisiología , Estrés Fisiológico/fisiología , Animales , Animales Modificados Genéticamente , Reacción de Prevención/fisiología , Calcio/metabolismo , Hormona Liberadora de Corticotropina/genética , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Hidrocortisona/metabolismo , Larva , Proteínas Luminiscentes/genética , Proteínas Luminiscentes/metabolismo , Potenciales de la Membrana/genética , Actividad Motora/genética , Pez Cebra
16.
Neuron ; 89(4): 725-33, 2016 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-26833134

RESUMEN

Autism spectrum disorders (ASDs) are a group of devastating neurodevelopmental syndromes that affect up to 1 in 68 children. Despite advances in the identification of ASD risk genes, the mechanisms underlying ASDs remain unknown. Homozygous loss-of-function mutations in Contactin Associated Protein-like 2 (CNTNAP2) are strongly linked to ASDs. Here we investigate the function of Cntnap2 and undertake pharmacological screens to identify phenotypic suppressors. We find that zebrafish cntnap2 mutants display GABAergic deficits, particularly in the forebrain, and sensitivity to drug-induced seizures. High-throughput behavioral profiling identifies nighttime hyperactivity in cntnap2 mutants, while pharmacological testing reveals dysregulation of GABAergic and glutamatergic systems. Finally, we find that estrogen receptor agonists elicit a behavioral fingerprint anti-correlative to that of cntnap2 mutants and show that the phytoestrogen biochanin A specifically reverses the mutant behavioral phenotype. These results identify estrogenic compounds as phenotypic suppressors and illuminate novel pharmacological pathways with relevance to autism.


Asunto(s)
Trastorno Autístico/tratamiento farmacológico , Estrógenos/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/genética , Proteínas de la Membrana/genética , Mutación/genética , Proteínas del Tejido Nervioso/genética , Animales , Animales Modificados Genéticamente , Trastorno Autístico/genética , Modelos Animales de Enfermedad , Estrógenos/uso terapéutico , Genisteína/farmacología , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Humanos , Larva , Proteínas Luminiscentes/genética , Proteínas Luminiscentes/metabolismo , Actividad Motora/efectos de los fármacos , Actividad Motora/genética , Fenotipo , Fitoestrógenos/farmacología , Psicotrópicos/farmacología , Psicotrópicos/uso terapéutico , Convulsiones/tratamiento farmacológico , Convulsiones/genética , Trastornos de la Transición Sueño-Vigilia/tratamiento farmacológico , Trastornos de la Transición Sueño-Vigilia/genética , Proteína 2 de Transporte Vesicular de Glutamato/genética , Proteína 2 de Transporte Vesicular de Glutamato/metabolismo , Pez Cebra
17.
Exp Neurol ; 277: 68-75, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26710715

RESUMEN

Bis(monoacylglycero)phosphate (BMP) is a glycerophospholipid highly enriched in the lysosomal network and elevated in lysosomal diseases. To correct this elevation, BMP synthesis was manipulated by dietary fatty acid supplementation and the impact on subregional brain BMP and pathology assessed in the mouse model of mucopolysaccharidosis 1 (Hurler syndrome (HS)). There was widespread elevation of BMP in HS mice across all six sub-regions - brain stem, cortex, cerebellum, hippocampus, olfactory bulb and the sub-cortex - with 22:6/22:6 the most abundant species. Linoleic acid normalised total BMP in all regions except the cortex and cerebellum, although there were differences in fatty acid species; the major finding a decrease in 22:6- and a concomitant increase in 22:5-containing species. A battery of behaviour assessments showed that in the water cross maze both HS and wild type mice performed less well on the linoleic acid diet, and that both HS and wild type mice on the linoleic acid diet performed similarly and better in the exploratory open field test. This may be a consequence of differential subregional BMP composition in the brain. The effects of high fat and docosahexaenoic/eicosapentaenoic acid enriched diets were generally unremarkable. Although major pathologies were not completely abrogated, much of the neurobehavioural testing was confounded by skeletal pathology that did not resolve. This is the first detailed characterisation of subregional brain BMP species informing on the ability to manipulate this phospholipid in the brain, and as such, may hold promise as an adjunct therapy not only for HS but also for other lysosomal diseases.


Asunto(s)
Regulación de la Expresión Génica/genética , Iduronidasa/genética , Lisofosfolípidos/metabolismo , Monoglicéridos/metabolismo , Mucopolisacaridosis I/genética , Mucopolisacaridosis I/patología , Factores de Edad , Animales , Encéfalo/patología , Suplementos Dietéticos , Modelos Animales de Enfermedad , Femenino , Glicosaminoglicanos/orina , Iduronidasa/deficiencia , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Actividad Motora/genética , Mucopolisacaridosis I/dietoterapia , Mucopolisacaridosis I/fisiopatología , Factores Sexuales
18.
Enferm. nefrol ; 18(4): 273-281, oct.-dic. 2015. tab
Artículo en Español | IBECS | ID: ibc-147447

RESUMEN

Introducción: La capacidad funcional disminuida y la importante atrofia muscular caracterizan a los pacientes en hemodiálisis (HD). El ejercicio físico intradiálisis y recientemente la electroestimulación neuromuscular (EMS), representan dos serias opciones terapéuticas para mejorar esta deteriorada condición física. Actualmente, no existen estudios publicados sobre el papel de la EMS y la composición corporal en los pacientes en HD. Objetivo: Analizar que efecto produce un programa de EMS sobre la fuerza muscular, capacidad funcional, parámetros nutricionales y composición corporal en nuestros pacientes en HD. Material y Métodos: Estudio unicéntrico, prospectivo de 12 semanas de duración. Los pacientes incluidos realizaron un programa adaptativo de EMS en ambos cuádriceps intradiálisis mediante el dispositivo Compex R Theta 500i. Analizamos: 1.- Parámetros nutricionales (Albumina, pre albúmina, triglicéridos, colesterol total y fracciones, ferritina y Proteína C reactiva). 2.- Datos musculares: Composición muscular cuadriceps, Fuerza extensión máxima cuádriceps (FEMQ) y handgrip (HG) brazo dominante. 3.- Test funcionales: “Sit to stand to sit” (STS10) y “six- minutes walking test” (6MWT). 4.- Composición corporal mediante biompedancia electrica (BIA). Resultados: 13 pacientes incluidos: (69.2% hombres). Edad media: 65.7 años y 33.9 meses en HD. I.Charlson medio 9.1. La principal etiología de la ERC fue la DM ( 38.5%). Al final del estudio se observó una mejoría en (*p<0.05): FEMQ* ( 11.7±7.1 vs 13.4±7.4 Kg), STS10 (39.3±15.5 vs 35.8±13.7 seg), 6MWT* (9.9%, 293.2 vs 325.2 m). En relación a la composición corporal, se observó únicamente un aumento significativo del área muscular (AMQ*: 128.6 ± 30.2 vs 144.6 ± 22.4 cm2) y una disminución del área grasa (AGQ*: 76.5 ± 26.9 vs 62.1 ± 20.1 cm2) a nivel quadricipital, sin cambios en el resto de datos analizados (% grasa abdominal, peso graso, peso magro, agua corporal total). No se objetivaron cambios relevantes en los parámetros nutricionales y de adecuación dialítica. Conclusiones: 1.- La electroestimulación neuromuscular intradialísis mejoró la fuerza muscular, la capacidad funcional y la composición muscular del cuadriceps de nuestros pacientes en HD. 2.- Nuestros resultados remarcan el carácter local de la electroes-timulación neuromuscular, dada la ausencia de cambios relevantes en el resto de los parámetros nutricionales y datos corporales analizados. 3.- No obstante, son necesarios futuros estudios mejor diseñados, de cara a discernir si la electroestimulación neuromuscular podría ser una nueva alternativa terapéutica para evitar la atrofia muscular y el deterioro progresivo de la condición física de éstos pacientes (AU)


Background: The reduced functional capacity and significant muscle atrophy characterized patients on hemodialysis. Intradialytic exercise and recently neuromuscular electrostimulation (EMS) represent two serious therapeutical options to improve the deteriorated physical condition. Until date, there are no published studies about the role of EMS and body composition in HD patients. Objectives: Analyze the effect a program of EMS on muscle strength, functional capacity, nutritional parameters and body composition in our HD patients. Methods: A 12 weeks single-center, prospective study. Patients included in the study performed an intradialysis EMS adaptive program in both quadriceps using the Compex R Theta 500i device. We analyzed: 1.- Nutritional parameters (albumin, pre-albumin, triglycerides, total cholesterol and fractions, ferritin and C-reactive protein). 2.- Muscular data: Muscular composition, Maximum length quadriceps strength (MLQS) and “hand-grip” (HG) dominant arm. 3.- Functional capacity test: “Sit to stand to sit” (STS10) and “six- minutes walking test” (6MWT). 4.- Body composition. Results: 13 HD patients included: 69.2 % men. Mean age 65.7 years and 33.9 months on HD. A significant (* p < 0,05) improvement was observed in MLQS* (11.7±7.1 vs 13.4±7.4 Kg), STS10* (39.3±15.5 vs 35.8±13.7 seg), 6MWT* (9.9%, 293.2 vs 325.2 m). There was a signi-ficant increase in the quadriceps muscular area (QMA*: 128.6 ± 30.2 vs 144.6 ± 22.4 cm2) and decrease of fat quadricipital area (FQA*: 76.5 ± 26.9 vs 62.1 ± 20.1 cm2). No significant changes were observed in nutritional parameters, body composition (body fat percentage, lean and fat mass, total body water) or dialysis adecuacy data. Conclusions: 1.- Intradialysis quadriceps EMS improved muscle strength, functional capacity and the quadriceps muscle composition in our HD patients. 2.- Our results underline the local aspects on EMS, given the absence of relevant changes on nutritional parameters and body composition. 3.- Future studies are manadatory in order to establish if EMS could be a new alternative to prevent muscle atrophy and the progressive deterioration of the physical condition of these patients (AU)


Asunto(s)
Humanos , Masculino , Femenino , Estimulación Eléctrica Transcutánea del Nervio/instrumentación , Estimulación Eléctrica Transcutánea del Nervio/métodos , Fármacos Neuromusculares/administración & dosificación , Diálisis Renal/métodos , Actividad Motora/genética , Atrofia Muscular/complicaciones , Atrofia Muscular/metabolismo , Declaración de Helsinki , Músculo Cuádriceps/anomalías , Estimulación Eléctrica Transcutánea del Nervio/normas , Estimulación Eléctrica Transcutánea del Nervio , Fármacos Neuromusculares/metabolismo , Diálisis Renal/normas , Diálisis Renal , Actividad Motora/fisiología , Atrofia Muscular/sangre , Atrofia Muscular/diagnóstico , Músculo Cuádriceps/lesiones , Estudios Prospectivos
19.
J Neurosci ; 35(46): 15326-38, 2015 Nov 18.
Artículo en Inglés | MEDLINE | ID: mdl-26586820

RESUMEN

Selenium (Se) is essential for both brain development and male fertility. Male mice lacking two key genes involved in Se metabolism (Scly(-/-)Sepp1(-/-) mice), selenoprotein P (Sepp1) and Sec lyase (Scly), develop severe neurological dysfunction, neurodegeneration, and audiogenic seizures that manifest beginning in early adulthood. We demonstrate that prepubescent castration of Scly(-/-)Sepp1(-/-) mice prevents behavioral deficits, attenuates neurodegeneration, rescues maturation of GABAergic inhibition, and increases brain selenoprotein levels. Moreover, castration also yields similar neuroprotective benefits to Sepp1(-/-) and wild-type mice challenged with Se-deficient diets. Our data show that, under Se-compromised conditions, the brain and testes compete for Se utilization, with concomitant effects on neurodevelopment and neurodegeneration. SIGNIFICANCE STATEMENT: Selenium is an essential trace element that promotes male fertility and brain function. Herein, we report that prepubescent castration provides neuroprotection by increasing selenium-dependent antioxidant activity in the brain, revealing a competition between the brain and testes for selenium utilization. These findings provide novel insight into the interaction of sex and oxidative stress upon the developing brain and have potentially significant implications for the prevention of neurodevelopmental disorders characterized by aberrant excitatory/inhibitory balance, such as schizophrenia and epilepsy.


Asunto(s)
Encéfalo/metabolismo , Liasas/metabolismo , Trastornos del Neurodesarrollo/genética , Selenio/metabolismo , Selenoproteína P/metabolismo , Factores de Edad , Animales , Encéfalo/efectos de los fármacos , Encéfalo/patología , Castración , Maleato de Dizocilpina/farmacología , Epilepsia Refleja/genética , Conducta Exploratoria/efectos de los fármacos , Conducta Exploratoria/fisiología , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/genética , Glutamato Descarboxilasa/metabolismo , Liasas/genética , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Aprendizaje por Laberinto/fisiología , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Actividad Motora/efectos de los fármacos , Actividad Motora/genética , Proteínas del Tejido Nervioso/metabolismo , Trastornos del Neurodesarrollo/metabolismo , Trastornos del Neurodesarrollo/patología , Trastornos del Neurodesarrollo/prevención & control , Selenoproteína P/genética , Factores Sexuales , Factores de Transcripción/metabolismo
20.
J Neuroinflammation ; 12: 103, 2015 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-26016857

RESUMEN

BACKGROUND: The acupuncture or electroacupuncture (EA) shows the therapeutic effect on various neurodegenerative diseases. This effect was thought to be partially achieved by its ability to alleviate existing neuroinflammation and glial dysfunction. In this study, we systematically investigated the effect of EA on abnormal neurochemical changes and motor symptoms in a mouse neurodegenerative disease model. METHODS: The transgenic mouse which expresses a mutant α-synuclein (α-syn) protein, A53T α-syn, in brain astrocytic cells was used. These mice exhibit extensive neuroinflammatory and motor phenotypes of neurodegenerative disorders. In this study, the effects of EA on these phenotypic changes were examined in these mice. RESULTS: EA improved the movement detected in multiple motor tests in A53T mutant mice. At the cellular level, EA significantly reduced the activation of microglia and prevented the loss of dopaminergic neurons in the midbrain and motor neurons in the spinal cord. At the molecular level, EA suppressed the abnormal elevation of proinflammatory factors (tumor necrosis factor-α and interleukin-1ß) in the striatum and midbrain of A53T mice. In contrast, EA increased striatal and midbrain expression of a transcription factor, nuclear factor E2-related factor 2, and its downstream antioxidants (heme oxygenase-1 and glutamate-cysteine ligase modifier subunits). CONCLUSIONS: These results suggest that EA possesses the ability to ameliorate mutant α-syn-induced motor abnormalities. This ability may be due to that EA enhances both anti-inflammatory and antioxidant activities and suppresses aberrant glial activation in the diseased sites of brains.


Asunto(s)
Astrocitos/metabolismo , Electroacupuntura/métodos , Mutación/genética , Enfermedades Neurodegenerativas , alfa-Sinucleína/genética , Animales , Proteínas de Unión al Calcio/metabolismo , Conducta Exploratoria/fisiología , Trastornos Neurológicos de la Marcha/etiología , Trastornos Neurológicos de la Marcha/terapia , Regulación de la Expresión Génica/efectos de los fármacos , Regulación de la Expresión Génica/genética , Proteína Ácida Fibrilar de la Glía/genética , Proteína Ácida Fibrilar de la Glía/metabolismo , Glutamato-Cisteína Ligasa/genética , Glutamato-Cisteína Ligasa/metabolismo , Hemo-Oxigenasa 1/genética , Hemo-Oxigenasa 1/metabolismo , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Ratones , Ratones Transgénicos , Proteínas de Microfilamentos/metabolismo , Actividad Motora/efectos de los fármacos , Actividad Motora/genética , Neuronas Motoras/efectos de los fármacos , Neuronas Motoras/metabolismo , Neuronas Motoras/patología , Fuerza Muscular/genética , Fuerza Muscular/fisiología , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Enfermedades Neurodegenerativas/genética , Enfermedades Neurodegenerativas/patología , Enfermedades Neurodegenerativas/terapia , Médula Espinal/patología
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