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1.
Int J Mol Sci ; 21(7)2020 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-32260050

RESUMEN

Autophagy is an essential mechanism to maintain cellular homeostasis. Besides its role in controlling the quality of cytoplasmic components, it participates in nutrient obtaining and lipid mobilization under stressful conditions. Furthermore, autophagy is involved in the regulation of systemic metabolism as its blockade in hypothalamic neurons can affect the central regulation of metabolism and impact body energy balance. Moreover, hypothalamic autophagy can be altered during obesity, one of the main alterations of metabolism nowadays. In this review, we focus on the role of astrocytes, essential cells for brain homeostasis, which represent key metabolic regulators. Astrocytes can sense metabolic signals in the hypothalamus and modulate systemic functions as glucose homeostasis and feeding response. Moreover, the response of astrocytes to obesity has been widely studied. Astrocytes are important mediators of brain inflammation and can be affected by increased levels of saturated fatty acids associated with obesity. Although autophagy plays important roles for astrocyte homeostasis and functioning, the contribution of astrocyte autophagy to systemic metabolism has not been analyzed yet. Furthermore, how obesity can impact astrocyte autophagy is poorly understood. More studies are needed in order to understand the contribution of astrocyte autophagy to metabolism.


Asunto(s)
Astrocitos/fisiología , Autofagia , Metabolismo Energético , Hipotálamo/metabolismo , Obesidad/metabolismo , Animales , Astrocitos/citología , Ácidos Grasos/metabolismo , Homeostasis , Humanos , Hipotálamo/citología
2.
Healthcare (Basel) ; 10(1)2021 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-35052235

RESUMEN

The consumption of cannabis and alcohol results in a variety of effects on the psychic functions of young users. Notwithstanding their widespread and prevalent use, the impact of these drugs on sexual health remains unknown. Thus, the aim of this study is to analyse the influence of alcohol and cannabis consumption on sexual function in young people. An observational study was conducted in 274 participants aged 18-30 years. The following selection tools were used: Alcohol Use Disorders Identification Test, Cannabis Abuse Screening Test (CAST), and Changes in Sexual Functioning Questionnaire Short-Form. Participants who were at high risk of having cannabis-related problems performed better on the CAST concerning sexual function, arousal, and orgasm. Participants at high risk had higher arousal and orgasm scores than those who were not at risk for cannabis problems. Improvements in sexual function were found between people who were at high risk of having alcohol problems and those who were not at risk. Sexual function in young people who use cannabis and alcohol more frequently was shown to be better than in those who do not use either, highlighting the need for more information aimed at the young population.

3.
J Neuroendocrinol ; 32(1): e12774, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31323169

RESUMEN

Cardiolipin (CL) is a phospholipid that is almost exclusively located in the inner mitochondrial membrane of eukaryotic cells. As a result of its unique structure and distribution, CL establishes non-covalent bonds with a long list of proteins involved in ATP production, mitochondria biogenesis, mitophagy and apoptosis. Thus, the amount of CL, as well as its fatty acid composition and location, strongly impacts upon mitochondrial-dependent functions and therefore the metabolic homeostasis of different tissues. The brain is particularly sensitive to mitochondrial dysfunction as a result of its high metabolic demand. Several mitochondrial related-neurodegenerative disorders, as well as physiological ageing, show altered CL metabolism. Furthermore, mice lacking enzymes involved in CL synthesis show cognitive impairments. CL content and metabolism are regulated by gonadal hormones in the developing and adult brain. In neuronal cultures, oestradiol increases CL content, whereas adult ovariectomy decreases CL content and alters CL metabolism in the hippocampal mitochondria. Transient sex differences in brain CL metabolism have been detected during development. At birth, brain CL has a higher proportion of unsaturated fatty acids in the brain of male mice than in the brain of females. In addition, the expression of enzymes involved in CL de novo and recycling synthetic pathways is higher in males. Most of these sex differences are abolished by the neonatal androgenisation of females, suggesting a role for testosterone in the generation of sex differences in brain CL. The regulation of brain CL by gonadal hormones may be linked to their homeostatic and protective actions in neural cells, as well as the manifestation of sex differences in neurodegenerative disorders.


Asunto(s)
Encéfalo/metabolismo , Cardiolipinas/metabolismo , Hormonas Esteroides Gonadales/metabolismo , Neuronas/metabolismo , Animales , Femenino , Humanos , Masculino , Mitocondrias/metabolismo , Caracteres Sexuales
4.
Mol Neurobiol ; 56(3): 1665-1680, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29916142

RESUMEN

Obesity is associated with an increase in the brain levels of saturated free fatty acids, such as palmitic acid (PA). Previous studies have shown that PA exerts proinflammatory actions and reduces cell viability in astrocyte cultures. In this study, we have assessed whether an alteration in autophagy is involved in the effects of PA on astrocytes. Primary astrocytes were obtained from the cerebral cortex of male and female CD1 mouse pups and were incubated for 4.5 or 24 h with 250-500 µM PA. PA increased the levels of LC3-II, an autophagosome marker, and reduced LC3-II flux in astrocytes, suggesting a blockade of autophagy. This effect was observed both after 4.5 and 24 h of treatment with PA. PA had additional effects after treatment for 24 h, increasing the expression of proinflammatory cytokines, decreasing cell viability, and increasing the levels of an endoplasmic reticulum stress marker. In addition, PA decreased the expression of estrogen receptors, but only in female astrocytes. However, the treatment with estradiol, estrogen receptor agonists, or inhibitor of estradiol synthesis did not counteract the action of PA on cell viability. Rapamycin, an autophagy inducer, was unable to prevent the effect of PA on cell viability. In addition, hydroxychloroquine, an autophagy blocker, did not cause per se astrocyte death. These findings suggest that the effect of PA on autophagy is not sufficient to induce astrocyte loss, which is only observed when prolonged PA treatment causes other alterations in astrocytes, such as increased inflammation and endoplasmic reticulum stress.


Asunto(s)
Astrocitos/efectos de los fármacos , Autofagia/efectos de los fármacos , Corteza Cerebral/efectos de los fármacos , Ácido Palmítico/farmacología , Animales , Astrocitos/citología , Astrocitos/metabolismo , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Corteza Cerebral/citología , Corteza Cerebral/metabolismo , Estrés del Retículo Endoplásmico/efectos de los fármacos , Estradiol/farmacología , Femenino , Masculino , Ratones , Caracteres Sexuales , Sirolimus/farmacología
5.
Cell Death Discov ; 5: 85, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30962951

RESUMEN

In the nervous system, Notch pathway has a prominent role in the control of neuronal morphology and in the determination of the astrocyte fate. However, the role of Notch in morphological astrocyte plasticity is unknown. Here, we have explored the role of Notch activity on the morphological reactivity of primary astrocytes in response to LPS, an inflammatory stimulus. We found that LPS induces reactive astrocyte morphology by the inhibition of Notch signaling via NFκB activation and Jagged upregulation. In contrast, IGF-1, an anti-inflammatory molecule, inhibits LPS-induced reactive astrocyte morphological phenotype by enhancing Notch signaling through the inhibition of NFκB and the activation of MAPK. Therefore, Notch signaling pathway emerges as a mediator of the regulation of astrocyte morphology by inflammatory and anti-inflammatory stimuli.

6.
Rev Peru Med Exp Salud Publica ; 35(2): 333-337, 2018.
Artículo en Español | MEDLINE | ID: mdl-30183926

RESUMEN

We present a case of mastitis in a 45-year-old woman with no history of infection in other areas of the body, with unspecific clinical picture, imaging studies, and bacilloscopy. However, histological samples obtained by aspiration showed giant epithelial cells, necrosis, and granulomatous formations, which justified a clinical inclination toward tuberculosis. In the absence of confirmatory evidence of any lesions in other tissues, the existence of mastitis of torpid evolution is a clinical indication to suspect mammary tuberculosis, since the characteristics of the process usually lead to erroneous diagnoses with other breast tumors such as cancer. Tuberculosis in the breast is a rare disease with a difficult diagnosis due to the low clinical and microbiological evidence and the lack of specificity of the imaging results, so the suspicion of its real diagnostic possibility is a fundamental condition for its determination, even when the causal agent is not confirmed.


Presentamos caso de mastitis en mujer de 45 años sin antecedentes de infección en otras regiones corporales. Presentó cuadro clínico, estudios de imágenes y baciloscopia inespecíficos, sin embargo, mediante muestras histológicas obtenidas por punción aspirativa se encontró células epiteliodes gigantes, necrosis y formaciones granulomatosas, lo cual justificó el pensamiento clínico en tuberculosis. En ausencia de evidencias confirmatorias de lesión en otros tejidos, la existencia de mastitis de evolución tórpida es un indicativo clínico para sospechar tuberculosis mamaria, pues usualmente las características del proceso suelen plantear diagnósticos erróneos con otras entidades tumorales de la mama como cáncer. La tuberculosis en mama, representa una rara enfermedad cuyo diagnóstico es difícil por las bajas evidencias clínicas, microbiológicas y la inespecificidad de los resultados imagenológicos, por lo que la sospecha de su real posibilidad diagnóstica es una condición primordial para su determinación, aun cuando no se confirme el agente causal.


Asunto(s)
Mastitis/microbiología , Tuberculosis , Femenino , Humanos , Mastitis/diagnóstico , Mastitis/tratamiento farmacológico , Persona de Mediana Edad , Tuberculosis/diagnóstico , Tuberculosis/tratamiento farmacológico
7.
Sci Rep ; 7: 43878, 2017 03 06.
Artículo en Inglés | MEDLINE | ID: mdl-28262723

RESUMEN

Cardiolipin (CL) is a mitochondrial-specific phospholipid. CL content and acyl chain composition are crucial for energy production. Given that estradiol induces CL synthesis in neurons, we aimed to assess CL metabolism in the cerebral cortex (CC) of male and female mice during early postnatal life, when sex steroids induce sex-dimorphic maturation of the brain. Despite the fact that total amount of CL was similar, its fatty acid composition differed between males and females at birth. In males, CL was more mature (lower saturation ratio) and the expression of the enzymes involved in synthetic and remodeling pathways was higher, compared to females. Importantly, the sex differences found in CL metabolism were due to the testosterone peak that male mice experience perinatally. These changes were associated with a higher expression of UCP-2 and its activators in the CC of males. Overall, our results suggest that the perinatal testosterone surge in male mice regulates CL biosynthesis and remodeling in the CC, inducing a sex-dimorphic fatty acid composition. In male's CC, CL is more susceptible to peroxidation, likely explaining the testosterone-dependent induction of neuroprotective molecules such as UCP-2. These differences may account for the sex-dependent mitochondrial susceptibility after perinatal hypoxia/ischemia.


Asunto(s)
Cardiolipinas/metabolismo , Corteza Cerebral/metabolismo , Mitocondrias/metabolismo , Testosterona/metabolismo , Animales , Animales Recién Nacidos , Corteza Cerebral/crecimiento & desarrollo , Ácidos Grasos/metabolismo , Femenino , Regulación del Desarrollo de la Expresión Génica , Masculino , Ratones Endogámicos C57BL , Factores Sexuales , Factores de Tiempo , Proteína Desacopladora 2/genética , Proteína Desacopladora 2/metabolismo
8.
Sci Rep ; 6: 31891, 2016 08 24.
Artículo en Inglés | MEDLINE | ID: mdl-27553191

RESUMEN

Testosterone produced by the foetal testis is converted by male neurons to oestradiol, which masculinizes neuronal morphology. Female neurons are known to synthesize oestradiol in absence of exogenous testosterone. However, the role of neuronal oestradiol on the differentiation of foetal female neurons is unknown. Here we show that, due to endogenous neuronal oestradiol synthesis, female hippocampal neurons have higher expression of the neuritogenic protein Neurogenin 3 and enhanced neuritogenesis than males. Exogenous application of testosterone or its metabolite dihydrotestosterone increases Neurogenin 3 expression and promotes neuritogenesis in males, but reduces these parameters in females. Together our data indicate that gonadal-independent oestradiol synthesis by female neurons participates in the generation of sex differences in hippocampal neuronal development.


Asunto(s)
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Estradiol/metabolismo , Hipocampo/embriología , Proteínas del Tejido Nervioso/metabolismo , Neuritas/metabolismo , Neuronas/citología , Caracteres Sexuales , Animales , Diferenciación Celular , Células Cultivadas , Embrión de Mamíferos/citología , Embrión de Mamíferos/metabolismo , Femenino , Hipocampo/citología , Hipocampo/metabolismo , Humanos , Masculino , Ratones , Neuronas/metabolismo
9.
Brain Res ; 1644: 176-82, 2016 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-27174000

RESUMEN

Dehydroepiandrosterone (DHEA) modulates neurogenesis, neuronal function, neuronal survival and metabolism, enhancing mitochondrial oxidative capacity. Glucose deprivation and hypometabolism have been implicated in the mechanisms that mediate neuronal damage in neurological disorders, and some studies have shown that these mechanisms are sexually dimorphic. It was also demonstrated that DHEA is able to attenuate the hypometabolism that is related to some neurodegenerative diseases, eliciting neuroprotective effects in different experimental models of neurodegeneration. The aim of this study was to evaluate the effect of DHEA on the viability of male and female hippocampal neurons and SH-SY5Y neuroblastoma cells exposed to glucose deprivation. It was observed that after 12h of pre-treatment, DHEA was able to protect SH-SY5Y cells from glucose deprivation for 6h (DHEA 10(-12), 10(-8) and 10(-6)M) and 8h (DHEA 10(-8)M). In contrast, DHEA was not neuroprotective against glucose deprivation for 12 or 24h. DHEA (10(-8)M) also protected SH-SY5Y cells when added together or even 1h after the beginning of glucose deprivation (6h). Furthermore, DHEA (10(-8)M) also protected primary neurons from both sexes against glucose deprivation. In summary, our findings indicate that DHEA is neuroprotective against glucose deprivation in human neuroblastoma cells and in male and female mouse hippocampal neurons. These results suggest that DHEA could be a promising candidate to be used in clinical studies aiming to reduce neuronal damage in people from both sexes.


Asunto(s)
Deshidroepiandrosterona/farmacología , Hipocampo/efectos de los fármacos , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Animales , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Femenino , Glucosa/metabolismo , Hipocampo/metabolismo , Humanos , Masculino , Ratones , Neuronas/metabolismo , Cultivo Primario de Células
10.
Rev. peru. med. exp. salud publica ; 35(2): 333-337, abr.-jun. 2018. graf
Artículo en Español | LILACS | ID: biblio-961869

RESUMEN

RESUMEN Presentamos caso de mastitis en mujer de 45 años sin antecedentes de infección en otras regiones corporales. Presentó cuadro clínico, estudios de imágenes y baciloscopia inespecíficos, sin embargo, mediante muestras histológicas obtenidas por punción aspirativa se encontró células epiteliodes gigantes, necrosis y formaciones granulomatosas, lo cual justificó el pensamiento clínico en tuberculosis. En ausencia de evidencias confirmatorias de lesión en otros tejidos, la existencia de mastitis de evolución tórpida es un indicativo clínico para sospechar tuberculosis mamaria, pues usualmente las características del proceso suelen plantear diagnósticos erróneos con otras entidades tumorales de la mama como cáncer. La tuberculosis en mama, representa una rara enfermedad cuyo diagnóstico es difícil por las bajas evidencias clínicas, microbiológicas y la inespecificidad de los resultados imagenológicos, por lo que la sospecha de su real posibilidad diagnóstica es una condición primordial para su determinación, aun cuando no se confirme el agente causal.


ABSTRACT We present a case of mastitis in a 45-year-old woman with no history of infection in other areas of the body, with unspecific clinical picture, imaging studies, and bacilloscopy. However, histological samples obtained by aspiration showed giant epithelial cells, necrosis, and granulomatous formations, which justified a clinical inclination toward tuberculosis. In the absence of confirmatory evidence of any lesions in other tissues, the existence of mastitis of torpid evolution is a clinical indication to suspect mammary tuberculosis, since the characteristics of the process usually lead to erroneous diagnoses with other breast tumors such as cancer. Tuberculosis in the breast is a rare disease with a difficult diagnosis due to the low clinical and microbiological evidence and the lack of specificity of the imaging results, so the suspicion of its real diagnostic possibility is a fundamental condition for its determination, even when the causal agent is not confirmed.


Asunto(s)
Femenino , Humanos , Persona de Mediana Edad , Tuberculosis , Mastitis/microbiología , Tuberculosis/diagnóstico , Tuberculosis/tratamiento farmacológico , Mastitis/diagnóstico , Mastitis/tratamiento farmacológico
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