RESUMEN
Depression is a prominent complex psychiatric disorder, usually complicated through expression of comorbid conditions, with chronic pain being among the most prevalent. This comorbidity is consistently associated with a poor prognosis and has been shown to negatively impact patient outcomes. With a global rise in this condition presenting itself, the importance of discovering long-term, effective, and affordable treatments is crucial. Electroacupuncture has demonstrated renowned success in its use for the treatment of pain and is a widely recognized therapy in clinical practice for the treatment of various psychosomatic disorders, most notably depression. Our study aimed to investigate the effects and mechanisms of Acid-Saline (AS) inducing states of chronic pain and depression comorbidity in the cerebellum, using the ST36 acupoint as the therapeutic intervention. Furthermore, the role of TRPV1 was relatedly explored through the use of TRPV1-/- mice (KO). The results indicated significant differences in the four behavioral tests used to characterize pain and depression states in mice. The AS and AS + SHAM group showed significant differences when compared to the Control and AS + EA groups in the von Frey and Hargreaves's tests, as well as the Open-Field and Forced Swimming tests. This evidence was further substantiated in the protein levels observed in immunoblotting, with significant differences between the AS and AS + SHAM groups when compared to the AS + EA and AS + KO groups being identified. In addition, immunofluorescence visibly served to corroborate the quantitative outcomes. Conclusively these findings suggest that AS-induced chronic pain and depression comorbidity elicits changes in the cerebellum lobules VI, VII, VIII, which are ameliorated through the use of EA at ST36 via its action on TRPV1 and related molecular pathways. The action of TRPV1 is not singular in CPDC, which would suggest other potential targets such as acid-sensing ion channel subtype 3 (ASIC3) or voltage-gated sodium channels (Navs) that could be explored in future studies.
Asunto(s)
Canales Iónicos Sensibles al Ácido/genética , Dolor Crónico/genética , Depresión/genética , Canales Catiónicos TRPV/genética , Ácidos/toxicidad , Puntos de Acupuntura , Animales , Cerebelo/metabolismo , Cerebelo/patología , Cerebelo/efectos de la radiación , Dolor Crónico/inducido químicamente , Dolor Crónico/complicaciones , Dolor Crónico/terapia , Comorbilidad , Depresión/complicaciones , Depresión/patología , Modelos Animales de Enfermedad , Electroacupuntura , Humanos , Ratones , Ratones Noqueados , Solución Salina/toxicidad , NataciónRESUMEN
Non-invasive brain stimulation techniques including repetitive transcranial magnetic stimulation (rTMS), continuous theta-burst stimulation (cTBS), paired associative stimulation (PAS), and transcranial direct current stimulation (tDCS) have been applied over the cerebellum to induce plasticity and gain insights into the interaction of the cerebellum with neo-cortical structures including the motor cortex. We compared the effects of 1 Hz rTMS, cTBS, PAS and tDCS given over the cerebellum on motor cortical excitability and interactions between the cerebellum and dorsal premotor cortex / primary motor cortex in two within subject designs in healthy controls. In experiment 1, rTMS, cTBS, PAS, and tDCS were applied over the cerebellum in 20 healthy subjects. In experiment 2, rTMS and PAS were compared to sham conditions in another group of 20 healthy subjects. In experiment 1, PAS reduced cortical excitability determined by motor evoked potentials (MEP) amplitudes, whereas rTMS increased motor thresholds and facilitated dorsal premotor-motor and cerebellum-motor cortex interactions. TDCS and cTBS had no significant effects. In experiment 2, MEP amplitudes increased after rTMS and motor thresholds following PAS. Analysis of all participants who received rTMS and PAS showed that MEP amplitudes were reduced after PAS and increased following rTMS. rTMS also caused facilitation of dorsal premotor-motor cortex and cerebellum-motor cortex interactions. In summary, cerebellar 1 Hz rTMS and PAS can effectively induce plasticity in cerebello-(premotor)-motor pathways provided larger samples are studied.
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Potenciales Evocados Motores/fisiología , Corteza Motora/fisiología , Estimulación Transcraneal de Corriente Directa , Estimulación Magnética Transcraneal , Adulto , Cerebelo/diagnóstico por imagen , Cerebelo/fisiología , Cerebelo/efectos de la radiación , Potenciales Evocados Motores/efectos de la radiación , Femenino , Humanos , Masculino , Corteza Motora/diagnóstico por imagen , Corteza Motora/efectos de la radiación , Inhibición Neural/efectos de la radiación , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/fisiología , Vías Nerviosas/efectos de la radiaciónRESUMEN
PURPOSE: The present study aims to investigate the radioprotective effect of melatonin (MEL) against early period brain damage caused by different dose rate beams in the experimental rat model. MATERIALS AND METHODS: Forty-eight Sprague Dawley rats were randomly divided into six groups; the control, only melatonin, low dose rate-radiotherapy (LDR-RT), high dose rate-radiotherapy (HDR-RT) groups and (LDR-RT) + MEL and (HDR-RT) + MEL radiotherapy plus melatonin groups. Each rat administered melatonin was given a dose of 10 mg/kg through intraperitoneal injection, 15 minutes before radiation exposure. The head and neck region of each rat in only radiotherapy and radiotherapy plus melatonin groups was irradiated with a single dose of 16 Gy in LDR-RT and HDR-RT beams. Rats in all groups were examined for histopathology and biochemistry analysis 10 days after radiotherapy. RESULTS: Comparing the findings for LDR-RT and HDR-RT only radiotherapy groups and the control group, there was a statistically significant difference in histopathological and biochemical parameters, however, melatonin administered in radiotherapy plus melatonin groups contributed improving these parameters (p < .05). There was no statistically significant difference between LDR-RT and HDR-RT beams (p > .05). CONCLUSIONS: It was concluded that melatonin applied before LDR-RT and HDR-RT radiotherapy protected early period radiotherapy-induced brain damage. The effects of clinically low and high dose beams on the cerebral cortex and cerebellum were investigated histopathologically for the first time. HDR beams can be safely applied in brain radiotherapy. However, more experimental rat and clinical studies are needed to explain the radiobiological uncertainties about the clinic dose rate on different cancerous and healthy tissues.
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Cerebelo/efectos de la radiación , Corteza Cerebral/efectos de la radiación , Melatonina/farmacología , Protectores contra Radiación/farmacología , Radioterapia/efectos adversos , Animales , Cerebelo/patología , Corteza Cerebral/patología , Femenino , Dosificación Radioterapéutica , Ratas , Ratas Sprague-DawleyRESUMEN
The adverse health consequences of exposure to electromagnetic field emitted from cell phone has recently raised public concerns worldwide. Also, the Global System for Mobile Communications (GSM) standard that operates in 900 MHz frequency is the most popular. Therefore, we aimed to investigate the adverse effect of exposure to 900 MHz EMF (1 h/day) on the cerebella of 12-week-old rats. We also evaluated the protective activity of luteolin (20 µg/kg/day) against possible biological change in the cerebellar tissues exposed to EMF. Twenty-four male wistar albino rats were randomly assigned into four group of six rats: Control, EMF, EMF + luteolin, luteolin. Serological and biochemical analyses, as well as histopathological examination were performed on all cerebellar samples. We found that SOD (superoxide dismutase) level was significantly increased in the EMF group compared to the control group (p < 0.05). To the contrary, decreased SOD activity was detected in the EMF + luteolin group compared to control group (p < 0.05). The total number of Purkinje and granular cells was significantly decreased in the EMF group compared to the control group (p < 0.05). In the EMF + luteolin group, the total number of Purkinje and granular cells was significantly higher than the EMF group (p < 0.05). Histopathological evaluation also showed destructive damage to the architectures of cerebellar tissues. Our results suggest that exposure to EMF may cause cellular damage to the rat cerebellum. Further, the improvement of cerebellar damage may have resulted from antioxidant efficacy of luteolin by alleviating oxidative stress.
Asunto(s)
Cerebelo/efectos de los fármacos , Campos Electromagnéticos/efectos adversos , Radiación Electromagnética , Luteolina/farmacología , Fármacos Neuroprotectores/farmacología , Animales , Cerebelo/patología , Cerebelo/efectos de la radiación , Masculino , Ratas , Ratas Wistar , Superóxido Dismutasa/efectos de la radiaciónRESUMEN
OBJECTIVE: To evaluate the effects of prenatal radiation of 850ï½1 900 MHz mobile phone on white matter in cerebellum of adult rat offspring. METHODS: Pregnant rats were randomly divided into short term maternal radiation group, long term maternal radiation group and control group. Rats in short term and long term maternal radiation group were exposed to 6 h/d and 24 h/d mobile phone radiation during 1-17 days of pregnancy, respectively. The cerebellums of offspring rats at the age of 3 month(nï¼8)were taken. Cell morphology in cerebellum was studied by hematoxylin-eosin (HE) staining. The expressions of myelin basic protein (MBP), neurofilament-L (NF-L) and glial fibrillary acidic protein (GFAP) in cerebellum of rat offspring were detected by immunohistochemistry and Western blot. RESULTS: Compared to control group, the morphological changes of purkinje cells in cerebellum were obvious in rat offspring of short term and long term maternal radiation group. Compared to control group, decreased MBP and NF-L expressions and increased GFAP expression were observed in long term maternal radiation group(all Pï¼0.05). Compared to short term radiation group, the expressions of MBP and NF-L were down-regulated (all Pï¼0.05) and the expression of GFAP was up- regulated(Pï¼0.05) in long term radiation group. CONCLUSION: Prenatal mobile phone radiation might lead to the damage of myelin and axon with activity of astrocytes in cerebellum of male rat offspring, which is related to the extent of radiation.
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Teléfono Celular , Cerebelo/efectos de la radiación , Radiación Electromagnética , Efectos Tardíos de la Exposición Prenatal , Sustancia Blanca/efectos de la radiación , Animales , Cerebelo/patología , Femenino , Proteína Ácida Fibrilar de la Glía/metabolismo , Masculino , Proteína Básica de Mielina/metabolismo , Proteínas de Neurofilamentos/metabolismo , Embarazo , Distribución Aleatoria , Ratas , Sustancia Blanca/patologíaRESUMEN
Proton beam therapy is widely used for treating brain tumor. Despite the efficacy of treatment, the use of this therapy has met some limitations associated with possible damage to normal brain tissues located beyond the tumor site. In this context, the exploration of the harmful effects of protons on the normal brain tissues is of particular interest. We have investigated changes in the total mitochondrial DNA (mtDNA) copy number and identified mtDNA mutant copies in three brain regions (the hippocampus, cortex and cerebellum) of rats after irradiation their whole-head with 150 MeV protons at doses of 3 and 5 Gy. The study was performed in 2-months old male Spraque Dawley rats (n = 5 each group). The mtDNA copy numbers were determined by real-time PCR. The level of mtDNA heteroplasmy was estimated using Surveyor nuclease technology. Our results show that after head exposure to protons, levels of mtDNA copy number in three rat brain regions increase significantly as the levels of mtDNA mutant copies increase. The most significant elevation is observed in the hippocampus. In conclusion, an increase in mtDNA mutant copies may contribute to mitochondrial dysfunction accompanied by increased oxidative stress in different brain regions and promote the development of neurodegenerative diseases and the induction of carcinogenesis.
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Encéfalo/efectos de la radiación , ADN Mitocondrial/efectos de la radiación , Terapia de Protones/efectos adversos , Animales , Encéfalo/metabolismo , Cerebelo/efectos de la radiación , Corteza Cerebral/efectos de la radiación , Variaciones en el Número de Copia de ADN/genética , Hipocampo/efectos de la radiación , Masculino , Mitocondrias/genética , Mutación/genética , Mutación/efectos de la radiación , Protones/efectos adversos , RatasRESUMEN
The Hedgehog signaling pathway shapes our body by regulating the proliferation and differentiation of cells. The spatial and temporal distribution pattern of its ligands finely controls the activity of the Hedgehog pathway during development. To model the control of Hedgehog signaling activities in vitro, we developed a light-inducible Hedgehog signaling activator 6-nitroveratryloxy-carbonyl Smoothened agonist (NVOC-SAG). NVOC-SAG controls the proliferation of mouse cerebellar granule neuron precursor cells and ventral and neural differentiation of human iPS cells in a light dependent manner. The compound provides a new method to control Hedgehog signaling activities.
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Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Cerebelo/efectos de los fármacos , Proteínas Hedgehog/efectos de los fármacos , Luz , Células-Madre Neurales/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Animales , Diferenciación Celular/efectos de la radiación , Proliferación Celular/efectos de la radiación , Cerebelo/citología , Cerebelo/efectos de la radiación , Humanos , RatonesRESUMEN
The prefrontal cortex is central to higher order cognitive function. However, the cerebellum, generally thought to be involved in motor control and learning, has also been implicated in higher order cognition. Recent work using transcranial direct current stimulation (tDCS) provides some support for right cerebellar involvement in higher order cognition, though the results are mixed, and often contradictory. Here, we used cathodal high definition tDCS (HD-tDCS) over the right cerebellum to assess the impact of HD-tDCS on modulating cognitive performance. We predicted that stimulation would result in performance decreases, which would suggest that optimal cerebellar function is necessary for cognitive performance, much like the prefrontal cortex. That is, it is not simply a structure that lends support to complete difficult tasks. While the expected cognitive behavioral effects were present, we did not find effects of stimulation. This has broad implications for cerebellar tDCS research, particularly for those who are interested in using HD-tDCS as a way of examining cerebellar function. Further implications, limitations, and future directions are discussed with particular emphasis on why null findings might be critical in developing a clear picture of the effects of tDCS on the cerebellum.
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Cerebelo/fisiología , Cognición/fisiología , Memoria a Corto Plazo/fisiología , Adulto , Cerebelo/efectos de la radiación , Cognición/efectos de la radiación , Femenino , Humanos , Aprendizaje/fisiología , Aprendizaje/efectos de la radiación , Masculino , Memoria a Corto Plazo/efectos de la radiación , Corteza Prefrontal/fisiología , Corteza Prefrontal/efectos de la radiación , Estimulación Transcraneal de Corriente Directa/efectos adversosRESUMEN
Na,K-ATPase represents the key enzyme maintaining the ionic gradient across plasma membrane. It was documented that in directly irradiated organs the activity of this enzyme is decreased. The aim of present study was to clarify the remote effect of irradiation in mediastinal area on the activity of the Na,K-ATPase in selected brain regions in rats. Ionizing radiation in single dose 25 Gy induced alterations in oxidative status of blood plasma. Irradiation also decreased the activity of the Na,K-ATPase in cerebral cortex. Measurements of kinetic properties of the enzyme dependently on the concentration of energy substrate ATP or cofactor Na+ indicated that the lowered enzyme activity is probably a consequence of decreased number of active molecules of the enzyme, as suggested by lowered Vmax values (by 13 - 14%). Immunoblot analysis revealed that this effect is connected namely to decreased presence of α2 and α3 subunits (by 25% and 30% respectively). Considering the current concepts about involvement of the malfunction of α2 α3 subunits in development of primary brain dysfunctions, it may be hypothesized that the lowered functionality of those subunits of Na,K-ATPase may represent a predisposition to neurodegenerative disorders after irradiation. The observed effect seems to be localization dependent as the enzyme in cerebellum resisted to irradiation.
Asunto(s)
Corteza Cerebral/efectos de la radiación , Subunidades de Proteína/metabolismo , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Animales , Cerebelo/metabolismo , Cerebelo/efectos de la radiación , Corteza Cerebral/metabolismo , Masculino , Estrés Oxidativo/efectos de la radiación , Ratas Wistar , Rayos XRESUMEN
BACKGROUND: Nasopharyngeal carcinoma (NPC) is sensitive to radiotherapy (RT). However, neurocognitive complications such as memory loss and learning and attention deficits emerge in the survivors of NPC who received RT. It remains unclear how radiation affects patient brain function. This pilot study aimed at finding cerebral functional alterations in NPC patients who have received RT. METHODS: From September 2014 to December 2016, 42 individuals, including 22 NPC patients and 20 normal volunteer controls in National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College, were recruited in this study. All patients received resting-state functional magnetic resonance imaging scans and neurocognitive tests 1 day before the initiation of RT (baseline) and 1 day after the completion of RT; the 20 normal controls were also subjected to the same scans and tests. The amplitude of the low-frequency fluctuations (ALFF) in blood oxygen level-dependent signals and functional connectivity (FC) were used to characterize cerebral functional changes. Independent t test, paired t test, and analysis of variances were used to obtain statistical significance across groups. RESULTS: After RT, NPC patients showed significantly decreased ALFF values in the calcarine sulcus, lingual gyrus, cuneus, and superior occipital gyrus and showed significantly reduced FC mainly in the default mode network (Pâ<â0.05, corrected by AlphaSim). Relative to the controls, ALFF was decreased in the lingual gyrus, calcarine sulcus, cingulate cortex, medial prefrontal gyrus (Pâ<â0.05, corrected by AlphaSim), and FC reduction was found in multiple cerebellar-cerebral regions, including the cerebellum, parahippocampus, hippocampus, fusiform gyrus, inferior frontal gyrus, inferior occipital gyrus, precuneus, and cingulate cortex (Pâ<â0.001, corrected by AlphaSim). CONCLUSIONS: Cerebral functional alterations occur immediately after RT. This study may provide an explanation for the cognitive deficits in the morphologically normal-appearing brains of NPC patients after RT and may contribute to the understanding of the complex mechanism of RT.
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Imagen por Resonancia Magnética/métodos , Carcinoma Nasofaríngeo/diagnóstico por imagen , Carcinoma Nasofaríngeo/patología , Adulto , Encéfalo/diagnóstico por imagen , Encéfalo/efectos de la radiación , Mapeo Encefálico , Cerebelo/diagnóstico por imagen , Cerebelo/patología , Cerebelo/efectos de la radiación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo/radioterapia , Proyectos PilotoRESUMEN
Spinocerebellar ataxia type 3 (SCA3) is a polyglutamine neurodegenerative disease resulting from the misfolding and accumulation of a pathogenic protein, causing cerebellar dysfunction, and this disease currently has no effective treatments. Far-infrared radiation (FIR) has been found to protect the viability of SCA3 cells by preventing mutant ataxin-3 protein aggregation and promoting autophagy. However, this possible treatment still lacks in vivo evidence. This study assessed the effect of FIR therapy on SCA3 in vivo by using a mouse model over 28 weeks. Control mice carried a healthy wild-type ATXN3 allele that had a polyglutamine tract with 15 CAG repeats (15Q), whereas SCA3 transgenic mice possessed an allele with a pathological polyglutamine tract with expanded 84 CAG (84Q) repeats. The results showed that the 84Q SCA3 mice displayed impaired motor coordination, balance abilities, and gait performance, along with the associated loss of Purkinje cells in the cerebellum, compared with the normal 15Q controls; nevertheless, FIR treatment was sufficient to prevent those defects. FIR significantly improved performance in terms of maximal contact area, stride length, and base support in the forepaws, hindpaws, or both. Moreover, FIR treatment supported the survival of Purkinje cells in the cerebellum and promoted the autophagy, as reflected by the induction of autophagic markers, LC3II and Beclin-1, concomitant with the reduction of p62 and ataxin-3 accumulation in cerebellar Purkinje cells, which might partially contribute to the rescue mechanism. In summary, our results reveal that FIR confers therapeutic effects in an SCA3 transgenic animal model and therefore has considerable potential for future clinical use.
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Cerebelo/patología , Rayos Infrarrojos/uso terapéutico , Enfermedad de Machado-Joseph/patología , Enfermedad de Machado-Joseph/radioterapia , Actividad Motora , Animales , Ataxina-3/genética , Ataxina-3/metabolismo , Autofagia/efectos de la radiación , Cerebelo/metabolismo , Cerebelo/efectos de la radiación , Modelos Animales de Enfermedad , Marcha/efectos de la radiación , Enfermedad de Machado-Joseph/fisiopatología , Ratones Endogámicos C57BL , Ratones Transgénicos , Actividad Motora/efectos de la radiación , Equilibrio Postural/efectos de la radiación , Distribución AleatoriaRESUMEN
Radio-frequency (RF) field inhomogeneities and higher levels of specific absorption rate (SAR) still present great challenges in ultrahigh-field (UHF) MRI. In this study, an in-depth analysis of the eigenmodes of a 20-channel transmit Tic-Tac-Toe (TTT) RF array for 7T neuro MRI is presented. The eigenmodes were calculated for five different Z levels (along the static magnetic field direction) of the coil. Four eigenmodes were obtained for each Z level (composed of 4 excitation ports), and they were named based on the characteristics of their field distributions: quadrature, opposite-phase, anti-quadrature, and zero-phase. Corresponding finite-difference time-domain (FDTD) simulations were performed and experimental B1+ field maps were acquired using a homogeneous spherical phantom and human head (in-vivo). The quadrature mode is the most efficient and it excites the central brain regions; the opposite-phase mode excites the brain peripheral regions; anti-quadrature mode excites the head periphery; and the zero-phase mode excites cerebellum and temporal lobes. Using this RF array, up to five eigenmodes (from five different Z levels) can be simultaneously excited. The superposition of these modes has the potential to produce homogeneous excitation with full brain coverage and low levels of SAR at 7T MRI.
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Cerebelo/diagnóstico por imagen , Simulación por Computador , Imagen por Resonancia Magnética/métodos , Lóbulo Temporal/diagnóstico por imagen , Cerebelo/efectos de la radiación , Campos Electromagnéticos , Cabeza/diagnóstico por imagen , Cabeza/efectos de la radiación , Humanos , Campos Magnéticos , Cavidad Nasal/diagnóstico por imagen , Cavidad Nasal/efectos de la radiación , Fantasmas de Imagen , Ondas de Radio , Lóbulo Temporal/efectos de la radiaciónRESUMEN
Growing evidence suggests that the cerebellum is not only involved in motor functions, but it significantly contributes to sensory and cognitive processing as well. In particular, it has been hypothesized that the cerebellum identifies recurrent serial events and recognizes their violations. Here we used transcranial magnetic stimulation (TMS) to shed light on the role of the cerebellum in short-term memory of visual sequences. In two experiments, we found that TMS over the right cerebellar hemisphere impaired participants' ability to recognize the correct order of appearance of geometrical stimuli varying in shape and/or size. In turn, cerebellar TMS did not affect recognition of highly familiar short sequences of letters or numbers. Overall, our data suggest that the cerebellum is involved in memorizing the order in which (concatenated) stimuli appear, this process being important for sequence learning.
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Sensibilización del Sistema Nervioso Central/fisiología , Cerebelo/fisiología , Cognición/fisiología , Memoria a Corto Plazo/fisiología , Cerebelo/efectos de la radiación , Cognición/efectos de la radiación , Humanos , Masculino , Memoria a Corto Plazo/efectos de la radiación , Actividad Motora/fisiología , Estimulación Magnética Transcraneal , Adulto JovenRESUMEN
The cerebellum can influence the responsiveness of the primary motor cortex (M1) to undergo spike timing-dependent plastic changes through a complex mechanism involving multiple relays in the cerebello-thalamo-cortical pathway. Previous TMS studies showed that cerebellar cortex excitation can block the increase in M1 excitability induced by a paired-associative stimulation (PAS), while cerebellar cortex inhibition would enhance it. Since cerebellum is known to be affected in many types of dystonia, this bidirectional modulation was assessed in 22 patients with cervical dystonia and 23 healthy controls. Exactly opposite effects were found in patients: cerebellar inhibition suppressed the effects of PAS, while cerebellar excitation enhanced them. Another experiment comparing healthy subjects maintaining the head straight with subjects maintaining the head turned as the patients found that turning the head is enough to invert the cerebellar modulation of M1 plasticity. A third control experiment in healthy subjects showed that proprioceptive perturbation of the sterno-cleido-mastoid muscle had the same effects as turning the head. We discuss these finding in the light of the recent model of a mesencephalic head integrator. We also suggest that abnormal cerebellar processing of the neck proprioceptive information drives dysfunctions of the integrator in cervical dystonia.
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Trastornos Somatosensoriales/patología , Tortícolis/fisiopatología , Adulto , Anciano , Cerebelo/efectos de la radiación , Estimulación Eléctrica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estimulación Magnética Transcraneal , Adulto JovenRESUMEN
BACKGROUND: The present study has investigated the effects of mobile phone (900-1800 MHz)-induced electromagnetic radiation on redox status in the heart, liver, kidney, cerebellum, and hippocampus of dams and the offspring mice. MATERIALS AND METHODS: Pregnant Balb/C were divided into two groups including the control and the experimental group. The experimental group was exposed to mobile phone (900-1800 MHz), during pregnancy (2 h/d for 20 d). The dams and the offspring of both groups were sacrificed and tissues of interest were harvested immediately after delivery. Malondialdehyde (MDA) concentration, total thiol groups (TTG) content, superoxide dismutase (SOD), and catalase (CAT) activities were determined in the tissues. RESULTS: In the experimental groups, MDA levels were significantly increased, while TTG, SOD, and CAT were significantly decreased in the total tissues of dams and their offspring. CONCLUSION: Exposure to mobile phone (900-1800 MHz) during pregnancy induced oxidative stress in tissues of dams and their offspring.
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Teléfono Celular , Radiación Electromagnética , Estrés Oxidativo/efectos de la radiación , Animales , Catalasa/metabolismo , Cerebelo/efectos de la radiación , Modelos Animales de Enfermedad , Femenino , Corazón/efectos de la radiación , Humanos , Riñón/efectos de la radiación , Hígado/efectos de la radiación , Malondialdehído/metabolismo , Ratones , Ratones Endogámicos BALB C , Embarazo , Distribución Aleatoria , Compuestos de Sulfhidrilo/metabolismo , Superóxido Dismutasa/metabolismoRESUMEN
Regeneration of several organs involves adaptive reprogramming of progenitors, but the intrinsic capacity of the developing brain to replenish lost cells remains largely unknown. Here we found that the developing cerebellum has unappreciated progenitor plasticity, since it undergoes near full growth and functional recovery following acute depletion of granule cells, the most plentiful neuron population in the brain. We demonstrate that following postnatal ablation of granule cell progenitors, Nestin-expressing progenitors, specified during mid-embryogenesis to produce astroglia and interneurons, switch their fate and generate granule neurons in mice. Moreover, Hedgehog signaling in two Nestin-expressing progenitor populations is crucial not only for the compensatory replenishment of granule neurons but also for scaling interneuron and astrocyte numbers. Thus, we provide insights into the mechanisms underlying robustness of circuit formation in the cerebellum and speculate that adaptive reprogramming of progenitors in other brain regions plays a greater role than appreciated in developmental regeneration.
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Cerebelo/fisiología , Nestina/fisiología , Células-Madre Neurales/fisiología , Neurogénesis/fisiología , Neuronas/fisiología , Animales , Animales Recién Nacidos , Astrocitos/fisiología , Cerebelo/efectos de la radiación , Femenino , Proteínas Hedgehog/fisiología , Interneuronas/fisiología , Masculino , Ratones , Ratones Transgénicos , Nestina/metabolismo , Células-Madre Neurales/metabolismo , Neuronas/efectos de la radiaciónRESUMEN
Cervical dystonia (CD) is the most common type of focal dystonia, causing abnormal movements of the neck and head. In this study, we used noninvasive imaging to investigate the motor system of patients with CD and uncover the neural correlates of dystonic symptoms. Furthermore, we examined whether a commonly prescribed anticholinergic medication in CD has an effect on the dystonia-related brain abnormalities. Participants included 16 patients with CD and 16 healthy age-matched controls. We collected functional MRI scans during a force task previously shown to extensively engage the motor system, and diffusion and T1-weighted MRI scans from which we calculated free-water and brain tissue densities. The dystonia group was also scanned ca. 2 h after a 2-mg dose of trihexyphenidyl. Severity of dystonia was assessed pre- and post-drug using the Burke-Fahn-Marsden Dystonia Rating Scale. Motor-related activity in CD was altered relative to controls in the primary somatosensory cortex, cerebellum, dorsal premotor and posterior parietal cortices, and occipital cortex. Most importantly, a regression model showed that increased severity of symptoms was associated with decreased functional activity of the somatosensory cortex and increased activity of the cerebellum. Structural imaging measures did not differ between CD and controls. The single dose of trihexyphenidyl altered the fMRI signal in the somatosensory cortex but not in the cerebellum. Symptom severity was not significantly reduced post-treatment. Findings show widespread changes in functional brain activity in CD and most importantly that dystonic symptoms relate to disrupted activity in the somatosensory cortex and cerebellum. Hum Brain Mapp 38:4563-4573, 2017. © 2017 Wiley Periodicals, Inc.
Asunto(s)
Cerebelo/efectos de la radiación , Actividad Motora/fisiología , Corteza Sensoriomotora/fisiopatología , Tortícolis/fisiopatología , Antidiscinéticos/uso terapéutico , Toxinas Botulínicas/uso terapéutico , Mapeo Encefálico , Cerebelo/diagnóstico por imagen , Cerebelo/efectos de los fármacos , Cerebelo/fisiopatología , Estudios de Cohortes , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Actividad Motora/efectos de los fármacos , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/efectos de los fármacos , Vías Nerviosas/fisiopatología , Fármacos Neuromusculares/uso terapéutico , Corteza Sensoriomotora/diagnóstico por imagen , Corteza Sensoriomotora/efectos de los fármacos , Índice de Severidad de la Enfermedad , Tortícolis/diagnóstico por imagen , Tortícolis/tratamiento farmacológico , Trihexifenidilo/uso terapéuticoRESUMEN
The pathological effects of exposure to an electromagnetic field (EMF) during childhood and adolescence may be greater than those from exposure during adulthood. We investigated possible pathological changes in the cerebellum of adolescent rats exposed to 900 MHz EMF daily for 25 days. We used three groups of six 21-day-old male rats as follows: unexposed control group (Non-EG), sham-exposed group (Sham-EG) and an EMF-exposed group (EMF-EG). EMF-EG rats were exposed to EMF in an EMF cage for 1 h daily from postnatal days 21 through 46. Sham-EG rats were placed in the EMF cage for 1 h daily, but were not subjected to EMF. No procedures were performed on the Non-EG rats. The cerebellums of all animals were removed on postnatal day 47, sectioned and stained with cresyl violet for histopathological and stereological analyses. We found significantly fewer Purkinje cells in the EMF-EG group than in the Non-EG and Sham-EG groups. Histopathological evaluation revealed alteration of normal Purkinje cell arrangement and pathological changes including intense staining of neuron cytoplasm in the EMF-EG group. We found that exposure to continuous 900 MHz EMF for 1 h/day during adolescence can disrupt cerebellar morphology and reduce the number of Purkinje cells in adolescent rats.
Asunto(s)
Cerebelo/efectos de la radiación , Campos Electromagnéticos , Animales , Recuento de Células , Cerebelo/anatomía & histología , Cerebelo/química , Masculino , Células de Purkinje/química , Células de Purkinje/efectos de la radiación , Ratas , Factores de TiempoRESUMEN
The current study aimed to investigate the altered cerebellar-cerebral functional connectivity (FC) induced by radiotherapy to nasopharyngeal carcinoma (NPC) patients. Twenty-four NPC patients without treatment, and 35 NPC patients receiving radiotherapy underwent functional MRI scanning. Montreal cognitive assessment (MoCA) was performed to evaluate the cognitive status of all participants. FC between 10 predefined cerebellar seeds, which were demonstrated to be involved in different brain functional networks, and all brain voxels was obtained for each participant. Using a second-level two-sample t-test, three significantly different FCs between the two patient groups were found, including the connections between the left lobule VIII and the right medial frontal gyrus, the left lobule VIII and the right crus I, and the right lobule VIIb and the right fusiform gyrus. The altered cerebellar-cerebral FCs were also significantly correlated to the MoCA score, as well as the attention score, one of the seven subscores in MoCA. We suggested that the altered cerebellar-cerebral FCs may underlie the radiation-induced cognitive deficits in NPC patients, especially in the domain of attention. Furthermore, considering the functional networks in which the altered connections involved, the anticorrelation between the default network and dorsal attention network may be impaired, and the mediating function of the frontoparietal network to dorsal attention network may be disrupted. The significantly altered cerebellar-cerebral FC may serve as the potential biomarker in revealing the radiation-induced functional abnormalities and may help in the early intervention to the cognitive impairment.
Asunto(s)
Carcinoma/radioterapia , Cerebelo/efectos de la radiación , Corteza Cerebral/efectos de la radiación , Neoplasias Nasofaríngeas/radioterapia , Adulto , Mapeo Encefálico , Carcinoma/diagnóstico por imagen , Carcinoma/fisiopatología , Carcinoma/psicología , Cerebelo/diagnóstico por imagen , Cerebelo/fisiopatología , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/fisiopatología , Trastornos del Conocimiento/diagnóstico por imagen , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/fisiopatología , Humanos , Imagen por Resonancia Magnética , Pruebas de Estado Mental y Demencia , Persona de Mediana Edad , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/diagnóstico por imagen , Neoplasias Nasofaríngeas/fisiopatología , Neoplasias Nasofaríngeas/psicología , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/fisiopatología , Vías Nerviosas/efectos de la radiación , Adulto JovenRESUMEN
Interferon-stimulated gene 15 (ISG15), an antagonist of the ubiquitin pathway, is elevated in cells and brain tissues obtained from ataxia telangiectasia (A-T) patients. Previous studies reveal that an elevated ISG15 pathway inhibits ubiquitin-dependent protein degradation, leading to activation of basal autophagy as a compensatory mechanism for protein turnover in A-T cells. Also, genotoxic stress (ultraviolet [UV] radiation) deregulates autophagy and induces aberrant degradation of ubiquitylated proteins in A-T cells. In the current study, we show that, as in A-T cells, ISG15 protein expression is elevated in cerebellums and various other tissues obtained from Atm-compromised mice in an Atm-allele-dependent manner (Atm+/+ < Atm+/- < Atm-/-). Notably, in cerebellums, the brain part primarily affected in A-T, levels of ISG15 were significantly greater (3-fold higher) than cerebrums obtained from the same set of mice. Moreover, as in A-T cell culture, UV induces aberrant degradation of ubiquitylated proteins and autophagy in Atm-deficient, but not in Atm-proficient, cerebellar brain slices grown in culture. Thus, the ex vivo organotypic A-T mouse brain culture model mimics that of an A-T human cell culture model and could be useful for studying the role of ISG15-dependent proteinopathy in cerebellar neurodegeneration, a hallmark of A-T in humans.