RESUMO
Paradoxical sleep deprivation (PSD) is prevalent in modern society, and impaired memory is one of its serious consequences. The pathogenic mechanism is still unclear, and the therapeutic strategies for PSD are limited. Here, we found that quercetin treatment ameliorated memory impairments caused by PSD in a dose-dependent manner in an animal model. Quercetin could restore the dynamic changes of the gamma band while the animals performed novel object recognition (NOR) tasks as determined by electroencephalogram analysis. Morphological analysis showed that quercetin, by targeting the hippocampal CA1 region, strikingly ameliorated the overactivation of microglia induced by PSD. Mechanistically, quercetin inhibited the toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and nuclear factor kappa-b (NF-κB) cascade, which is critical for abnormal microglial activation following PSD stress. Our results provided experimental evidence for the therapeutic effects of quercetin on PSD-related memory impairments by suppressing TLR4/MyD88/NF-κB signaling that mediated abnormal microglia activation in the hippocampus.
Assuntos
Transtornos da Memória , Microglia , Quercetina , Animais , Camundongos , Modelos Animais de Doenças , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/etiologia , Microglia/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , Quercetina/farmacologia , Quercetina/uso terapêutico , Sono REM/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismoRESUMO
Evidence reveals that gut dysbiosis is involved in bidirectional interactions in gut-brain axis and participates in the progress of multiple disorders like anxiety. Gut microbes in early life are crucial for establishment of host health. We aimed to investigate whether early life probiotics Lactobacillus rhamnosus GG (LGG) colonization could relieve anxiety in adulthood through regulation of gut-brain axis. Live or fixed LGG was gavaged to C57BL/6 female mice from day 18 of pregnancy until natural birth, and newborn mice from day 1 to day 5 respectively. In this study, we found that live LGG could be effectively colonized in the intestine of offspring. LGG colonization increased intestinal villus length and colonic crypt depth, accompanied with barrier function protection before weaning. Microbiota composition by 16S rRNA sequencing showed that some beneficial bacteria, such as Akkermansia and Bifidobacteria, were abundant in LGG colonization group. The protective effect of LGG on gut microbiota persisted from weaning to adulthood. Intriguingly, behavioral results assessed by elevated plus mazed test and open field test demonstrated relief of anxiety-like behavior in adult LGG-colonized offspring. Mechanically, LGG colonization activated epithelial growth factor receptor (EGFR) and enhanced serotonin transporter (SERT) expression and modulated serotonergic system in the intestine, and increased brain-derived neurotrophic factor and γ-aminobutyric acid receptor levels in the hippocampus and amygdala. Blocking EGFR blunted LGG-induced the increased SERT and zonula occludens-1 expression. Collectively, early life LGG colonization could protect intestinal barrier of offspring and modulate gut-brain axis in association with relief of anxiety-like behavior in adulthood.
Assuntos
Lacticaseibacillus rhamnosus , Probióticos , Animais , Ansiedade , Eixo Encéfalo-Intestino , Receptores ErbB/metabolismo , Feminino , Lacticaseibacillus rhamnosus/genética , Lacticaseibacillus rhamnosus/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Gravidez , Probióticos/uso terapêutico , RNA Ribossômico 16S/metabolismo , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismoRESUMO
Anxiety disorder is a common emotional handicap, which seriously affects the normal life of patients and endangers their physical and mental health. The prefrontal cortex is a key brain region which is responsible for anxiety. Action potential and behavioral data of rats in the elevated plus maze (EPM) during anxiety (an innate anxiety paradigm) can be obtained simultaneously by using the in vivo and in conscious animal multi-channel microelectrode array recording technique. Based on maximum likelihood estimation (MLE), the action potential causal network was established, network connectivity strength and global efficiency were calculated, and action potential causal network connectivity pattern of the medial prefrontal cortex was quantitatively characterized. We found that the entries (44.13±6.99) and residence period (439.76±50.43) s of rats in the closed arm of the elevated plus maze were obviously higher than those in the open arm [16.50±3.25, P<0.001; (160.23±48.22) s, P<0.001], respectively. The action potential causal network connectivity strength (0.017 3±0.003 6) and the global efficiency (0.044 2±0.012 8) in the closed arm were both higher than those in the open arm (0.010 4±0.003 2, P<0.01; 0.034 8±0.011 4, P<0.001), respectively. The results suggest that the changes of action potential causal network in the medial prefrontal cortex are related to anxiety state. These data could provide support for the study of the brain network mechanism in prefrontal cortex during anxiety.
Assuntos
Ansiedade , Córtex Pré-Frontal , Potenciais de Ação , Animais , Ansiedade/fisiopatologia , Transtornos de Ansiedade , Humanos , Córtex Pré-Frontal/fisiopatologia , RatosRESUMO
The addition of surfactant in tablet was a well-defined approach to improve drug dissolution rate. While the selected surfactant played a vital role in improving the wettability of tablet by medium, it was equally important to improve the dissolution rate by permeation effect due to production of pores or the reduced inter-particle adhesion. Furthermore, understanding the mechanism of dissolution rate increased was significant. In this work, contact angle measurement was taken up as an alternative approach for understanding the dissolution rate enhancement for tablet containing surfactant. Ethylcellulose, as a substrate, was used to prepare tablet. Four surfactants, sodium dodecyl sulfate (SDS), sodium dodecylbenzenesulfonate (SDBS), dodecyltrimethylammonium bromide (DTAB), and sodium lauryl sulfonate (SLS), were used. Berberine hydrochloride, metformin hydrochloride, and rutin were selected as model drugs. The contact angle of tablet in the absence and presence of surfactant was measured to explore the mechanism. The dissolution test was investigated to verify the mechanism and to establish a correlation with the contact angle. The result showed that the mechanism was the penetration effect rather than the wetting effect. The dissolution increased with a reduction in the contact angle. DTAB was found to obtain the highest level of dissolution enhancement and the lowest contact angle, while SDS, SDBS, and SLS were found to be the less effective in both dissolution enhancement and contact angle decrease. Therefore, contact angle was a good indicator for dissolution behavior besides exploring the mechanism of increased dissolution, which shows great potential in formula screening.
Assuntos
Celulose/análogos & derivados , Liberação Controlada de Fármacos , Tensoativos/química , Tensoativos/farmacocinética , Celulose/química , Celulose/farmacocinética , Metformina/química , Metformina/farmacocinética , Dodecilsulfato de Sódio/química , Dodecilsulfato de Sódio/farmacocinética , Solubilidade , Comprimidos , MolhabilidadeRESUMO
Ion-exchange fiber undergoes a stoichiometric exchange reaction and has large exchange capability, which makes it a promising candidate as a multiple drug carrier. Because combinatorial effects can act synergistically, additively or antagonistically depending on the ratio of the agents being combined, the objective of this study was to learn the dual drug loading of ion-exchange fiber and develop a mathematical method for precisely control of the loading amount. Atenolol and Gatifloxacin, with different loading behaviors into strong cationic ion-exchange fiber ZB-1, were used to build a representative of dual loading. Not suitable pH value of drug solutions could make simultaneous loading fail, while the change of drug solution volume hardly affected the equilibrium. Ion-exchange groups occupied by the drug which owned lower affinity to fiber could be grabbed by the higher affinity drug, indicating the existence of competition between drugs. Thermodynamic model was introduced to guide the loading prediction and a favorable relevance had been shown between determined and predicted data. The release behaviors of each drug from dual drug-fiber complex were similar to those from single drug-fiber complexes.
Assuntos
Antibacterianos/administração & dosagem , Anti-Hipertensivos/administração & dosagem , Atenolol/administração & dosagem , Cátions/química , Portadores de Fármacos/química , Fluoroquinolonas/administração & dosagem , Antibacterianos/química , Anti-Hipertensivos/química , Atenolol/química , Combinação de Medicamentos , Liberação Controlada de Fármacos , Fluoroquinolonas/química , Gatifloxacina , Troca Iônica , Modelos Químicos , TermodinâmicaRESUMO
To study the effects of surfactants on wettability of excipients, the contact angles of six types of surfactants on the surface of two common excipients and mixture of three surfactants with excipients were measured using hypsometry method. The results demonstrated that contact angle of water on the surface of excipients was associated with hydrophilcity of excipients. Contact angle was lowered with increase in hydrophilic groups of excipient molecules. The sequence of contact angle from small to large was starch < sodium benzoate < polyvinylpyrrolidone < sodium carboxymethylcellulose < sodium alginate < chitosan < hydroxypropyl methyl cellulose Assuntos
Excipientes/química
, Tensoativos/química
, Molhabilidade
, Química Farmacêutica
, Interações Hidrofóbicas e Hidrofílicas
, Comprimidos
, Água
RESUMO
Working memory refers to a system that provides temporary storage and manipulation of the information necessary for complex cognitive tasks. The prefrontal cortex (PFC) and hippocampus (HPC) are major structures contributing to working memory. Accumulating evidence suggests that the HPC-PFC interactions are critical for the successful execution of working memory tasks. Nevertheless, the directional information transmission within the HPC-PFC pathway remains unclear. Using simultaneous multi-electrode recordings, we recorded local field potentials (LFPs) from the medial prefrontal cortex (mPFC) and ventral hippocampus (vHPC) while the rats performed a spatial working memory task in a Y-maze. The directionality of functional interactions between mPFC and vHPC was assessed using the phase-slope index (PSI). Our findings revealed a frequency-specific oscillatory synchrony in the two regions during the spatial working memory task. Furthermore, an increased high-gamma flow from vHPC to mPFC manifested exclusively during correctly performed trials, not observed during incorrect ones. This suggests that the enhanced high-gamma flow reflects behavioral performance in working memory. Consequently, our results indicate an major role of directional frequency-specific communication in the hippocampal-frontal circuit during spatial working memory, providing a potential mechanism for working memory.
Assuntos
Hipocampo , Memória de Curto Prazo , Ratos , Animais , Memória Espacial , Córtex Pré-Frontal , Vias NeuraisRESUMO
Background: Working memory deficits in Alzheimer's disease (AD) are linked to impairments in the retrieval of stored memory information. However, research on the mechanism of impaired working memory retrieval in Alzheimer's disease is still lacking. Objective: The medial prefrontal cortex (mPFC) and mediodorsal thalamus (MD) are involved in memory retrieval. The purpose of this study is to investigate the functional interactions and information transmission between mPFC and MD in the AD model. Methods: We recorded local field potentials from mPFC and MD while the mice (APP/PS1 transgenic model and control) performed a T-maze spatial working memory task. The temporal dynamics of oscillatory activity and bidirectional information flow between mPFC and MD were assessed during the task phases. Results: We mainly found a significant decrease in theta flow from mPFC to MD in APP/PS1 mice during retrieval. Conclusions: Our results indicate an important role of the mPFC-MD input for retrieval and the disrupted information transfer from mPFC to MD may be the underlying mechanism of working memory deficits in APP/PS1 mice.
Assuntos
Doença de Alzheimer , Memória de Curto Prazo , Camundongos , Animais , Doença de Alzheimer/genética , Córtex Pré-Frontal , Tálamo , Transtornos da Memória/etiologia , Camundongos TransgênicosRESUMO
Consuming probiotic products is a solution that people are willing to choose to augment health. As a global health hazard, sleep deprivation (SD) can cause both physical and mental diseases. The present study investigated the protective effects of Lacticaseibacillus rhamnosus GG (LGG), a widely used probiotic, on a SD mouse model. Here, it has been shown that SD induced intestinal damage in mice, while LGG supplementation attenuated disruption of the intestinal barrier and enhanced the antioxidant capacity. Microbiome analysis revealed that SD caused dysbiosis in the gut microbiota, characterized by increased levels of Clostridium XlVa, Alistipes, and Desulfovibrio, as well as decreased levels of Ruminococcus, which were partially ameliorated by LGG. Moreover, SD resulted in elevated pro-inflammatory cytokine concentrations in both the intestine and the brain, while LGG provided protection in both organs. LGG supplementation significantly improved locomotor activity in SD mice. Although heat-killed LGG showed some protective effects in SD mice, its overall efficacy was inferior to that of live LGG. In terms of mechanism, it was found that AG1478, an inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase, could diminish the protective effects of LGG. In conclusion, LGG demonstrated the ability to alleviate SD-induced intestinal barrier dysfunction through EGFR activation and alleviate neuroinflammation.
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Thalamocortical (TC) circuits are essential for sensory information processing. Clinical and preclinical studies of autism spectrum disorders (ASDs) have highlighted abnormal thalamic development and TC circuit dysfunction. However, mechanistic understanding of how TC dysfunction contributes to behavioral abnormalities in ASDs is limited. Here, our study on a Shank3 mouse model of ASD reveals TC neuron hyperexcitability with excessive burst firing and a temporal mismatch relationship with slow cortical rhythms during sleep. These TC electrophysiological alterations and the consequent sensory hypersensitivity and sleep fragmentation in Shank3 mutant mice are causally linked to HCN2 channelopathy. Restoring HCN2 function early in postnatal development via a viral approach or lamotrigine (LTG) ameliorates sensory and sleep problems. A retrospective case series also supports beneficial effects of LTG treatment on sensory behavior in ASD patients. Our study identifies a clinically relevant circuit mechanism and proposes a targeted molecular intervention for ASD-related behavioral impairments.
Assuntos
Transtorno do Espectro Autista , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização , Proteínas do Tecido Nervoso , Tálamo , Animais , Tálamo/metabolismo , Tálamo/patologia , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/metabolismo , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/genética , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Camundongos , Transtorno do Espectro Autista/genética , Transtorno do Espectro Autista/metabolismo , Transtorno do Espectro Autista/fisiopatologia , Transtorno do Espectro Autista/patologia , Lamotrigina/farmacologia , Córtex Cerebral/metabolismo , Córtex Cerebral/patologia , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/metabolismo , Canalopatias/genética , Canalopatias/metabolismo , Canalopatias/patologia , Humanos , Modelos Animais de Doenças , Masculino , Neurônios/metabolismo , Feminino , Camundongos Endogâmicos C57BL , Mutação/genética , Sono/fisiologia , Sono/efeitos dos fármacos , Sono/genética , Canais de PotássioRESUMO
Brain growth spurt (BGS) is the critical period of neuronal growth and synaptic connection. The voltage-gated K(+) channel is the key channel for maintenance of cell excitability and information transfer among neurons. The purpose of the present study is to investigate the critical period of voltage-gated K(+) channel development in hippocampal CA1 neurons during the BGS. Changes of voltage-gated K(+) currents in neurons from acutely isolated hippocampal CA1 brain slices of rats at different ages (0-4 weeks after birth) were recorded by the whole-cell patch-clamp technique. The depolarization voltage was set at +90 mV, and 0 week was set as the control group. The experimental results showed that, with increasing ages (1-4 weeks), the maximum current densities of IA increased by (16.14 ± 0.51)%, (81.73 ± 10.71)%, (106.72 ± 5.29)%, (134.58 ± 8.81)% (n = 10, P < 0.05), and the maximum current densities of IK increased by (16.75 ± 3.88)%, (134.01 ± 2.85)%, (180.56 ± 8.49)%, (194.5 ± 8.53)% (n = 10, P < 0.05), respectively, compared with those in 0 week. During 0-4 weeks after birth, the activation kinetics of IA shifted to left, and the half activation voltages of IA were 14.67 ± 0.75, 13.46 ± 0.64, 8.39 ± 0.87, 4.60 ± 0.96, 0.54 ± 0.92 (mV, n = 10, P < 0.05), respectively; The activation kinetics of IK shifted to left and the half activation voltages of IK were 8.94 ± 0.85, 6.65 ± 0.89, 0.47 ± 1.15, -1.80 ± 0.89, -8.56 ± 1.08 (mV, n = 10, P < 0.05) respectively. The inactivation kinetics of IA also shifted to left, and the half inactivation voltages were -45.68 ± 1.26, -46.81 ± 0.78, -48.64 ± 0.81, -51.96 ± 1.02, -58.31 ± 1.35 (mV, n = 10) respectively at 0, 1, 2, 3 and 4 weeks after birth, which showed no significant changes between 0 and 1 week, but significant decreases during 1-4 weeks after birth (P < 0.05). These results indicate that the current densities of IA and IK increase and the kinetic characteristics of the voltage-gated K(+) channels change with increasing ages during 0-4 weeks after birth, and the differences are especially significant between the 1st week and the 2nd week after birth. These changes may be related to the maturation of hippocampal neurons and the progress of their functions.
Assuntos
Região CA1 Hipocampal/citologia , Potenciais da Membrana , Neurônios/fisiologia , Canais de Potássio de Abertura Dependente da Tensão da Membrana/fisiologia , Animais , Técnicas de Patch-Clamp , RatosRESUMO
The purpose of this research is to investigate the critical period of voltage-gated Na(+) channel development in hippocampal CA1 neurons. Changes of Na(+) currents in acutely isolated hippocampal CA1 neurons of rats at different ages (0-4 weeks after birth) were recorded using the whole-cell patch-clamp technique. The results indicated that the maximum current density of Na(+) channels was increasing with age, and the amplitudes in 1, 2, 3 and 4 weeks respectively grew by (42.76 ± 4.91)%, (146.80 ± 7.63)%, (208.79 ± 5.28)% and (253.72 ± 5.74)% (n = 10, P < 0.05) compared with that in 0 week. The current density in CA1 neurons of 1-2 weeks after birth increased more significantly than those of other groups. The activation curve of Na(+) channel shifted to the left. The half-activation voltages (mV) in 0-2 weeks were -39.06 ± 0.65, -43.41 ± 0.52, -48.29 ± 0.45 (n = 10, P < 0.05), respectively, showing significant age-dependent decrease, and there were no significant changes in other groups. The slope factors of activation curve for each group did not change significantly. There were no regular changes in inactivation curve and no significant changes in half-inactivation voltage. The slope factors of inactivation curve in 1-2 weeks were: 5.77 ± 0.56, 4.42 ± 0.43 (n = 10, P < 0.05). The inactivation rate of the second week after birth was faster than that of the first week, and there were no significant changes during 0-1 week and 2-4 weeks. The recovery from inactivation curve of Na(+) channel shifted to the left. The recovery time declined in 1-3 weeks. Changes of action potential properties were consistent with Na(+) current. These results suggest that the period of 1-2 weeks after birth may be the critical development period of voltage-gated Na(+) channel in hippocampal CA1 neurons. During this time, the distribution of Na(+) channel increases significantly; the activation curve of Na(+) channel shifts to the left; inactivation rate increases as well as recovery time shortens.
Assuntos
Potenciais de Ação , Região CA1 Hipocampal/citologia , Neurônios/fisiologia , Canais de Sódio/fisiologia , Animais , Técnicas de Patch-Clamp , RatosRESUMO
Introduction: Depression is a mental disorder characterized by aberrant exploratory behavior. Environmental factors, such as chronic stress, are commonly used to induce depression-like behavior in rodent models. The medial prefrontal cortex (mPFC) and the basolateral amygdala (BLA) are crucial sites in subjects with chronic stress-induced depression. The transmission of amplitude information from the mPFC to the BLA was abated during exploratory behavior in depressive rats; however, the nature of the phase interaction between these two sites remains unknown. Methods: We used chronic unpredictable mild stress (CUMS) to model depression in rats and acquired local field potentials (LFPs) via multiple electrodes implanted in the mPFC and the BLA while rats (both the control and CUMS groups, respectively) were allowed to explore freely in an open field. The weighted phase lag index (WPLI) within the mPFC and the BLA and phase transfer entropy (PTE) from the mPFC to BLA were computed for two groups of rats (control and CUMS rats) to quantify the phase information transmission. Results: Rats subjected to CUMS showed a decrease in exploratory behavior. The WPLI within the mPFC and the BLA showed strikingly higher phase synchrony at theta frequencies (4-12 Hz) than other frequency bands during exploratory behavior in both the control and CUMS groups. The results of theta PTE from the mPFC to BLA showed that PTE was significantly decreased in the CUMS group compared with the control group. Discussions: These findings demonstrated that attenuated phase information transfer might restrain exploratory behavior in CUMS rats.
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Chronic stress contributes to the onset and exacerbation of major depressive disorder (MDD) through the oscillatory activity in the prefrontal cortex (PFC). However, the oscillations on which chronic social stress converges to yield the behavioral state of social avoidance are largely unknown. Here, we use a chronic social defeat stress model and in vivo electrophysiological recordings to uncover a novel neurophysiological measure that predicts the social behavioral state in stressed animals. First, in this study, we find that chronic social defeat stress model induces depression-like behaviors (anhedonia and social avoidance). Second, we find statistically significant differences in PFC oscillatory activity across different frequency ranges in social behavioral state, and the oscillatory activity correlates with stress-induced behavioral state. Finally, we show that the social behavioral states are accurately decoded from the oscillatory activity based on machine learning. Together, these results demonstrate that naturally occurring differences in PFC oscillation underlie the social behavioral state that accompanies the emergence of stress-induced behavioral dysfunction.
RESUMO
Introduction: Spatial working memory is a kind of short-term memory that allows temporarily storing and manipulating spatial information. Evidence suggests that spatial working memory is processed through three distinctive phases: Encoding, maintenance, and retrieval. Though the medial prefrontal cortex (mPFC) and mediodorsal thalamus (MD) are involved in memory retrieval, how the functional interactions and information transfer between mPFC and MD remains largely unclear. Methods: We recorded local field potentials (LFPs) from mPFC and MD while mice performed a spatial working memory task in T-maze. The temporal dynamics of functional interactions and bidirectional information flow between mPFC and MD was quantitatively assessed by using directed transfer function. Results: Our results showed a significantly elevated information flow from mPFC to MD, varied in time and frequency (theta in particular), accompanying successful memory retrieval. Discussion: Elevated theta information flow, a feature that was absent on error trials, indicates an important role of the directional information transfer from mPFC to MD for memory retrieval.
RESUMO
Exploratory behavior plays a fundamental role in motivation, learning, and well-being of organisms. The open field test (OFT) is a classic method to investigate the exploratory behavior in rodents, also a widely adopted and pharmacologically validated procedure for evaluating anxiety and depression. Several lines of evidence have shown that medial prefrontal cortex (mPFC) and basolateral amygdala (BLA) play crucial roles in anxiety-like or depression-like exploratory behavior. However, the dynamic characterization of the mPFC-BLA network in exploratory behavior is less well understood. Therefore, this study aimed to investigate the information transmission mechanism in the mPFC-BLA network during exploratory behavior. Local field potentials (LFPs) from mPFC and BLA were simultaneously recorded while the rats performed the OFT. Directed transfer function (DTF), which was derived from Granger causal connectivity analysis, was applied to measure the functional connectivity among LFPs. Information flow (IF) was calculated to explore the dynamics of information transmission in the mPFC-BLA network. Our results revealed that, for both mPFC and BLA, the theta-band functional connectivity in periphery was significantly higher than that in center of the open field. The IF from BLA to mPFC in the open field task was significantly higher than that from mPFC to BLA. These results suggest that the functional connectivity and IF in the mPFC-BLA network are related to the exploratory behavior, and information transmission from BLA to mPFC could be predominant for exploratory behavior.
Assuntos
Complexo Nuclear Basolateral da Amígdala/fisiologia , Fenômenos Eletrofisiológicos/fisiologia , Comportamento Exploratório/fisiologia , Rede Nervosa/fisiologia , Córtex Pré-Frontal/fisiologia , Animais , Comportamento Animal/fisiologia , Conectoma , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: Transcranial direct current stimulation (tDCS) and functional electrical stimulation (FES) are two widely applied methods of electrical stimulation for motor recovery among stroke patients. This systematic review and meta-analysis investigated the efficacy of tDCS and FES for strength production in stroke patients. TYPE: Systematic review. LITERATURE SURVEY: Studies that explored the effects of tDCS or FES on the strength production of paralyzed muscles in stroke patients were retrieved on a comprehensive set of three databases: (1) Google Scholar, (2) PubMed, and (3) the Cochrane Database of Systematic Reviews until July 2019. METHODOLOGY: Systematic study retrieval led to the inclusion of 15 studies that reported on strength production effects after tDCS and FES interventions among stoke patients. A sham control group and randomization were used in each study. The 15 studies included 20 comparisons with sham controls, 7 of which involved tDCS and 13 of which involved FES. SYNTHESIS: Random-effects models showed that strength production was improved after tDCS (effect size [ES] = 0.52, 95% confidence interval [CI] = 0.35-0.69, P < .001, Z = 6.05) and FES (ES = 0.47, 95% CI = 0.16-0.78, P < .003, Z = 2.99). Additionally, tDCS was shown to improve strength production in the acute (ES = 0.52, 95% CI = 0.24-0.80, P < .001, Z = 3.65), subacute (ES = 0.85, 95% CI = 0.37-1.32, P < .001, Z = 3.51), but not chronic (ES = 0.06, 95% CI = -0.47-0.60, P = .82, Z = 0.23) phases of stroke recovery. Out of the 13 studies involving FES, 12 investigated strength production in the chronic phase and one investigated in the acute phase, showing a positive effect in these two stages. CONCLUSIONS: The results of the meta-analysis showed that tDCS and FES successfully improved strength production in stroke patients.
Assuntos
Córtex Motor , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Estimulação Transcraniana por Corrente Contínua , Estimulação Elétrica , Humanos , Músculos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapiaRESUMO
Depression is a common neuropsychiatric illness observed worldwide, and reduced interest in exploration is one of its symptoms. The control of dysregulated medial prefrontal cortex (mPFC) over the basolateral amygdala (BLA) is related to depression. However, the oscillation interaction in the mPFC-BLA circuit has remained elusive. Therefore, this study used phase-amplitude coupling (PAC), which provides complicated forms of information transmission by the phase of low-frequency rhythm, modulating the amplitude of high-frequency rhythm, and has a potential application for the treatment of neurological disease. The chronic unpredictable mild stress (CUMS) was used to prepare the rat models of depression. Moreover, multichannel in vivo recording was applied to obtain the local field potentials (LFPs) of the mPFC, the BLA in rats in control, and CUMS groups, while they explored the open field. The results showed prominent coupling between the phase of theta oscillation (4-12 Hz) in the mPFC and the amplitude of high-gamma oscillation (70-120 Hz) in the BLA. Compared to the control group, this theta-gamma PAC was significantly decreased in the CUMS group, which was accompanied by the diminished exploratory behaviour. The results indicate that the coupling between the phase of theta in the mPFC and the amplitude of gamma in the BLA is involved in exploratory behaviour, and this decreased coupling may inhibit exploratory behaviour of rats exposed to CUMS.
RESUMO
ASH1L, a histone methyltransferase, is identified as a top-ranking risk factor for autism spectrum disorder (ASD), however, little is known about the biological mechanisms underlying the link of ASH1L haploinsufficiency to ASD. Here we show that ASH1L expression and H3K4me3 level are significantly decreased in the prefrontal cortex (PFC) of postmortem tissues from ASD patients. Knockdown of Ash1L in PFC of juvenile mice induces the downregulation of risk genes associated with ASD, intellectual disability (ID) and epilepsy. These downregulated genes are enriched in excitatory and inhibitory synaptic function and have decreased H3K4me3 occupancy at their promoters. Furthermore, Ash1L deficiency in PFC causes the diminished GABAergic inhibition, enhanced glutamatergic transmission, and elevated PFC pyramidal neuronal excitability, which is associated with severe seizures and early mortality. Chemogenetic inhibition of PFC pyramidal neuronal activity, combined with the administration of GABA enhancer diazepam, rescues PFC synaptic imbalance and seizures, but not autistic social deficits or anxiety-like behaviors. These results have revealed the critical role of ASH1L in regulating synaptic gene expression and seizures, which provides insights into treatment strategies for ASH1L-associated brain diseases.
Assuntos
Transtorno Autístico/metabolismo , Proteínas de Ligação a DNA/metabolismo , Epigênese Genética , Histona-Lisina N-Metiltransferase/metabolismo , Córtex Pré-Frontal/metabolismo , Convulsões/metabolismo , Animais , Transtorno do Espectro Autista/genética , Transtorno do Espectro Autista/metabolismo , Transtorno Autístico/genética , Encéfalo/metabolismo , Proteínas de Ligação a DNA/deficiência , Proteínas de Ligação a DNA/genética , Modelos Animais de Doenças , Feminino , Histona-Lisina N-Metiltransferase/genética , Histonas/metabolismo , Homeostase , Humanos , Deficiência Intelectual/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Células Piramidais/metabolismo , Fatores de Risco , Convulsões/fisiopatologiaRESUMO
Exposure to prolonged stress in critical developmental periods induces heightened vulnerability to psychiatric disorders, which may have sex-specific consequences. Here we investigate the neuronal circuits mediating behavioral changes in mice after chronic adolescent social isolation stress. Escalated aggression is exhibited in stressed males, while social withdrawal is shown in stressed females. In vivo multichannel recordings of free-moving animals indicate that pyramidal neurons in prefrontal cortex (PFC) from stressed males exhibit the significantly decreased spike activity during aggressive attacks, while PFC pyramidal neurons from stressed females show a blunted increase of discharge rates during sociability tests. Chemogenetic and electrophysiological evidence shows that PFC hypofunctioning and BLA principal neuron hyperactivity contribute to the elevated aggression in stressed males, while PFC hypofunctioning and VTA dopamine neuron hypoactivity contribute to the diminished sociability in stressed females. These results establish a framework for understanding the circuit and physiological mechanisms underlying sex-specific divergent effects of stress.