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1.
Nan Fang Yi Ke Da Xue Xue Bao ; 40(7): 972-980, 2020 Jul 30.
Artigo em Chinês | MEDLINE | ID: mdl-32895149

RESUMO

OBJECTIVE: To investigate the effects of acid-sensing ion channels (ASICs) on electrophysiological epileptic activities of mouse hippocampal pyramidal neurons in the extracellular acidotic condition. METHODS: We investigated effects of extracellular acidosis on epileptic activities induced by elevated extracellular K + concentration or the application of an antagonist of GABAA receptors in perfusate of mouse hippocampal slices under field potential recordings. We also tested the effects of extracellular acidosis on neuronal excitability under field potential recording and evaluated the changes in epileptic activities of the neurons in response to pharmacological inhibition of ASICs using a specific inhibitor of ASICs. RESULTS: Extracellular acidosis significantly suppressed epileptic activities of the hippocampal neurons by converting ictal-like epileptic activities to non-ictal-like epileptic activities in both high [K +]o and disinhibition models, and also suppressed the intrinsic excitability of the neurons. ASICs inhibitor did not antagonize the inhibitory effect of extracellular acidosis on ictal epileptic activities and intrinsic neuronal excitability, but exacerbated non-ictal epileptic activities of the neurons in extracellular acidotic condition in both high [K+]o and disinhibition models. CONCLUSIONS: ASICs can differentially modulate ictal-like and non-ictallike epileptic activities via its direct actions on excitatory neurons.


Assuntos
Acidose , Canais Iônicos Sensíveis a Ácido , Animais , Hipocampo , Concentração de Íons de Hidrogênio , Camundongos , Células Piramidais
2.
Nan Fang Yi Ke Da Xue Xue Bao ; 40(8): 1097-1102, 2020 Aug 30.
Artigo em Chinês | MEDLINE | ID: mdl-32895179

RESUMO

OBJECTIVE: To explore the protective effect of vitamin E (VE) against radiation injury of hippocampal neurons in mice and explore the possible mechanism. METHODS: Cultured HT-22 and U251 cells with or without exposure to 8 Gy irradiation were treated with VE (200 µmol/L for 24 h), ferroptosis inhibitor (ferrostatin-1, 5 µmol/L for 24 h), apoptosis inhibitor (ZVAD-FMK, 2 µmol/L), or necroptosis inhibitor (100 µmol/L). MTT assay was used to evaluate the cell viability after the treatments, and reduced glutathione (GSH), malondialdehyde (MDA), lipid reactive oxygen species (lipid ROS), and intracellular iron ion levels were detected for assessment of ferroptosis. The mice exposed to 16 Gy irradiation with or without vitamin E (500 U/kg) treatment for 6 weeks were assessed for behavioral changes and cognitive functions using Morris water maze test. RESULTS: Treatment with VE significantly promoted the cell survival following irradiation in HT-22 cells (P < 0.05) but not in U251 cells (P > 0.05). Ferrostatin-1, but not ZVAD or the necroptosis inhibitor, promoted the survival of HT-22 cells following the irradiation. Exposure to irradiation significantly increased ferroptosis-related oxidative stress level in HT-22 cells, manifested by decreased GSH level and increased MDA, lipid ROS and intracellular iron ion levels (P < 0.05); treatment with VE and ferrostatin-1 both obviously reversed radiation-induced ferroptosis-related oxidative stress in the cells (P < 0.05). In Morris water maze test, the mice with radiation exposure showed obviously increased exploration time and distance (P < 0.05), which were significantly decreased after treatment with VE (P < 0.05). CONCLUSIONS: Vitamin E reduces radiation injury by inhibiting ferroptosis in the hippocampal neurons in mice.


Assuntos
Lesões por Radiação , Animais , Ferroptose , Hipocampo , Camundongos , Neurônios , Vitamina E
3.
Artigo em Russo | MEDLINE | ID: mdl-32929929

RESUMO

OBJECTIVE: To compare the effects of cortexin, cerebrolysin and actovegin on memory impairment, cerebral circulation and morphological changes in the hippocampus of rats with chronic brain ischemia. MATERIAL AND METHODS: The study was conducted using male rats with chronic brain ischemia caused by stenosis of the common carotid arteries by 50%. Animals received cortexin (0,3; 1 or 3 mg/kg), cerebrolysin (0,8; 2,5 or 7,5 ml/kg) and actovegin (5 ml/kg) in two 10-day courses with 10 days of treatment break. The severity of cognitive impairment was evaluated using the Morris water maze, passive and active avoidance tests. Cerebral circulation using laser flowmetry and brain hippocampus structures were studied in the end of treatment. RESULTS: Cognitive impairment in animals with chronic brain ischemia was accompanied by the development of pathological changes in the CA1 and CA4 regions of the hippocampus. Administration of cortexin (1 and 3 mg/kg) and cerebrolysin (2.5 and 7.5 ml/kg) to rats with chronic brain ischemia had almost no effect on cerebral blood flow, but contributed to the improvement in memory formation and retrieval processes in the Morris water maze. The treatment effect was comparable for both drugs and persisted after 10 days of treatment break. Morphological assessment showed a decrease in the severity of pathological changes in the hippocampal regions. CONCLUSION: The course-administration of cortexin and cerebrolysin lead to a decrease in the severity of memory impairment and pathomorphological changes in the hippocampus in rats with chronic brain ischemia.


Assuntos
Isquemia Encefálica , Aminoácidos , Animais , Circulação Cerebrovascular , Heme/análogos & derivados , Hipocampo , Peptídeos e Proteínas de Sinalização Intercelular , Masculino , Ratos , Ratos Wistar
4.
Nat Commun ; 11(1): 4590, 2020 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-32929067

RESUMO

An adaptive memory system rarely learns information tabula rasa, but rather builds on prior knowledge to facilitate learning. How prior knowledge influences the neural representation of novel associations remains unknown. Here, participants associated pairs of faces in two conditions: a famous, highly familiar face with a novel face or two novel faces while undergoing fMRI. We examine multivoxel activity patterns corresponding to individual faces before and after learning. The activity patterns representing members of famous-novel pairs becomes separated in the hippocampus, that is, more distinct from one another through learning, in striking contrast to paired novel faces that become similar. In the left inferior frontal gyrus, however, prior knowledge leads to integration, and in a specific direction: the representation of the novel face becomes similar to that of the famous face after learning, suggesting assimilation of new into old memories. We propose that hippocampal separation might resolve interference between existing and newly learned information, allowing cortical assimilation. Thus, associative learning with versus without prior knowledge relies on radically different computations.


Assuntos
Giro do Cíngulo/fisiologia , Hipocampo/fisiologia , Córtex Pré-Frontal/fisiologia , Adulto , Assimetria Facial/fisiopatologia , Feminino , Humanos , Masculino , Memória , Rede Nervosa/fisiologia , Adulto Jovem
5.
Nat Commun ; 11(1): 4388, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32873805

RESUMO

Presynaptic spike timing-dependent long-term depression (t-LTD) at hippocampal CA3-CA1 synapses is evident until the 3rd postnatal week in mice, disappearing during the 4th week. At more mature stages, we found that the protocol that induced t-LTD induced t-LTP. We characterized this form of t-LTP and the mechanisms involved in its induction, as well as that driving this switch from t-LTD to t-LTP. We found that this t-LTP is expressed presynaptically at CA3-CA1 synapses, as witnessed by coefficient of variation, number of failures, paired-pulse ratio and miniature responses analysis. Additionally, this form of presynaptic t-LTP does not require NMDARs but the activation of mGluRs and the entry of Ca2+ into the postsynaptic neuron through L-type voltage-dependent Ca2+ channels and the release of Ca2+ from intracellular stores. Nitric oxide is also required as a messenger from the postsynaptic neuron. Crucially, the release of adenosine and glutamate by astrocytes is required for t-LTP induction and for the switch from t-LTD to t-LTP. Thus, we have discovered a developmental switch of synaptic transmission from t-LTD to t-LTP at hippocampal CA3-CA1 synapses in which astrocytes play a central role and revealed a form of presynaptic LTP and the rules for its induction.


Assuntos
Astrócitos/metabolismo , Hipocampo/crescimento & desenvolvimento , Potenciação de Longa Duração/fisiologia , Transmissão Sináptica/fisiologia , Adenosina/metabolismo , Animais , Feminino , Ácido Glutâmico/metabolismo , Hipocampo/citologia , Masculino , Camundongos , Técnicas de Patch-Clamp , Receptores de Glutamato Metabotrópico/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo
6.
Nat Commun ; 11(1): 4484, 2020 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-32901027

RESUMO

Chronic stress is a key risk factor for mood disorders like depression, but the stress-induced changes in brain circuit function and gene expression underlying depression symptoms are not completely understood, hindering development of novel treatments. Because of its projections to brain regions regulating reward and anxiety, the ventral hippocampus is uniquely poised to translate the experience of stress into altered brain function and pathological mood, though the cellular and molecular mechanisms of this process are not fully understood. Here, we use a novel method of circuit-specific gene editing to show that the transcription factor ΔFosB drives projection-specific activity of ventral hippocampus glutamatergic neurons causing behaviorally diverse responses to stress. We establish molecular, cellular, and circuit-level mechanisms for depression- and anxiety-like behavior in response to stress and use circuit-specific gene expression profiling to uncover novel downstream targets as potential sites of therapeutic intervention in depression.


Assuntos
Aprendizagem da Esquiva/fisiologia , Hipocampo/fisiologia , Proteínas Proto-Oncogênicas c-fos/fisiologia , Animais , Ansiedade/metabolismo , Comportamento Animal/fisiologia , Técnicas de Inativação de Genes , Inativação Gênica , Hipocampo/anatomia & histologia , Hipocampo/citologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neurônios/metabolismo , Proteínas Proto-Oncogênicas c-fos/deficiência , Proteínas Proto-Oncogênicas c-fos/genética , Comportamento Social , Estresse Psicológico
7.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(9): 1017-1026, 2020 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-32933637

RESUMO

OBJECTIVE: To study the effect of advanced maternal age (AMA) on the development of hippocampal neural stem cells in offspring rats. METHODS: Ten 3-month-old and ten 12-month-old female Sprague-Dawley rats were housed individually with 3-month-old male rats (1:1, n=20), whose offspring rats were assigned to a control group and an AMA group. A total of 40 rats were randomly selected from each group. Immunofluorescence assay and Western blot were used to localize and determine the levels of protein expression of Nestin and doublecortin (DCX) on day 7 as well as neuronal nuclear antigen (NeuN) and glial fibrillary acidic protein (GFAP) on day 28 (n=8 for each marker). Immunofluorescence assay was also used to localize the hippocampal expression of polysialylated isoforms of neural cell adhesion molecule (PSA-NCAM) on day 14 (n=8 for each marker). RESULTS: According to the Western blot results, the AMA group had significantly lower protein expression of DCX than the control group (P<0.05), while there were no significant differences in the protein expression of Nestin, NeuN, and GFAP between the two groups (P>0.05). According to the results of immunofluorescence assay, the AMA group had significantly lower protein expression of Nestin, DCX, and PSA-NCAM in the hippocampal dentate gyrus (DG) region than the control group (P<0.05), while there were no significant differences in the above indices in the hippocampal CA1 and CA3 regions between the two groups (P>0.05). The AMA group had significantly higher expression of NeuN in the hippocampal CA1 region than the control group (P<0.01), while there were no significant differences in the expression of NeuN in the hippocampal DG and CA3 regions between the two groups (P>0.05). The AMA group had significantly lower expression of GFAP in the hippocampal CA1, CA3, and DG regions than the control group (P<0.05). CONCLUSIONS: AMA may cause inhibition of proliferation, survival, and migration of hippocampal neural stem cells. AMA may also affect their differentiation into neurons and astrocytes, which will eventually lead to developmental disorders of hippocampal neural stem cells in offspring rats.


Assuntos
Células-Tronco Neurais , Animais , Feminino , Hipocampo , Masculino , Idade Materna , Neurônios , Ratos , Ratos Sprague-Dawley
8.
Medicine (Baltimore) ; 99(33): e21711, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32872049

RESUMO

BACKGROUND: This study will investigate the effects of Spore Powder of Ganoderma Lucidum (SPGL) on CaSR and apoptosis-related proteins (ARP) in hippocampus tissue of epilepsy following dementia. METHODS: This study will retrieve all potential studies from both electronic databases (Cochrane Library, EMBASE, MEDLINE, CINAHL, AMED, and CNKI) and other literature sources to assess the effects of SPGL on CaSR and ARP in hippocampus tissue of epilepsy following dementia. We will search all literature sources from the inception to the present. All eligible case-control studies will be included in this study. Two authors will independently carry out literature selection, data collection, and study quality evaluation. Any divergence will be resolved by another author through discussion. RevMan 5.3 software will be employed for data analysis. RESULTS: This study will summarize existing evidence to assess the effects of SPGL on CaSR and ARP in hippocampus tissue of epilepsy following dementia. CONCLUSIONS: The findings of this study may provide helpful evidence of SPGL on CaSR and ARP in hippocampus tissue of epilepsy following dementia. SYSTEMATIC REVIEW REGISTRATION: INPLASY202070041.


Assuntos
Demência/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Epilepsia/tratamento farmacológico , Hipocampo/efeitos dos fármacos , Reishi , Animais , Demência/complicações , Medicamentos de Ervas Chinesas/farmacologia , Epilepsia/etiologia , Hipocampo/metabolismo , Receptores de Detecção de Cálcio/metabolismo , Revisões Sistemáticas como Assunto
9.
Acta Cir Bras ; 35(7): e202000705, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32785417

RESUMO

Purpose Studies have demonstrated that star fruit consumption by nephropathic patients triggers severe neurotoxic effects that can lead to convulsions or even death. Brain areas likely susceptible to star fruit poisoning have not been investigated. The objective of the present study was to map possible epileptogenic areas susceptible to star fruit intoxication in nephropathic rats. Methods The study analyzed 25 rats (5 groups). Rats in the experimental group underwent bilateral ureteral obstruction surgery and orogastric gavages with star fruit juice. An electroencephalogram was used to confirm convulsive seizures. Urea and creatinine levels were used to confirm the uremia model. Immunohistochemical analysis was used to map cells with c-Fos protein (c-Fos+ cells) to identify brain areas with increased neuronal activity. Control groups included non-nephropathic and nephropathic rats that did not receive star fruit. Results A statistically significant increase (p<0.01) in c-Fos+ cells was noted in nephropathic animals receiving star fruit juice compared to control groups, in brain areas commonly related to epileptogenic neural circuits including the hippocampus, amygdala, rhinal cortex, anterior cingulate area, piriform area, and medial dorsal thalamus. Conclusion These data corroborate the neurotoxic capacity of star fruit in nephropathic patients.


Assuntos
Frutas , Nefropatias , Proteínas Proto-Oncogênicas c-fos , Animais , Encéfalo , Córtex Cerebral , Frutas/envenenamento , Hipocampo , Humanos , Nefropatias/complicações , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos
10.
Nat Commun ; 11(1): 4220, 2020 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-32839437

RESUMO

Post-traumatic stress disorder (PTSD) is characterized by emotional hypermnesia on which preclinical studies focus so far. While this hypermnesia relates to salient traumatic cues, partial amnesia for the traumatic context can also be observed. Here, we show in mice that contextual amnesia is causally involved in PTSD-like memory formation, and that treating the amnesia by re-exposure to all trauma-related cues cures PTSD-like hypermnesia. These findings open a therapeutic perspective based on trauma contextualization and the underlying hippocampal mechanisms.


Assuntos
Amnésia/prevenção & controle , Amnésia/terapia , Condicionamento Psicológico/fisiologia , Memória/fisiologia , Transtornos de Estresse Pós-Traumáticos/prevenção & controle , Transtornos de Estresse Pós-Traumáticos/terapia , Amnésia/fisiopatologia , Animais , Aprendizagem da Esquiva/fisiologia , Sinais (Psicologia) , Emoções , Hipocampo/fisiopatologia , Humanos , Masculino , Camundongos Endogâmicos C57BL , Transtornos de Estresse Pós-Traumáticos/fisiopatologia
11.
Nat Commun ; 11(1): 3980, 2020 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-32769969

RESUMO

Recent research has highlighted a role for the hippocampus and a Posterior Medial cortical network in signaling event boundaries. However, little is known about whether or how these neural processes change over the course of healthy aging. Here, 546 cognitively normal participants 18-88 years old viewed a short movie while brain activity was measured using fMRI. The hippocampus and regions of the Posterior Medial network show increased activity at event boundaries, but these boundary-evoked responses decrease with age. Boundary-evoked activity in the posterior hippocampus predicts performance on a separate test of memory for stories, suggesting that hippocampal activity during event segmentation may be a broad indicator of individual differences in episodic memory ability. In contrast, boundary-evoked responses in the medial prefrontal cortex and middle temporal gyrus increase across the age range. These findings suggest that aging may alter neural processes for segmenting and remembering continuous real-world experiences.


Assuntos
Envelhecimento/fisiologia , Hipocampo/fisiologia , Neurônios/fisiologia , Núcleos Ventrais do Tálamo/fisiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Fatores de Tempo , Adulto Jovem
12.
Nat Commun ; 11(1): 4040, 2020 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-32788583

RESUMO

Children from lower income backgrounds tend to have poorer memory and language abilities than their wealthier peers. It has been proposed that these cognitive gaps reflect the effects of income-related stress on hippocampal structure, but the empirical evidence for this relationship has not been clear. Here, we examine how family income gaps in cognition relate to the anterior hippocampus, given its high sensitivity to stress, versus the posterior hippocampus. We find that anterior (but not posterior) hippocampal volumes positively correlate with family income up to an annual income of ~$75,000. Income-related differences in the anterior (but not posterior) hippocampus also predicted the strength of the gaps in memory and language. These findings add anatomical specificity to current theories by suggesting a stronger relationship between family income and anterior than posterior hippocampal volumes and offer a potential mechanism through which children from different income homes differ cognitively.


Assuntos
Cognição/fisiologia , Hipocampo/anatomia & histologia , Renda , Adolescente , Criança , Pré-Escolar , Família , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Modelos Lineares , Masculino , Memória/fisiologia , Grupos Minoritários , Tamanho do Órgão , Análise e Desempenho de Tarefas , Vocabulário , Adulto Jovem
13.
Science ; 369(6507)2020 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-32855309

RESUMO

Neuronal synapses undergo structural and functional changes throughout life, which are essential for nervous system physiology. However, these changes may also perturb the excitatory-inhibitory neurotransmission balance and trigger neuropsychiatric and neurological disorders. Molecular tools to restore this balance are highly desirable. Here, we designed and characterized CPTX, a synthetic synaptic organizer combining structural elements from cerebellin-1 and neuronal pentraxin-1. CPTX can interact with presynaptic neurexins and postsynaptic AMPA-type ionotropic glutamate receptors and induced the formation of excitatory synapses both in vitro and in vivo. CPTX restored synaptic functions, motor coordination, spatial and contextual memories, and locomotion in mouse models for cerebellar ataxia, Alzheimer's disease, and spinal cord injury, respectively. Thus, CPTX represents a prototype for structure-guided biologics that can efficiently repair or remodel neuronal circuits.


Assuntos
Proteína C-Reativa/farmacologia , Proteínas do Tecido Nervoso/farmacologia , Vias Neurais/efeitos dos fármacos , Precursores de Proteínas/farmacologia , Receptores de AMPA/metabolismo , Proteínas Recombinantes/farmacologia , Sinapses/efeitos dos fármacos , Doença de Alzheimer/terapia , Animais , Proteína C-Reativa/química , Proteína C-Reativa/uso terapêutico , Ataxia Cerebelar/terapia , Modelos Animais de Doenças , Células HEK293 , Hipocampo , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Proteínas do Tecido Nervoso/química , Proteínas do Tecido Nervoso/uso terapêutico , Domínios Proteicos , Precursores de Proteínas/química , Precursores de Proteínas/uso terapêutico , Receptores de Glutamato/genética , Proteínas Recombinantes/química , Proteínas Recombinantes/uso terapêutico , Coluna Vertebral/efeitos dos fármacos , Coluna Vertebral/fisiologia
14.
PLoS Biol ; 18(8): e3000851, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32822389

RESUMO

High levels of the amyloid-beta (Aß) peptide have been shown to disrupt neuronal function and induce hyperexcitability, but it is unclear what effects Aß-associated hyperexcitability may have on tauopathy pathogenesis or propagation in vivo. Using a novel transgenic mouse line to model the impact of human APP (hAPP)/Aß accumulation on tauopathy in the entorhinal cortex-hippocampal (EC-HIPP) network, we demonstrate that hAPP overexpression aggravates EC-Tau aggregation and accelerates pathological tau spread into the hippocampus. In vivo recordings revealed a strong role for hAPP/Aß, but not tau, in the emergence of EC neuronal hyperactivity and impaired theta rhythmicity. Chronic chemogenetic attenuation of EC neuronal hyperactivity led to reduced hAPP/Aß accumulation and reduced pathological tau spread into downstream hippocampus. These data strongly support the hypothesis that in Alzheimer's disease (AD), Aß-associated hyperactivity accelerates the progression of pathological tau along vulnerable neuronal circuits, and demonstrates the utility of chronic, neuromodulatory approaches in ameliorating AD pathology in vivo.


Assuntos
Doença de Alzheimer/genética , Precursor de Proteína beta-Amiloide/genética , Córtex Entorrinal/metabolismo , Tauopatias/genética , Proteínas tau/genética , Potenciais de Ação/fisiologia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Doença de Alzheimer/terapia , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/genética , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Dependovirus/genética , Dependovirus/metabolismo , Modelos Animais de Doenças , Eletrodos Implantados , Córtex Entorrinal/patologia , Feminino , Regulação da Expressão Gênica , Vetores Genéticos/química , Vetores Genéticos/metabolismo , Hipocampo/metabolismo , Hipocampo/patologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neurônios/metabolismo , Neurônios/patologia , Agregados Proteicos , Técnicas Estereotáxicas , Tauopatias/metabolismo , Tauopatias/patologia , Tauopatias/terapia , Ritmo Teta/fisiologia , Transdução Genética , Transgenes , Proteínas tau/metabolismo
15.
Sheng Li Xue Bao ; 72(4): 449-454, 2020 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-32820307

RESUMO

The paper was aimed to explore the role of serum exosomes induced by hepatic ischemia/reperfusion (I/R) injury in the damage of hippocampus and cerebral cortex of rats. The male Sprague-Dawley (SD) rats were randomly divided into 4 groups: sham operation group (S), hepatic I/R injury group (I/R), serum exosomes from S group treatment group (ES) and serum exosomes from I/R group treatment group (EI). In ES group and EI group, 100 µL serum exosomes from S group and I/R group were injected into the normal rats through tail vein respectively. Another three normal rats were injected intravenously with serum exosomes labeled with PKH26 red fluorescence, and then the expression of fluorescence in the brain tissues was observed by immunofluorescence microscope. The morphology and size of exosomes were observed by transmission electron microscope, the expression of exosomes markers CD63 and CD9 was detected by Western blot, and the damage of liver and brain, levels of apoptosis and oxidative stress response in hippocampus and cerebral cortex were observed by serological and histological indexes. The results showed that the exosomes were a group of round or ovoid membranous vesicles, sized in 30-100 nm. Compared with that in S group, the content of serum exosomes in I/R group was increased (P < 0.05). Moreover, serum exosomes could go through the blood-brain barrier and enter the brain tissue freely through blood circulation. The index of liver function in I/R group was significantly higher than that in S group (P < 0.05). There was no significance in the degree of brain damage, apoptosis and oxidative stress in hippocampus and cerebral cortex between S group and ES group. Compared with those in S group and ES group, the serum levels of brain injury markers, apoptosis index (AI) and oxidative stress in hippocampus and cerebral cortex increased in I/R group and EI group (P < 0.05). Whereas, compared with those in I/R group, the above indicators in EI group decreased (P < 0.05). Therefore, hepatic I/R injury can lead to the damage of hippocampus and cerebral cortex, and the increased serum exosomes induced by hepatic I/R plays an important role.


Assuntos
Isquemia Encefálica , Exossomos , Traumatismo por Reperfusão , Animais , Hipocampo , Fígado , Masculino , Ratos , Ratos Sprague-Dawley
16.
Sheng Li Xue Bao ; 72(4): 463-474, 2020 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-32820309

RESUMO

Formaldehyde is one of the simplest organic small molecules containing C, H and O elements in the early stage of earth's evolution; however, it has been found to be existed in every eukaryotic cell and participate in "one carbon metabolism". Recent studies have shown that formaldehyde may act as a signal molecule to regulate memory formation. After electrical stimulation or learning activity, the levels of formaldehyde in rat brains were increased instantly, and N-methyl-D-aspartate (NMDA) receptor was activated to promote the formation of long-term potentiation (LTP) or spatial memory. On the contrary, after reducing the levels of formaldehyde in the brains, NMDA receptor could not be activated, which was accompanied by the deficits in both LTP and memory. Moreover, in the brains of normal aged rats and APP/PS1 transgenic mice, the concentrations of formaldehyde were abnormally increased, which directly inhibited NMDA receptor activity and impaired spatial memory. This article reviewed the physiological and pathophysiological functions of endogenous formaldehyde in learning and memory.


Assuntos
Potenciação de Longa Duração , Memória , Animais , Formaldeído , Hipocampo , Aprendizagem em Labirinto , Transtornos da Memória , Camundongos , Ratos , Receptores de N-Metil-D-Aspartato
17.
Sheng Li Xue Bao ; 72(4): 455-462, 2020 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-32820308

RESUMO

The aim of the present study was to observe the expression of pyroptosis- and inflammation-related proteins in the hippocampus of mice with insulin resistance (IR) after aerobic exercise, and to explore the possible mechanism of exercise to improve IR. C57BL/6J male mice of 6 weeks old were randomly fed with normal diet (n = 12) and high-fat diet (HFD) (n = 26) for 12 weeks respectively. Glucose tolerance test (GTT) and insulin tolerance test (ITT) were performed to determine whether IR occurred in HFD mice. Then the mice were randomly divided into control group (n = 12), IR group (n = 10) and IR + aerobic exercise group (AE, n = 10). Mice in AE group performed a 12-week progressive speed treadmill training after being adapted to the treadmill for one week. After the intervention, the expression of pyroptosis- and inflammation-related proteins in hippocampus was detected by Western blot. The results showed that compared with control group, NFκB, Nod-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing CARD (ASC), pyroptosis-related proteins like pro-Caspase-1, gasdermin D (GSDMD), GSDMD-N, and inflammatory factors IL-1ß, IL-18 were significantly increased. The inflammasome-related protein NIMA-related kinase 7 (NEK7) and pyroptosis-related protein Caspase-1 showed an increasing trend, but there was no significant difference. Compared with the IR group, progressive speed treadmill training significantly reduced the expression of NFκB, NLRP3, NEK7, ASC, pro-Caspase-1, GSDMD, GSDMD-N, IL-1ß, and IL-18 in the hippocampus of mice with IR. These results suggested 12-week progressive speed treadmill training can significantly reduce the expression of pyroptosis-related proteins and inflammatory factors in the hippocampus of mice with IR, and inhibit pyroptosis.


Assuntos
Expressão Gênica , Inflamassomos , Resistência à Insulina , Condicionamento Físico Animal , Piroptose , Animais , Caspase 1 , Hipocampo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Quinases Relacionadas a NIMA , Proteína 3 que Contém Domínio de Pirina da Família NLR
18.
PLoS Biol ; 18(8): e3000826, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32776935

RESUMO

Ca2+/calmodulin-dependent kinase II (CaMKII) regulates synaptic plasticity in multiple ways, supposedly including the secretion of neuromodulators like brain-derived neurotrophic factor (BDNF). Here, we show that neuromodulator secretion is indeed reduced in mouse α- and ßCaMKII-deficient (αßCaMKII double-knockout [DKO]) hippocampal neurons. However, this was not due to reduced secretion efficiency or neuromodulator vesicle transport but to 40% reduced neuromodulator levels at synapses and 50% reduced delivery of new neuromodulator vesicles to axons. αßCaMKII depletion drastically reduced neuromodulator expression. Blocking BDNF secretion or BDNF scavenging in wild-type neurons produced a similar reduction. Reduced neuromodulator expression in αßCaMKII DKO neurons was restored by active ßCaMKII but not inactive ßCaMKII or αCaMKII, and by CaMKII downstream effectors that promote cAMP-response element binding protein (CREB) phosphorylation. These data indicate that CaMKII regulates neuromodulation in a feedback loop coupling neuromodulator secretion to ßCaMKII- and CREB-dependent neuromodulator expression and axonal targeting, but CaMKIIs are dispensable for the secretion process itself.


Assuntos
Astrócitos/metabolismo , Fator Neurotrófico Derivado do Encéfalo/genética , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/genética , Cálcio/metabolismo , Neurônios/metabolismo , Subunidades Proteicas/genética , Animais , Astrócitos/citologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/deficiência , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Retroalimentação Fisiológica , Regulação da Expressão Gênica , Hipocampo/citologia , Hipocampo/metabolismo , Camundongos , Camundongos Transgênicos , Neurônios/citologia , Fosforilação , Cultura Primária de Células , Subunidades Proteicas/deficiência , Sinapses/fisiologia , Transmissão Sináptica , Imagem com Lapso de Tempo
19.
Toxicol Lett ; 332: 192-201, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-32693020

RESUMO

Fenvalerate, a synthetic pyrethroid insecticide, is an environmental endocrine disruptor and neurodevelopmental toxicant. An early report found that pubertal exposure to high-dose fenvalerate impaired cognitive and behavioral development. Here, we aimed to further investigate the effect of pubertal exposure to low-dose fenvalerate on cognitive and behavioral development. Mice were orally administered with fenvalerate (0.2, 1.0 and 5.0 mg/kg) daily from postnatal day (PND) 28 to PND56. Learning and memory were assessed by Morris water maze. Anxiety-related activities were detected by open-field and elevated plus-maze. Increased anxiety activities were observed only in females exposed to fenvalerate. Spatial learning and memory were damaged only in females exposed to fenvalerate. Histopathology observed numerous scattered shrinking neurons and nuclear pyknosis in hippocampal CA1 region. Neuronal density was reduced in hippocampal CA1 region of fenvalerate-exposed mice. Mechanistically, hippocampal thyroid hormone receptor (TR)ß1 was down-regulated in a dose-dependent manner in females. In addition, TRα1 was declined only in females exposed to 5.0 mg/kg fenvalerate. Taken together, these suggests that pubertal exposure to low-dose fenvalerate impairs cognitive and behavioral development in a gender-dependent manner. Hippocampal TR signaling may be, at least partially, involved in fenvalerate-induced impairment of cognitive and behavioral development.


Assuntos
Transtornos Cognitivos/induzido quimicamente , Hipocampo/metabolismo , Inseticidas/toxicidade , Nitrilos/toxicidade , Piretrinas/toxicidade , Transdução de Sinais/efeitos dos fármacos , Hormônios Tireóideos , Animais , Ansiedade/induzido quimicamente , Ansiedade/psicologia , Peso Corporal/efeitos dos fármacos , Região CA1 Hipocampal/efeitos dos fármacos , Região CA1 Hipocampal/metabolismo , Transtornos Cognitivos/psicologia , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Disruptores Endócrinos , Feminino , Hipocampo/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Neurônios/patologia , Receptores dos Hormônios Tireóideos/efeitos dos fármacos , Caracteres Sexuais
20.
Bratisl Lek Listy ; 121(8): 580-583, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32726121

RESUMO

OBJECTIVES: We investigated the effect of low, medium and high doses of oral vitamin A, on the number of fetal hippocampal neurons. BACKGROUND: High doses of vitamin A during pregnancy may cause embryonic malformations. There are reports about dosages that don't cause macroscopic malformations, but may cause mental and behavioral disorders. Still, quantitative morphological studies explaining this topic are lacking. METHODS: We administered oral vitamin A to pregnant rats on the 10th-12th days of pregnancy at doses of 10000, 20000, 30000, 40000, 50000, 100000 and 200000 IU/kg. We collected the fetuses on the 19th day and removed their brains. After staining with cresyl violet and immunolabeling with Tunel and Ki67 antibody, we examined the hippocampi with stereological methods. RESULTS: Vitamin A decreased hippocampal neuron numbers beginning from 20000 IU/kg. While the number of Ki67 positive cells increased with the dosage, the increase of apoptotic cells begun at the dose of 50000 IU/kg. CONCLUSION: Our study demonstrates that vitamin A, beginning from the dosage of 20000 IU/kg, is decreasing the total hippocampal neuron numbers during the critical period of embryonic brain development and that apoptosis may not be the only factor in this outcome (Tab. 1, Fig. 3, Ref. 27).


Assuntos
Hipocampo , Neurônios , Vitamina A , Vitaminas , Animais , Apoptose , Feminino , Hipocampo/efeitos dos fármacos , Marcação In Situ das Extremidades Cortadas , Neurônios/efeitos dos fármacos , Gravidez , Ratos , Vitamina A/farmacologia , Vitaminas/farmacologia
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