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1.
Life Sci ; 245: 117386, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-32006528

RESUMO

AIMS: Steroid receptor coactivator-1 (SRC-1) is a key coactivator for the efficient transcriptional activity of steroids in the regulation of hippocampal functions. However, the effect of SRC-1 on hippocampal memory processes remains unknown. Our aim was to investigate the roles of hippocampal SRC-1 in the consolidation and reconsolidation of contextual fear memory in mice. MAIN METHODS: Contextual fear conditioning paradigm was constructed in adult male C57BL/6 mice to examine the fear learning and memory processes. Adeno-associated virus (AAV) vector-mediated RNA interference (RNAi) was infused into hippocampus to block hippocampal SRC-1 level. Immunofluorescent staining was used to detect the efficiency of transfection. High plus maze and open field test were used to determine anxiety and locomotor activity. Western blot analyses were used to detect the expression of SRC-1 and synaptic proteins in the hippocampus. KEY FINDINGS: We first showed that the expression of SRC-1 was regulated by fear conditioning training in a time-dependent manner, and knockdown of SRC-1 impaired contextual fear memory consolidation without affecting innate anxiety or locomotor activity. In addition, hippocampal SRC-1 was also regulated by the retrieval of contextual fear memory, and downregulation of SRC-1 disrupted fear memory reconsolidation. Moreover, knockdown of SRC-1 reversed the increased GluR1 and PSD-95 levels induced by contextual fear memory retrieval. SIGNIFICANCE: Our data indicate that hippocampal SRC-1 is required for the consolidation and reconsolidation of contextual fear memory, and SRC-1 may be a potential therapeutic target for mental disorders that are involved in hippocampal memory dysfunction.


Assuntos
Medo/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Memória/efeitos dos fármacos , Coativador 1 de Receptor Nuclear/antagonistas & inibidores , Animais , Western Blotting , Condicionamento Clássico/efeitos dos fármacos , Condicionamento Clássico/fisiologia , Medo/fisiologia , Medo/psicologia , Imunofluorescência , Hipocampo/fisiologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Coativador 1 de Receptor Nuclear/fisiologia
2.
Food Chem Toxicol ; 135: 111055, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31838190

RESUMO

This study explored the camel milk (CM) efficacy to ameliorate the fenpropathrin (FNP) induced neurotoxic impacts in rats. Six groups were orally administered physiological saline, corn oil, CM (2ml/rat/day), FNP (15 mg/kg bw daily for 60 days), CM/FNP (protective) or FNP + CM (therapeutic). Sensorimotor functions, memory, exploratory, and locomotor activities were assessed. The levels of dopamine (DOPA) neurotransmitter, acetylcholinesterase (AChE) enzyme, oxidative stress, and inflammatory markers were determined. Brain histopathology and apoptotic markers immunohistochemical detection were performed. The results revealed that FNP exposure resulted in deficit sensorimotor functions, impaired memory, and less exploration. DOPA and AChE Levels were significantly reduced. FNP exposure increased nitric oxide, malondialdehyde, myeloperoxidase, Caspase-3, and tumor necrosis factor-alpha levels but interleukin 10, total antioxidant capacity, and Bcl-2 levels were declined. Also, FNP exposure induced obvious encephalopathy. Additionally, neurodegenerative changes were seen in the hippocampi of FNP-treated rats. FNP Exposure induced a significant decrease of Bcl-2 immunolabelling but Caspase-3 immunoexpression was increased in cerebral cortices and hippocampus tissues. CM significantly counteracted the FNP injurious impacts, especially when used as a prophylactic routine than a therapeutic one. Conclusively, these findings confirmed that CM could be a biologically effective protective agent against FNP induced neurobehavioral aberrations and neurotoxic impacts.


Assuntos
Apoptose , Encéfalo/efeitos dos fármacos , Leite , Estresse Oxidativo , Piretrinas/toxicidade , Animais , Comportamento Animal/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Camelus , Relação Dose-Resposta a Droga , Inflamação/induzido quimicamente , Masculino , Memória/efeitos dos fármacos , Síndromes Neurotóxicas , Piretrinas/administração & dosagem , Ratos , Ratos Sprague-Dawley
3.
J Pharm Biomed Anal ; 177: 112840, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31522096

RESUMO

Alzheimer's disease (AD) is the most widespread neurodegenerative disease; there are around ten million new cases of Alzheimer yearly worldwide especially in middle or low-income countries. Pistacia is a genus of flowering plants including the well-known, economically important P. chinensis Bunge, P. lentiscus L. and P. khinjuk. In this study, the metabolic profiling of Pistacia leaves extracts was achieved via UHPLC-ESI-MS analysis and GC-MS analysis employing chemometric analysis for their discrimination. In addition, the methanolic extracts of different Pistacia species were assessed for their anti-cholinesterase and anti-inflammatory activities by various in vitro assays. 37 and 30 metabolites belonging to different classes were identified by UHPLC-ESI-MS and GC-MS analyses respectively. Chemometric analysis revealed that P. lentiscus and P. khinjuk were more closely related chemically to each other. All studied Pistacia leaves extracts showed apparent anti-cholinesterase and anti-inflammatory activities, which promotes their use in the prevention and management of AD.


Assuntos
Anti-Inflamatórios/farmacologia , Inibidores da Colinesterase/farmacologia , Memória/efeitos dos fármacos , Pistacia/química , Extratos Vegetais/farmacologia , Acetilcolinesterase/metabolismo , Doença de Alzheimer/tratamento farmacológico , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Inibidores da Colinesterase/química , Inibidores da Colinesterase/isolamento & purificação , Cromatografia Líquida de Alta Pressão/métodos , Ensaios Enzimáticos , Eritrócitos , Proteínas Ligadas por GPI/antagonistas & inibidores , Proteínas Ligadas por GPI/metabolismo , Cromatografia Gasosa-Espectrometria de Massas/métodos , Voluntários Saudáveis , Hemólise/efeitos dos fármacos , Humanos , Metabolômica/métodos , Óleos Voláteis/química , Óleos Voláteis/isolamento & purificação , Óleos Voláteis/farmacologia , Pistacia/metabolismo , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Folhas de Planta/metabolismo , Óleos Vegetais/química , Óleos Vegetais/isolamento & purificação , Óleos Vegetais/farmacologia , Espectrometria de Massas por Ionização por Electrospray/métodos
4.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(6): 852-858, 2019 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-31880117

RESUMO

OBJECTIVE: To investigate the protection effect of dexamethasone (DXMS) on the memory impairment and neuronal damage of neonate rats that caused by sevoflurane (SEVO) exposure. METHODS: 5-days-old newborn SD rats were randomly divided into normal group (NC group) (10 rats), SEVO group (10 rats) and SEVO+DXMS group (10 rats). Rats of SEVO group and SEVO+DXMS group were exposed to 2.5% SEVO 2 h per day for 1 week, meanwhile the rats of SEVO+DXMS group were given 20 mg/kg DXMS treatment before exposure and the normal group was given the same amount of placebo and carrier gas as control. All rats were fed normally till infancy. Then the Morris water maze test was used to assess the learning and memory function of rats of each group. HE and Nissl staining were used to observe the histomorphology and neuronal changes in the hippocampus of rats. ELISA was performed to test the changes in nitric oxide (NO), superoxide dismutase (SOD) and malondialdehyde (MDA) level in brain tissues. The expression of silent information regulator 1 (SIRT1), peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), fork head protein transcription factor 3α (FOXO3α) mRNA in brain tissue was detected by qRT-PCR. Western blot was used to explore the changes in SIRT1 and caspase-3 protein expression of hippocampus. RESULTS: Compared with the NC group, the pathologic damage of hippocampus tissues was severely in SEVO group, and the number of neuronal cells was decreased as well. After SEVO intervention, the degree of pathologic damage was alleviated, and the number of neuronal cells was significantly increased. The Morris water maze test showed that the escape latency, number of platform crossing and target quadrant retention time between SEVO group and SEVO+DXMS group were significant different. The level of NO and MDA in brain of SEVO+DXMS group was significantly decreased than that of SEVO group, while the level of SOD was increased. qRT-PCR showed that the mRNA levels of SIRT1, PGC-1α and FOXO3α in SEVO+DXMS group were significantly higher those in SEVO group, but mRNA level of SIRT1 was still significantly lower than that of NC group. Western blot showed that the expression of SIRT1 protein in SEVO+DXMS group was significantly higher than that of SEVO group, and the expression of caspase-3 was reduced in SEVO+DXMS compared with SEVO group. CONCLUSION: DXMS could reduce the level of oxidative stress and suppress the apoptosis of neuronal cells, reduce SEVO-induced brain damage in neonatal rats and improve learning and memory ability in infant rats.


Assuntos
Memória/efeitos dos fármacos , Animais , Dexametasona , Hipocampo , Aprendizagem em Labirinto , Ratos , Ratos Sprague-Dawley , Sevoflurano
5.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 35(4): 359-362, 2019 Jul 28.
Artigo em Chinês | MEDLINE | ID: mdl-31701723

RESUMO

OBJECTIVE: To investigate the effects of berberine on learning and memory ability in vascular cognitive impairment rats. METHODS: Sixty-eight Wistar rats were randomly divided into control group (n=10), sham operated group (n=10) and the modeling group of vascular cognitive impairment rat (n=48), then the rats in modeling group were randomly divided into four groups (n=10): vehicle group, berberine low dose group (20 mg/kg), medium dose group (40 mg/kg) and high dose group (60 mg/kg). Bilateral common carotid arteries were occluded in rats to establish vascular cognitive impairment (VCI) model. Different doses of berberine were intraperitoneally injected into the treatment group and normal saline was intraperitoneally injected into the other groups once a day for a total of 34 days. After 28 days of administration, Morris water maze was used to test the learning and memory ability of rats. After the water maze experiment, the levels of superoxide dismutase (SOD) activity, glutathione (GSH), malondialdehyde (MDA), tumor necrosis factor alpha(TNF-α), interleukin-1 beta (IL-1ß), 5-hydroxytryptamine (5-HT) and monoamine oxidase (MAO) in the forebrain cortex were detected. RESULTS: Compared to sham group, the escape latency in VCI group was significantly extended (P<0.01) and the times of passing through the platform were decreased remarkably (P<0.01). The levels of SOD, GSH and 5-HT in the hippocampus or anterior cortex were decreased significantly (P<0.01), while the contents of MDA, TNF-α, IL-1ß and MAO were increased remarkably (P<0.01). Compared with VCI group, the escape latency in berberine-treated groups was shortened significantly (P<0.01, P<0.05) and the times of passing through the platform were increased remarkably (P<0.01, P<0.05), the levels of SOD, GSH and 5-HT were increased significantly (P<0.01), while the contents of TNF-α, IL-1ß and MAO were decreased remarkably (P<0.01). CONCLUSION: Berberine could significantly improve the spatial learning and memory abilities of rats with vascular cognitive impairment. The mechanism may be related to the effects of berberine on the hippocampal antioxidant stress, anti-inflammatory response and the monoamine neurotransmitter system in the forebrain cortex. Berberine 60 mg/kg dose group had better effect.


Assuntos
Berberina/farmacologia , Disfunção Cognitiva/tratamento farmacológico , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Animais , Hipocampo , Inflamação , Estresse Oxidativo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Ratos Wistar
6.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 35(4): 366-370, 2019 Jul 28.
Artigo em Chinês | MEDLINE | ID: mdl-31701725

RESUMO

OBJECTIVE: To investigate the effects of Acorus tatarinowii Schott and its active component 5- hydroxymethyl furfural (HMF) on learning and memory and ERK/CREB signal in hippocampus of rats with exercise-induced fatigue. METHODS: SD rats were randomly divided into normal group (A), exercise group (B), exercise + HMF low, middle and high dose treatment group (C, D, E), exercise + acorus tatarinowii Schott low, middle and high dose treatment group (F, G, H), with ten rats in each group. The rats in group C, D and E were treated with HMF at the doses of 0.10, 1.00 and 3.00 mg. kg-1 by ig. The rats in group F, G and H were treated with the extracts of Acorus tatarinowii Schott at the doses of 0.12, 1.20 and 4.80 g. kg-1 by ig. Learning and memory of rats were tested by the method of water maze experiment, and the expression levels of p-ERK1/2 and p-CREB protein in hippocampus of rats were tested by the method of Western blot in the end of the experiment. RESULTS: The escape latencies of E and H groups were lower than those of groups B, C, D, F and G; and the numbers of plateau crossing were more than those of groups B, C, D, F and G and the expression levels of p-ERK1/2, p-CREB protein were higher than those of groups B, C, D, F and G , respectively(P < 0.01). There was no significant difference in the above indexes among groups A, E and H(P>0.05) except that the expression levels of p-ERK2 protein in group E were lower than those in group A and H (P<0.05). CONCLUSION: Acorus tatarinowii and its active component- HMF can improve the learning and memory of rats with exercise-induced fatigue, and the mechanism is related to the up-regulation of ERK / CREB signal in hippocampus of rats with exercise-induced fatigue.


Assuntos
Acorus/química , Fadiga/tratamento farmacológico , Furaldeído/análogos & derivados , Condicionamento Físico Animal , Animais , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Furaldeído/farmacologia , Hipocampo/metabolismo , Sistema de Sinalização das MAP Quinases , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Compostos Fitoquímicos/farmacologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
7.
J Agric Food Chem ; 67(49): 13767-13774, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31722531

RESUMO

Recent studies indicated that neuroinflammation contributes to the exacerbation of Alzheimer's disease (AD) and plays an important role in AD. The NOD-like receptor protein 3 (NLRP3) inflammasome, which is an important component of innate immune system, is associated with a wide range of human central nervous system disorders, including AD. Most of the studies focus on the protective effects of docosahexaenoic acid (DHA) in AD, but eicosapentaenoic acid (EPA) has rarely been involved. Here, we investigate the effects of EPA in the forms of phosphatidylcholine (EPA-PC) and ethyl esters (EPA-EE) in improving Aß1-42-induced neurotoxicity. The spatial memory ability and the biochemical changes in the hippocampus were measured, including glial cell activation, tumor necrosis factor α production, NLRP3 inflammasome activation, and autophagic flux. The present results showed that the AD rats were significantly protected from spatial memory loss by the supplementation (EPA + DHA = 60 mg/kg, i.g., 20 days) of EPA-PC, while EPA-EE showed no significant benefit. Further mechanism studies suggested that EPA-PC could inhibit Aß-induced neurotoxicity by alleviating NLRP3 inflammasome activation and enhancing autophagy. These findings indicate that EPA could improve cognitive deficiency in Aß1-42-induced AD rats via autophagic inflammasomal pathway and the bioactivity differs in its molecular form.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/toxicidade , Autofagia/efeitos dos fármacos , Ácido Eicosapentaenoico/administração & dosagem , Inflamassomos/efeitos dos fármacos , Fosfatidilcolinas/administração & dosagem , Doença de Alzheimer/metabolismo , Doença de Alzheimer/fisiopatologia , Doença de Alzheimer/psicologia , Peptídeos beta-Amiloides/metabolismo , Animais , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Humanos , Inflamassomos/genética , Inflamassomos/metabolismo , Masculino , Memória/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
8.
Life Sci ; 239: 117076, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31751578

RESUMO

Waterpipe tobacco smoking (WP) is associated with a vast range of detrimental health effects, including memory impairment and anti-oxidative scavenging dysfunction. Forced swimming exercise (FSE) is known to improve cognitive function and general wellbeing. In this study, we evaluated the neuroprotective effect of FSE on memory impairment induced by exposure to WP in the rat model. Wistar male rats were divided into four groups: fresh air (control), WP exposure, FSE, and WP/FSE. Animals were exposed to WP for 1 h/day, 5 days/week for 4 weeks. At the same time, animals were forced to swim 1 h/day as 5 min swimming followed by 5 min rest, 5 days/ week for 4 weeks. Spatial learning and memory was assessed using Radial Arm Water Maze (RAWM). Additionally, hippocampal oxidative stress biomarkers including reduced glutathione (GSH), oxidized glutathione (GSSG), GSH/GSSG ratio, glutathione peroxidase (GPx), Catalase, and TBARS were analyzed. Key findings: this study showed that WP exposure impaired both short- and long-term memory (P < 0.05). On the other hand, FSE prevented memory impairment induced by WP exposure (P < 0.05). Moreover, WP exposure reduced activity of catalase, GPx, and GSH/GSSG ratio (P < 0.05) in the hippocampus, which were also normalized by FSE. However, no changes were detected in GSH and TBARS levels in WP exposure and/or FSE groups. In conclusion, WP exposure induced both short- and long- term memory impairments, which was prevented by FSE. This improvement in memory function might be attributed to oxidative stress biomarkers pathways.


Assuntos
Memória/efeitos dos fármacos , Esforço Físico/efeitos dos fármacos , Tabaco para Cachimbos de Água/efeitos adversos , Animais , Antioxidantes/farmacologia , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Hipocampo/metabolismo , Masculino , Transtornos da Memória/tratamento farmacológico , Memória de Longo Prazo/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Condicionamento Físico Animal/métodos , Ratos , Ratos Wistar , Cachimbos de Água , Superóxido Dismutase/metabolismo , Natação/fisiologia , Fumar Tabaco/efeitos adversos
9.
J Toxicol Sci ; 44(10): 681-691, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31588059

RESUMO

Zinc (Zn) is an essential element, but excess amounts are known to cause neurotoxic effects. The risk of excessive Zn intake is increased by supplementing food intake with dietary supplements. Ageing affects many cellular processes that predispose individuals to neurodegeneration. Indeed, the prevalence of senile dementia such as Alzheimer's disease, Parkinson's disease, and vascular-type dementia increases with age. As such, we investigated the effects of long-term exposure to excess Zn on learning and memory in aged mice. ICR-JCL female mice (aged 26 weeks) were administered 0, 200, or 500 ppm Zn as zinc chloride in drinking water for 30 weeks. After 30-week administration, aged female animals were subjected to Y-maze, novel object recognition, and step-through passive avoidance tests. Chronic exposure to Zn did not inhibit learning and memory in the Y-maze test, but dose-dependently inhibited learning and memory in novel object recognition and step-through passive avoidance tests. These results indicate the potential for chronic Zn exposure to dose-dependently inhibit both long-term and novel object recognition memory. Results of microarray analysis revealed significant changes in gene expression of transthyretin and many olfactory receptors in the hippocampus of Zn-treated mice.


Assuntos
Cloretos/toxicidade , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Síndromes Neurotóxicas , Compostos de Zinco/toxicidade , Envelhecimento , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Feminino , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Síndromes Neurotóxicas/genética , Transcriptoma/efeitos dos fármacos
10.
Neurol Res ; 41(11): 1008-1014, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31573411

RESUMO

Objective: To investigate the effects of propofol used in early pregnancy on brain development and function of offspring, and further to explore the effects of docosahexaenoic acid (DHA) intervention. Methods: Forty pregnant rats were randomly divided into four groups: control group (C), propofol group (P), DHA intervention group (D), and propofol + DHA group (P + D). The DHA treatment was before propofol was administered. Morris water maze test was performed 30 days after delivery. The levels of amyloid beta (Aß), IL-1ß and reactive oxygen species (ROS) in hippocampus were detected by enzyme-linked immunosorbent assay (ELISA). The expression of brain-derived neurotrophic factor (BDNF) and tyrosine kinase-B (Trk-B), protein kinase B (Akt), p-Akt and cAMP response element-binding protein (CREB) in hippocampus were detected by western blot. Results: The learning and memory abilities of the rats in P group were reduced. The levels of Aß, IL-1ß and ROS were increased, while the levels of BDNF, Trk-B and CREB, and p-Akt/Akt ratio were reduced. In addition, compared with P group, DHA in P + D group reversed or alleviated adverse changes caused by propofol. Conclusions: Application of general anesthesia with propofol during the early stage of pregnancy can negatively affect the brain development of the offspring to reduce the learning and memory ability, while DHA can reverse it.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Ácidos Docosa-Hexaenoicos/farmacologia , Memória/efeitos dos fármacos , Propofol/farmacologia , Anestesia Geral/métodos , Animais , Animais Recém-Nascidos , Encéfalo/crescimento & desenvolvimento , Feminino , Hipocampo/efeitos dos fármacos , Aprendizagem em Labirinto/efeitos dos fármacos , Gravidez , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
11.
Artigo em Inglês | MEDLINE | ID: mdl-31597243

RESUMO

Bisphenol A (BPA) is a major constituent of plastic products, including epoxy resin containers, mobile phones, dental sealants, as well as electronic and medical equipment. BPA is recognized as an endocrine system-disrupting chemical which has toxic effects on the brain and reproductive system. However, little is known about the effects of co-exposure of BPA with allergens on the memory function and neurological as well as immunological biomarker levels. In this study, we examined the effects of intratracheal instillation of BPA on the memory function and neuroimmune biomarker levels using a mouse model of allergic asthma. Male C3H/HeJ Jcl mice were given three doses of BPA (0.0625 pmol, 1.25 pmol, and 25 pmol BPA/animal) intratracheally once a week, and ovalbumin (OVA) intratracheally every other week from 5 to 11 weeks old. At 11 weeks of age, a novel object recognition test was conducted after the final administration of OVA, and the hippocampi and hypothalami of the animals were collected after 24 h. The expression levels of the memory function-related genes N-methyl-D-aspartate (NMDA) receptor subunits, inflammatory cytokines, microglia markers, estrogen receptor-alpha, and oxytocin receptor were examined by real-time RT-PCR (real-time reverse transcription polymerase chain reaction) and immunohistochemical methods. Impairment of the novel object recognition ability was observed in the high-dose BPA-exposed mice with allergic asthma. In addition, the allergic asthmatic mice also showed downregulation of neurological biomarkers, such as NMDA receptor subunit NR2B in the hippocampus but no significant effect on immunological biomarkers in the hypothalamus. These findings suggest that exposure to high-dose BPA triggered impairment of memory function in the allergic asthmatic mice. This is the first study to show that, in the presence of allergens, exposure to high-dose BPA may affect memory by modulating the memory function-related genes in the hippocampus.


Assuntos
Poluentes Ocupacionais do Ar/efeitos adversos , Poluentes Atmosféricos/toxicidade , Asma/imunologia , Compostos Benzidrílicos/toxicidade , Biomarcadores/sangue , Biomarcadores/metabolismo , Memória/efeitos dos fármacos , Fenóis/toxicidade , Animais , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Endogâmicos C3H
12.
Ecotoxicology ; 28(9): 1056-1062, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31512041

RESUMO

While the ecological effects of pesticides have been well studied in honeybees, it is unclear to what extent other anthropogenic contaminants such as air pollution may also negatively affect bee cognition and behaviour. To answer this question, we assessed the impacts of acute exposure to four ecologically relevant concentrations of a common urban air pollutant-diesel generated air pollution on honeybee odour learning and memory using a conditioned proboscis extension response assay. The proportion of bees that successfully learnt odours following direct air pollution exposure was significantly lower in bees exposed to low, medium and high air pollutant concentrations, than in bees exposed to current ambient levels. Furthermore, short- and long-term odour memory was significantly impaired in bees exposed to low medium and high air pollutant concentrations than in bees exposed to current ambient levels. These results demonstrate a clear and direct cognitive cost of air pollution. Given learning and memory play significant roles in foraging, we suggest air pollution will have increasing negative impacts on the ecosystem services bees provide and may add to the current threats such as pesticides, mites and disease affecting colony fitness.


Assuntos
Poluição do Ar/efeitos adversos , Abelhas/efeitos dos fármacos , Percepção Olfatória/efeitos dos fármacos , Animais , Abelhas/fisiologia , Cidades , Aprendizagem/efeitos dos fármacos , Memória/efeitos dos fármacos
13.
Pol J Vet Sci ; 22(3): 481-487, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31560462

RESUMO

Therefore, the aim of the present study was to evaluate the possible effect of bilberry fruit (Vaccinium myrtillus L.) supplement in a daily diet on the cognitive behaviour of the rats and the expression of paravalbumin (PV) in populations of hippocampal neurons. It has been postulated that the antioxidants present in bilberry fruit may act as neuroprotective factors playing also a significant role as memory enhancements. Forty Wistar rats with a similar average body weight (460 ± 0.4 g) were divided into four groups (n=10 per group). The control group received standard feed (210 g/week), whereas animals of experimental groups received standard feed supplemented with bilberry (per os) at consumed doses of 2 g (group I), 5 g (group II), and 10 g/kg b.w./ /day (group III). After three months of feeding with bilberry, the modified elevated plus-maze test (mEPM) was performed. After 32 weeks of feeding, brains were collected and PV-immunoreactive (ir) neurons were immunohistochemically visualized. In the modified elevated plus-maze test, transfer latency examined 2 h and 24 h after the acquisition session was significantly shorter (p⟨0.05) in the group II in comparison with the control group. In CA1 and CA2/CA3 hippocampal fields as well as dentate gyrus of all experimental groups, a significant (p⟨0.05) decrease in number of PV-ir neurons were found. In relation to the control group, the mean subpopulation of PV-ir neurons found in groups II and III were significantly reduced. The subpopulations of PV-ir neurons found in DG of all experimental groups were significantly reduced in comparison to the control. In conclusion the in the present paper we demonstrated a relationship between the diet rich in a bilberry fruit and process of memory as well as numbers of calcium- binding protein-expressing hippocampal neurons. Our results may be source of basic knowledge for further research aiming at neuroprotective role of the bilberry fruit.


Assuntos
Frutas , Hipocampo/efeitos dos fármacos , Memória/efeitos dos fármacos , Parvalbuminas/metabolismo , Vaccinium myrtillus , Ração Animal/análise , Animais , Encéfalo/anatomia & histologia , Encéfalo/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Tamanho do Órgão , Parvalbuminas/genética , Ratos
14.
Sci Total Environ ; 697: 134036, 2019 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-31476513

RESUMO

To investigate the developmental neurotoxicity of environmental bisphenol A (BPA) exposure for infants and children, postnatal rats were used as the animal model and were divided into four groups. Then, they were treated with different concentrations of BPA (i.e., 0, 0.5, 50, or 5000 µg/kg·bw/day of BPA as the control, low-, medium- and high-exposed group) from postnatal days 7 to 21. Y-maze tests, Golgi-Cox assays and liquid chromatography-tandem mass spectrometry (LC/MS/MS) were performed to test the changes of learning and memory ability, hippocampal neuromorphology and neurotransmitter levels, respectively. The results showed that the BPA-exposed rats, especially the low- and high-exposed rats, needed more trials and longer times to qualify for the learned criterion than the control rats. Additionally, rats after low- or high-exposure to BPA exhibited decreased DG dendritic complexity and reduced CA1 and DG dendritic spine densities in the hippocampus. Low-dosage BPA treatment could significantly alter the neurotransmitter contents in the hippocampus. In male rats, the levels of glutamic acid (Glu) and acetylcholine increased, while the 5-hydroxytryptamine (5-HT) and γ-aminobutyric acid (GABA) levels decreased, which lead to an unbalanced Glu/GABA ratio. However, in female rats, only 5-HT levels decreased. In conclusion, postnatal exposure to BPA could sex- and dose-dependently disrupt dendritic development and neurotransmitter homeostasis in the rat hippocampus. The impaired spatial learning and memory ability of rats induced by low-dose BPA is associated with both disrupted dendritic development and neurotransmitter homeostasis in the hippocampus.


Assuntos
Compostos Benzidrílicos/toxicidade , Encéfalo/efeitos dos fármacos , Disruptores Endócrinos/toxicidade , Neurotransmissores/metabolismo , Fenóis/toxicidade , Animais , Comportamento Animal/efeitos dos fármacos , Memória/efeitos dos fármacos , Ratos , Testes de Toxicidade
15.
J Pharmacol Sci ; 140(3): 263-272, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31474557

RESUMO

Atypical antipsychotics improve positive and negative symptoms but are not effective for treating cognitive impairments in patients with schizophrenia. We previously reported that cognitive impairments in neonatal ventral hippocampus (NVH)-lesioned rats show resistance to atypical antipsychotics risperidone and are associated with reduced calcium/calmodulin-dependent protein kinase II (CaMKII) and protein kinase C (PKC) signaling in memory-related regions. The cognitive enhancer ST101 (spiro[imi-dazo[1,2-a]pyridine-3,2-indan]-2(3H)-one) stimulates CaMKII activity in the hippocampus and medial prefrontal cortex (mPFC). We thus tested ST101 on cognitive impairments in NVH-lesioned rats. Chronic ST101 administration (0.1 and/or 0.5 mg/kg, p.o.) significantly improved deficits in prepulse inhibition (PPI), social interaction, and cognitive function in NVH-lesioned rats. ST101 administration (0.5 mg/kg, p.o.) significantly restored the decreased CaMKII autophosphorylation (Thr-286) in the mPFC and hippocampal CA1 regions of NVH-lesioned rats when assessed by immunohistochemistry. Chronic ST101 administration (0.1 mg/kg, p.o.) improved the decline in phosphorylation levels of CaMKII (Thr-286), PKCα (Ser-657), α-amino-3-hydroxy-5-methyl-4-isoxazol- propionic acid (AMPA)-type glutamate receptor subunit 1 (GluA1: Ser-831), and N-methyl-d-aspartate (NMDA) receptor subunit 1 (GluN1: Ser-896) in the mPFC and hippocampal CA1 regions. Taken together, these results suggest that ST101 improves schizophrenia-like behaviors and cognitive impairment by enhancing CaMKII/PKCα signaling in the mPFC and hippocampus in NVH-lesioned rats.


Assuntos
Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Transtornos Cognitivos/tratamento farmacológico , Hipocampo/efeitos dos fármacos , Indanos/farmacologia , Proteína Quinase C-alfa/metabolismo , Esquizofrenia/tratamento farmacológico , Transdução de Sinais/efeitos dos fármacos , Compostos de Espiro/farmacologia , Animais , Animais Recém-Nascidos , Antipsicóticos/farmacologia , Cognição/efeitos dos fármacos , Transtornos Cognitivos/metabolismo , Feminino , Hipocampo/metabolismo , Masculino , Memória/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/metabolismo , Risperidona/farmacologia , Esquizofrenia/metabolismo
16.
Horm Mol Biol Clin Investig ; 39(3)2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31483756

RESUMO

Background Modulatory effects of soy extract and estradiol on the central nervous system (CNS) have been reported. The effect of soy on scopolamine-induced spatial learning and memory in comparison to the effect of estradiol was investigated. Materials and methods Ovariectomized rats were divided into the following groups: (1) control, (2) scopolamine (Sco), (3) scopolamine-soy 20 (Sco-S 20), (4) scopolamine-soy 60 (Sco-S 60), (5) scopolamine-estradiol 20 (Sco-E 20) and (6) scopolamine-estradiol 60 (Sco-E 60). Soy extract, estradiol and vehicle were administered daily for 6 weeks before training in the Morris water maze (MWM) test. Scopolamine (2 mg/kg) was injected 30 min before training in the MWM test. Results In the MWM, the escape latency and traveled path to find the platform in the Sco group was prolonged compared to the control group (p < 0.001). Treatment by higher doses of soy improved performances of the rats in the MWM (p < 0.05 - p < 0.001). However, treatment with both doses of estradiol (20 and 60 µg/kg) resulted in a statistically significant improvement in the MWM (p < 0.01 - p < 0.001). Cortical, hippocampal and serum levels of malondialdehyde (MDA), as an index of lipid peroxidation, were increased which was prevented by soy extract and estradiol (p < 0.001). Cortical, hippocampal as well as serum levels of the total thiol, superoxide dismutase (SOD) and catalase (CAT) in Sco group were lower than the control group (p < 0.001) while they were enhanced when the animals were treated by soy extract and estradiol (p < 0.01 - p < 0.001). Conclusions It was observed that both soy extract and estradiol prevented learning and memory impairments induced by scopolamine in ovariectomized rats. These effects can be attributed to their protective effects on oxidative damage of the brain tissue.


Assuntos
Estradiol/farmacologia , Transtornos da Memória/etiologia , Memória/efeitos dos fármacos , Extratos Vegetais/farmacologia , Escopolamina/farmacologia , Soja/química , Aprendizagem Espacial/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Biomarcadores , Catalase/metabolismo , Feminino , Aprendizagem em Labirinto , Transtornos da Memória/tratamento farmacológico , Ovariectomia , Oxidantes/metabolismo , Estresse Oxidativo , Extratos Vegetais/química , Ratos , Superóxido Dismutase/metabolismo
17.
Biomed Pharmacother ; 118: 109349, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31545221

RESUMO

Neuroinflammation, a centralized immune response, is a physiological process by which the organism attempts to remove an injurious stimulus in the central nervous system. Nonetheless, it is known that chronic inflammatory processes play an important role in the onset and progression of neurodegenerative disorders, such as Alzheimer´s disease (AD). Based on this, new strategies to treat AD have been proposed. Among them, the use of non-steroidal anti-inflammatory drugs (NSAIDs) decreases the incidence of this disease. Unfortunately, the prolonged use of NSAIDs results in adverse secondary effects. In this context, plants secondary metabolites have become of great interest. Particularly, our group has demonstrated that the hydroalcoholic extract of Malva parviflora (MpHA) has anti-inflammatory effect and is capable of improving the cognitive deficit present in an AD model. To further characterize the Malva parviflora compounds with anti-inflammatory properties, here we generated a fraction from a dichloromethane extract, which constitutes a less complex mix of compounds than the MpHA. This approach allowed us to isolate a fraction (MpF10) with anti-inflammatory activity, able to ameliorate the spatial learning and memory impairment, and to reduce both astrogliosis as well as IL-1ß and TNF production in a murine model of LPS-mediated neuroinflammation. Among the identified compounds in the MpF10, we found daucosterol (MpDau), which prevented LPS-induced neuroinflammation. Interestingly, MpF10 and MpDau inhibit NFκB activity in macrophages exposed to LPS. Therefore, we propose that the compounds present in the MpF10 represent an alternative to treat neuroinflammation, an important process developed during neurodegenerative diseases such as AD.


Assuntos
Encéfalo/patologia , Inflamação/tratamento farmacológico , Malva/química , Extratos Vegetais/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Encéfalo/fisiopatologia , Inflamação/patologia , Lipopolissacarídeos , Macrófagos/efeitos dos fármacos , Macrófagos/patologia , Memória/efeitos dos fármacos , Camundongos , Extratos Vegetais/química , Extratos Vegetais/farmacologia
18.
Biomed Pharmacother ; 118: 109033, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31545235

RESUMO

Studies suggest that abnormal neurodevelopment of prefrontal striatal circuits is implicated in the pathogenesis of attention deficit hyperactivity disorder (ADHD). In the present study, we investigated the effect of catalpol, an active ingredient of Rehmanniae radix preparata, which is the most frequently used Chinese medicinal herb for the treatment of ADHD, on behavior and neurodevelopment in spontaneously hypertensive rats (SHR). SHR were divided into SHR group (vehicle, i.g.), methylphenidate (MPH) group (2 mg/kg/day, i.g.), and catalpol group (50 mg/kg/day i.g.), and Wistar-Kyoto (WKY) rats were used as control group (vehicle, i.g.). Open Field Test (OFT) and Morris water maze (MWM) test were performed to assess the effect of catalpol on behavior. Results revealed that both catalpol and MPH treatment decreased average speed, time spent in the central area, rearing times, and central area visits, increased the immobility time of SHR in OFT, and increased number of visits to the annulus, and time spent in target quadrant in the MWM test. Hematoxylin and eosin (H&E) staining showed that catalpol reduced irregular neuronal arrangement, ruptured nuclear membranes, and resulted in disappearance of the nucleolus in the prefrontal cortex (PFC) and striatum of SHR. Moreover, immuno-fluorescent staining of NeuN and myelin basic protein (MBP) indicated that catalpol ameliorated neuronal loss and contributed to myelination. Finally, western blot and immunostaining analysis suggested that several regulatory proteins involved in PFC development were up-regulated by catalpol treatment, such as brain-derived neurotrophic factor (BDNF), cyclin-dependent kinase 5 (Cdk5), p35, fibroblast growth factor (FGF) 21 and its receptor (FGFR)1. Taken together, catalpol can effectively ameliorate hyperactive and impulsive behavior, improve spatial learning and memory in SHR, likely through the neurodevelopmental pathways. Nonetheless, whether catalpol could attenuate inattention in SHR and the pathway by which catalpol reduces neuronal loss remain to be further studied.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Comportamento Animal/efeitos dos fármacos , Glucosídeos Iridoides/uso terapêutico , Atividade Motora/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Animais , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Estimulantes do Sistema Nervoso Central/uso terapêutico , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/patologia , Modelos Animais de Doenças , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Metilfenidato/uso terapêutico , Neurônios/efeitos dos fármacos , Neurônios/patologia , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/patologia , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY
19.
Int J Neurosci ; 129(12): 1203-1212, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31393204

RESUMO

Purpose of the study: Kaempferol (KM) is a flavonoid found in plant-derived foods and medicinal plants. Recently, it is well established that KM plays a protective role to develop Alzheimer's disease. The current study aimed at evaluating the effect of intracerebroventricular micro-injection of KM on memory retention of passive avoidance learning (MRPAM) and identifying the potentially related cholinergic mechanisms (ChMs) in rats. Materials and methods: In the current study, male Wistar rats randomly divided into control, vehicle and KM (10, 20 and 40 µg/rat) groups. Moreover, MRPAM was evaluated by shuttle box test. The role of ChM was studied using non-selective and selective acetylcholine antagonists (scopolamine [SCN], 4-DAMP and methoctramine [MN], respectively) as well as pirenzepine (PZ) in combination with KM. Results: The employment of KM (40 µg/rat) improved the SCN-induced memory impairment in MRPAM. Co-treatment with KM (40 µg/rat) plus 4-DAMP significantly increased the step-through latency (STL, P < 0.05; 167 ± 28 s) and decreased the total dark chamber (TDC, P < 0.05; 121 ± 31 s) compared with those of the 4-DAMP group (STL: 75 ± 13 s; TDC: 178 ± 46 s). Co-treatment with KM (40 µg/rat) plus PZ attenuated STL, and also increased TDC (P < 0.01; 220 ± 28 s) compared with those of the PZ group. Co-treatment with KM (10 and 20 µg/rat) and MN increased STL (P < 0.05), and deceased TDC compared with those of the MN group (P < 0.01). Conclusions: Totally, the results of the present study showed that cholinergic system may be involved in improving effect of KM on SCN-induced memory impairment.


Assuntos
Acetilcolina/fisiologia , Aprendizagem da Esquiva/efeitos dos fármacos , Antagonistas Colinérgicos/administração & dosagem , Quempferóis/administração & dosagem , Memória/efeitos dos fármacos , Antagonistas Muscarínicos/administração & dosagem , Animais , Aprendizagem da Esquiva/fisiologia , Diaminas/administração & dosagem , Injeções Intraventriculares , Masculino , Memória/fisiologia , Microinjeções , Piperidinas/administração & dosagem , Pirenzepina/administração & dosagem , Ratos Wistar , Escopolamina/administração & dosagem
20.
J Stroke Cerebrovasc Dis ; 28(11): 104288, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31395423

RESUMO

PURPOSE: The present study was to observe the therapeutic efficiency of Clematichinenoside (AR) on cerebral ischemic injury in rats, especially on neurological and motor function recovery and to explore the underlying mechanism. METHODS: Following middle cerebral artery occlusion/reperfusion (MCAO/R) surgery, rats were treated orally with 32, 16, and 8 mg/kg AR respectively for 14 days during which cerebral injury was evaluated and proinflammatory factors tumor necrosis factor-α and interleukin-6 as well as neurotrophic factors brain-derived neurotrophic factor and Neurotrophin-3 levels were determined with ELISA kits. Immunohistochemical analysis on number of neurons and reactive astrocytes in the hippocampus was to demonstrate the effect of AR on neuronal survival. Motor, learning, and memory recovery were assessed by Morris water maze, passive avoidance experiment, and rotatory rod test. Neuroprotection and anti-inflammation-related Notch and nuclear factor-κB (NF-κB) signaling pathways were analyzed by PCR and Western blot techniques on mammalian achaete-scute homologs1, Notch-1, intracellular Notch receptor domain, Jagged-1, transcription factor hairy, enhancer of split1 (Hes1), as well as the nuclear import of NF-κB in hippocampus. RESULTS: AR administration reduced cerebral injury in rats exposed to MCAO/R and after treatment of AR for 14 days, proinflammatory reaction was inhibited, with neuronal survival rate raised and motor function recovery facilitated. PCR and WB analysis of Notch/NF-κB signaling pathway revealed the inhibitory effect of AR on pathway related components. CONCLUSIONS: AR is beneficial to recovery of neurological and motor function in rats after cerebral ischemic injury via inhibiting Notch/NF-κB pathway.


Assuntos
Anti-Inflamatórios/farmacologia , Comportamento Animal/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Infarto da Artéria Cerebral Média/tratamento farmacológico , Atividade Motora/efeitos dos fármacos , NF-kappa B/metabolismo , Fármacos Neuroprotetores/farmacologia , Receptor Notch1/metabolismo , Saponinas/farmacologia , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Hipocampo/metabolismo , Hipocampo/patologia , Hipocampo/fisiopatologia , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/fisiopatologia , Infarto da Artéria Cerebral Média/psicologia , Masculino , Memória/efeitos dos fármacos , Neurotrofina 3/metabolismo , Ratos Sprague-Dawley , Recuperação de Função Fisiológica , Transdução de Sinais
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