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1.
J Agric Food Chem ; 68(3): 751-758, 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31861959

RESUMO

The present study aimed to investigate the combined effects of defatted walnut meal hydrolysate (DWMH) and tea polyphenols (TP) on learning improvement and to explain mechanistically why the combined treatments were more effective than either subject alone. In the step-down avoidance test and the Morris water maze test, codelivery of DWMH and TP was more effective than either individual supplement in reversing memory impairment in scopolamine-treated mice. Mixing with TP significantly facilitated the protective effects of DWMH or DWMH-derived peptides (cationic peptide P1 and anionic peptide P2) on H2O2-injured SH-SY5Y cells. Although combination treatment with TP and DWMH did not significantly alter systemic exposure to P1 or P2 in rats, it significantly increased the accumulation of the two peptides in the mouse brain. In addition, TP significantly improved cellular uptake of P1 and P2 by brain capillary endothelial cells, indicating that TP enhanced the blood-brain barrier permeation of DWMH-derived peptides. The proposed explanation for the advantage of combined treatment with TP and DWMH in reversing memory impairment was that TP enhanced both the protective effects of DWMH on nerve cells and the accumulation of DWMH in the brain. Our study can aid efforts to develop products and investigate the effects of nutrient combinations on brain disorders.


Assuntos
Camellia sinensis/química , Juglans/química , Transtornos da Memória/tratamento farmacológico , Fármacos Neuroprotetores/administração & dosagem , Extratos Vegetais/administração & dosagem , Polifenóis/administração & dosagem , Animais , Encéfalo/efeitos dos fármacos , Humanos , Aprendizagem/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/psicologia , Camundongos , Nozes/química , Ratos , Ratos Sprague-Dawley , Escopolamina/efeitos adversos
2.
Life Sci ; 238: 116898, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31610193

RESUMO

AIMS: Learning and memory impairment is a common symptom in the early stages of various types of dementia. It is likely to reduce the incidence of dementia with correct intervention. α-Asarone is the main bioactive substance isolated from Acorus tatarinowii Schott and has been proven to improve memory dysfunction; however, at present, the specific underlying mechanism is poorly understood. The aim of the present study was to investigate the effect of α-asarone on ethanol-impaired cognitive ability and explore the underlying mechanism in mice. MAIN METHODS: A mouse model of impaired learning and memory was created by ethanol (2.0 g/kg, i.g.). α-Asarone (7.5, 15 or 30 mg/kg, i.p.) was delivered 10 min prior to ethanol administration. The behavioral effect of α-asarone was evaluated using the novel object recognition test. Glutamate (Glu) and γ-aminobutyric acid (GABA) levels in the hippocampus were determined by ELISA, and the protein expression levels of hippocampal GluR2, NMDAR2B, SYNΙ, GLT-1 and CaMKⅡ were detected by western blotting. KEY FINDINGS: Pretreatment with α-asarone significantly improved the behavioral performance, regulated the imbalance of Glu and GABA in the hippocampus and the abnormal expression of related proteins. A possible underlying mechanism is regulation of the calcium signaling cascade to correct functioning of related proteins, and thus, maintain the level of Glu. SIGNIFICANCE: Our results show that the improvement in learning and memory elicited by α-asarone may providing a possible novel candidate for the prevention of learning and memory impairment in the early stages of dementia.


Assuntos
Anisóis/farmacologia , Depressores do Sistema Nervoso Central/toxicidade , Etanol/toxicidade , Fibrinolíticos/farmacologia , Hipocampo/efeitos dos fármacos , Aprendizagem/efeitos dos fármacos , Transtornos da Memória/tratamento farmacológico , Animais , Modelos Animais de Doenças , Ácido Glutâmico/metabolismo , Hipocampo/metabolismo , Masculino , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/metabolismo , Transtornos da Memória/patologia , Camundongos , Camundongos Endogâmicos C57BL , Neurotransmissores/metabolismo
3.
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
4.
Ecotoxicol Environ Saf ; 185: 109686, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31546205

RESUMO

Gestational exposure to PM2.5 is a worldwide environmental issue associated with long-lasting behavior abnormalities and neurodevelopmental impairments in the hippocampus of offspring. PM2.5 may induce hippocampus injury and lead to autism-like behavior such as social communication deficits and stereotyped repetitive behavior in children through neuroinflammation and neurodegeneration. Here, we investigated the preventive effect of B-vitamin on PM2.5-induced deleterious effects by focusing on anti-inflammation, antioxidant, synaptic remodeling and neurodevelopment. Pregnant mice were randomly divided into three groups including control group (mice subject to PBS only), model group (mice subject to both 30 µL PM2.5 of 3.456 µg/µL and 10 mL/(kg·d) PBS), and intervention group (mice subject to both 30 µL PM2.5 of 3.456 µg/µL and 10 mL/(kg·d) B-vitamin supplementation (folic acid, vitamin B6 and vitamin B12 with concentrations at 0.06, 1.14 and 0.02 mg/mL, respectively)). In the current study B-vitamin significantly alleviated neurobehavioral impairment reflected in reduced social communication disorders, stereotyped repetitive behavior, along with learning and spatial memory impairment in PM2.5-stimulated mice offspring. Next, B-vitamin corrected synaptic loss and reduced mitochondrial damage in hippocampus of mice offspring, demonstrated by normalized synapse quantity, synaptic cleft, postsynaptic density (PSD) thickness and length of synaptic active area. Furthermore, significantly down-regulated expression of pro-inflammatory cytokines including NF-κB, TNF-α and IL-1ß, and lipid peroxidation were found. We observed elevated levels of oxidant-related genes (SOD, GSH and GSH-Px). Moreover, decreased cleaved caspase-3 and TUNEL-positive cells suggested inhibited PM2.5-induced apoptosis by B-vitamin. Furthermore, B-vitamin increased neurogenesis by increasing EdU-positive cells in the subgranular zone (SGZ) of offspring. Collectively, our results suggest that B-vitamin supplementation exerts preventive effect on autism-like behavior and neurodevelopmental impairment in hippocampus of mice offspring gestationally exposed to PM2.5, to which alleviated mitochondrial damage, increased anti-inflammatory and antioxidant capacity and synaptic efficiency, reduced neuronal apoptosis and improved hippocampal neurogenesis may contribute.


Assuntos
Poluentes Atmosféricos/toxicidade , Transtorno Autístico/prevenção & controle , Hipocampo/efeitos dos fármacos , Material Particulado/toxicidade , Efeitos Tardios da Exposição Pré-Natal/prevenção & controle , Complexo Vitamínico B/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Transtorno Autístico/induzido quimicamente , Citocinas/metabolismo , Suplementos Nutricionais , Feminino , Hipocampo/crescimento & desenvolvimento , Hipocampo/imunologia , Aprendizagem/efeitos dos fármacos , Masculino , Camundongos Endogâmicos ICR , Neurogênese/efeitos dos fármacos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Sinapses/efeitos dos fármacos , Complexo Vitamínico B/administração & dosagem
5.
Environ Sci Pollut Res Int ; 26(28): 29257-29266, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31396869

RESUMO

An unsafe level of manganese (Mn) was detected in the drinking water in some arsenic (As)-contaminated areas in Bangladesh. Mn is an essential trace element; however, the intake of a higher level of Mn through the drinking water is associated with the development of toxicity in humans. This study was designed to evaluate the effects of As and Mn co-exposure on neurobehavioral and biochemical alterations in a mouse model. Sodium arsenite (10 mg/kg body weight) and manganese chloride tetrahydrate (10 mg/kg body weight) were given to mice individually and in combination with drinking water for 90 days. Results showed that individual As and Mn exposure as well as co-exposure of As and Mn significantly (p < 0.05) reduced the percent of time spent in the open arms when compared with that of control mice. In addition, percent of time spent in open arms significantly (p < 0.05) increased in co-exposed mice compared with As exposure in elevated plus maze (42.05 ± 1.10 versus 38.94 ± 0.66). In the Morris water maze test, the mean time latency to find the platform was longer in metal-treated mice in comparison to that of control mice (p < 0.05). Importantly, the co-exposed group had shorter time when compared with the As-exposed group during the training periods (p < 0.05). Moreover, co-exposed mice stayed significantly (p < 0.05) more time in the target quadrant in the probe trial in comparison with that of As-exposed mice (27.25 ± 1.21 versus 23.83 ± 0.87 s) but less time than control mice (27.25 ± 1.21 versus 43.17 ± 1.49 s). In addition, a significant (p < 0.05) alteration of biochemical parameters such as ALT, AST, ALP, BChE, and SOD as well as urea and creatinine levels were noted in the As-exposed group compared with the control group and Mn significantly (p < 0.05) attenuated the effects of As in co-exposed mice. Therefore, the results of this study suggest that As and Mn may have some antagonistic effect and Mn could attenuate the As-induced neurobehavioral and biochemical alterations in co-exposed mice.


Assuntos
Arsênico/toxicidade , Comportamento Animal/efeitos dos fármacos , Manganês/toxicidade , Animais , Arsenitos/toxicidade , Cloretos/toxicidade , Enzimas/sangue , Aprendizagem/efeitos dos fármacos , Masculino , Compostos de Manganês , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Compostos de Sódio/toxicidade , Memória Espacial/efeitos dos fármacos , Testes de Toxicidade/métodos , Poluentes Químicos da Água/toxicidade
6.
Neurochem Res ; 44(9): 2139-2146, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31376054

RESUMO

Morphine can influence immediate early genes (IEG) of activity-regulated cytoskeletal-associated protein (Arc) and brain-derived neurotrophic factor (BDNF) which are activated in response to physiological stimuli during learning, as well as the nerve growth factor (NGF) gene which increases the expression of several IEGs for memory formation. The purpose of the current study was first to evaluate the effect of acute (1-day) and subchronic (15-days) morphine administration on memory retrieval of rats and second to determine the hippocampal expression of NGF, BDNF and Arc genes as potential contributors in the observed effects in each setting. The effects of morphine (intraperitoneal, 10, 15 and 20 mg/kg) on memory function and gene expression were assessed using inhibitory avoidance test and real-time polymerase chain reaction, respectively. We found that a single dose of morphine at the highest dose of 20 mg/kg decreases the post-training step-through-latency, while repeated administration of the same dose for 15 successive days increases this indicator of memory retrieval. We did not detect a significant change in the hippocampal expression of Arc, BDNF or NGF genes after a single episode of morphine treatment. However, subchronic morphine administration (15 and 20 mg/kg) increased the expression of Arc and BDNF genes in a dose dependent manner. A higher mRNA expression for the NGF was observed at the higher dose of 20 mg/kg. We hypothesize that the subchronic effects were morphine-induced behavioral sensitization which may have been enhanced through increased hippocampal Arc expression.


Assuntos
Expressão Gênica/efeitos dos fármacos , Hipocampo/metabolismo , Aprendizagem/efeitos dos fármacos , Memória/efeitos dos fármacos , Morfina/farmacologia , RNA Mensageiro/metabolismo , Animais , Fator Neurotrófico Derivado do Encéfalo/genética , Proteínas do Citoesqueleto/genética , Genes Precoces/efeitos dos fármacos , Masculino , Fator de Crescimento Neural/genética , Proteínas do Tecido Nervoso/genética , Ratos Wistar
7.
J Ethnopharmacol ; 245: 112183, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31445134

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Hydrocotyle umbellata var.bonariensis Lam. (Hb), popularly known in Brazil as acariçoba and outside Brazil Hb by a number of names including marsh-pennywort, and many-flower, has traditionally been used in Ayurvedic medicine in the retardation of aging (Rasayana effect). AIM OF THE STUDY: The present study evaluated the effect of Hb treatment before and during paradoxical sleep deprivation (PSD) and sleep restriction (SR) on learning, memory, and acetylcholinesterase (AChE) brain activity. MATERIAL AND METHODS: Adult Swiss nulliparous female mice were randomly distributed among the experimental groups. The treated groups received the aqueous solution of Hb leaves orally at concentrations of 500 and 1.000 mg/kg. PSD and SR were induced by the multiple platform method, in which the animals remained for 3-days in PSD or 15-days in SR for 22 h per day. The collection of the vaginal epithelium occurred daily to determine the estrous cycle. Body mass gain was determined. The animals were submitted to the passive avoidance test and were then euthanized for the collection of brain tissue and the determination of cerebral cholinesterase activity. RESULTS: The aqueous solution of Hb was associated with a significant reduction in cholinesterase activity at both doses in the SR model, and at the dose of 1.000 mg/kg in the PSD model. Regarding the learning and memory test, the PSD group treated with 1.000 mg/kg presented significant improvement, whereas in the SR experiment none of the treated-groups showed any improvement in learning and memory. In the analysis of SR/PSD interference and/or Hb treatment on the estrous cycle, it was possible to observe that the treatment acted as a protector in the SR group, maintaining a normal cycle. CONCLUSIONS: The analyses showed that Hb was safe to use during periods of SR or PSD, acting as an adaptogen for these situations, in addition to being able to reduce cholinesterase activity, which suggests its neuroprotective action. In relation to the estrous cycle, Hb can act as a protector in SR situations.


Assuntos
Araliaceae , Aprendizagem/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Extratos Vegetais/uso terapêutico , Privação do Sono/tratamento farmacológico , Acetilcolinesterase/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Ciclo Estral/efeitos dos fármacos , Feminino , Camundongos , Fármacos Neuroprotetores/farmacologia , Extratos Vegetais/farmacologia , Folhas de Planta , Privação do Sono/metabolismo , Privação do Sono/fisiopatologia
8.
Neurochem Res ; 44(9): 2170-2181, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31420834

RESUMO

Acute inhalation of combustion smoke produces long-term neurologic deficits in survivors. To study the mechanisms that contribute to the development of neurologic deficits and identify targets for prevention, we developed a mouse model of acute inhalation of combustion smoke, which supports longitudinal investigation of mechanisms that underlie the smoke induced inimical sequelae in the brain. Using a transgenic mouse engineered to overexpress neuroglobin, a neuroprotective oxygen-binding globin protein, we previously demonstrated that elevated neuroglobin preserves mitochondrial respiration and attenuates formation of oxidative DNA damage in the mouse brain after smoke exposure. In the current study, we show that elevated neuronal neuroglobin attenuates the persistent inflammatory changes induced by smoke exposure in the mouse brain and mitigates concordant smoke-induced long-term neurobehavioral deficits. Specifically, we found that increases in hippocampal density of GFAP and Iba-1 positive cells that are detected post-smoke in wild-type mice are absent in the neuroglobin overexpressing transgenic (Ngb-tg) mice. Similarly, the smoke induced hippocampal myelin depletion is not observed in the Ngb-tg mice. Importantly, elevated neuroglobin alleviates behavioral and memory deficits that develop after acute smoke inhalation in the wild-type mice. Taken together, our findings suggest that the protective effects exerted by neuroglobin in the brains of smoke exposed mice afford protection from long-term neurologic sequelae of acute inhalation of combustion smoke. Our transgenic mouse provides a tool for assessing the potential of elevated neuroglobin as possible strategy for management of smoke inhalation injury.


Assuntos
Hipocampo/metabolismo , Inflamação/metabolismo , Neuroglobina/metabolismo , Animais , Doenças Desmielinizantes/induzido quimicamente , Doenças Desmielinizantes/metabolismo , Expressão Gênica/efeitos dos fármacos , Hipocampo/patologia , Inflamação/induzido quimicamente , Aprendizagem/efeitos dos fármacos , Locomoção/efeitos dos fármacos , Masculino , Memória/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Neurogênese/efeitos dos fármacos , Neuroglobina/genética , RNA Mensageiro/metabolismo , Fumaça
9.
Pharmacol Biochem Behav ; 185: 172764, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31449820

RESUMO

Zebra finches are songbirds that learn vocal patterns during a sensitive period of development that approximates adolescence. Exposure of these animals to a cannabinoid agonist during their period of sensorimotor vocal learning alters song patterns produced in adulthood. Thus, songbirds have unique value in studying developmental effects of drug exposure on a naturally learned behavior. A missing feature of this animal model has been a method to study drug reinforcement of behavior. To address this gap we have adapted place conditioning methods, used previously to determine that singing behavior is rewarding, to study cocaine reinforcement of behavior. We have found that cocaine dose-dependently reinforces both place conditioning and aversion at potencies consistent with those observed in mammalian species. Use of this place conditioning method has allowed us to determine that, when administered during periods of sensorimotor vocal learning, delta-9-THC, but not nicotine persistently increases sensitivity to cocaine through adulthood. Establishment of this method significantly expands the songbird drug exposure model, and holds promise for better appreciation of mechanisms important to sensorimotor learning that is dependent upon successful progress through sensitive periods of CNS development.


Assuntos
Cocaína/farmacologia , Dronabinol/farmacologia , Tentilhões/crescimento & desenvolvimento , Aprendizagem/efeitos dos fármacos , Vocalização Animal/efeitos dos fármacos , Análise de Variância , Animais , Comportamento Animal/efeitos dos fármacos , Cocaína/administração & dosagem , Condicionamento Clássico/efeitos dos fármacos , Relação Dose-Resposta a Droga , Dronabinol/administração & dosagem , Feminino , Masculino , Nicotina/administração & dosagem , Nicotina/farmacologia , Recompensa , Córtex Sensório-Motor/efeitos dos fármacos , Fatores Sexuais
10.
Biol Pharm Bull ; 42(7): 1146-1154, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31257291

RESUMO

Helicid (4-formylphenyl-O-ß-D-allopyranoside), an active component found in seeds from the Chinese herb Helicia nilagirica, has been reported to exert sedative, analgesic, hypnotic and antidepressant effects. The present study was designed to evaluate the antidepressant, learning and cognitive improvement effects of helicid in a chronic unpredictable mild stress (CUMS) model of depression in rats and to explore cAMP/protein kinase A (PKA)/cAMP response element-binding (CREB) signaling pathway. Sprague-Dawley rats were randomly assigned to six groups (n = 10): control; CUMS; CUMS + fluoxetine (5 mg/kg) and CUMS + helicid at 8, 16 and 32 mg/kg. All rats were subjected to 12 weeks of CUMS protocols and drug administration during the last 6 weeks of CUMS. Our results showed that helicid, at a dose of 32 mg/kg, significantly reversed decreases in body weight and sucrose consumption, increased the distance and number of crossings in the open-field test (OFT), reduced immobility times in the forced swimming test (FST) and improved spatial memory in the Morris water maze (MWM); all of these effects had been induced by CUMS paradigm. Immunohistochemistry showed that administration of helicid could promoted the proliferation of neurons in the hippocampal CA1 and dentate gyrus (DG) regions. CUMS rats treated with helicid had dramatically decreased protein levels of serotonin transporters (SERTs). In addition, CUMS resulted in a significant reduction in the expression of cAMP, PKA C-α and p-CREB, each of which were partially attenuated by helicid administration. These results indicated that helicid could improve depressive behaviors, learning and cognitive deficits and increase hippocampal neurogenesis, which may be mediated by the regulation of SERTs, activation of the cAMP/PKA/CREB signaling pathway and upregulation of p-CREB levels in hippocampal.


Assuntos
Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Benzaldeídos/farmacologia , Benzaldeídos/uso terapêutico , Depressão/tratamento farmacológico , Estresse Psicológico/tratamento farmacológico , Animais , Cognição/efeitos dos fármacos , AMP Cíclico/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Depressão/metabolismo , Depressão/psicologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/fisiologia , Aprendizagem/efeitos dos fármacos , Masculino , Neurogênese/efeitos dos fármacos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Estresse Psicológico/metabolismo , Estresse Psicológico/psicologia
11.
Cell Mol Neurobiol ; 39(8): 1151-1163, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31270712

RESUMO

Ischemic stroke often causes motor and cognitive deficits. Deregulated glia gap junction communication, which is reflected by increased protein levels of glial fibrillary acidic protein (GFAP) and connexin 43 (Cx43), has been observed in ischemic hippocampus and has been associated with cognitive impairment in animal stroke models. Here, we tested the hypothesis that reactive astrocytes-mediated loss of synaptophysin (SYP) and CREB-regulated transcription coactivator 1 (CRTC1) contribute to dysfunction in glia gap junction communication and memory impairment after ischemic stroke. Male Sprague-Dawley rats were subjected to a 90-min middle cerebral artery occlusion (MCAO) with 7-day reperfusion. Fluorocitrate (1 nmol), the reversible inhibitor of the astrocytic tricarboxylic acid cycle, was injected into the right lateral ventricle of MCAO rats once every 2 days starting immediately before reperfusion. The Morris water maze was used to assess memory in conjunction with western blotting and immunostaining to detect protein expression and distribution in the hippocampus. Our results showed that ischemic stroke caused significant memory impairment accompanied by increased protein levels of GFAP and Cx43 in hippocampal tissue. In addition, the levels of several key memory-related important proteins including SYP, CRTC1, myelin basic protein and high-mobility group-box-1 were significantly reduced in the hippocampal tissue. Of note, inhibition of reactive astrocytes with fluorocitrate was shown to significantly reverse the above noted changes induced by ischemic stroke. Taken together, our findings demonstrate that inhibiting reactive astrocytes with fluorocitrate immediately before reperfusion may protect against ischemic stroke-induced memory impairment through the upregulation of CRTC1 and SYP.


Assuntos
Astrócitos/metabolismo , Citratos/farmacologia , Aprendizagem/efeitos dos fármacos , Transtornos da Memória/fisiopatologia , Acidente Vascular Cerebral/metabolismo , Sinaptofisina/metabolismo , Fatores de Transcrição/genética , Regulação para Cima/efeitos dos fármacos , Animais , Astrócitos/efeitos dos fármacos , Isquemia Encefálica/patologia , Isquemia Encefálica/fisiopatologia , Conexina 43/metabolismo , Proteína Glial Fibrilar Ácida/metabolismo , Proteína HMGB1/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Masculino , Atividade Motora/efeitos dos fármacos , Proteína Básica da Mielina/metabolismo , Ratos Sprague-Dawley , Acidente Vascular Cerebral/fisiopatologia , Fatores de Transcrição/metabolismo
12.
Environ Sci Pollut Res Int ; 26(26): 27148-27167, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31321719

RESUMO

Extensive use of aluminum (Al) in industry, cooking utensils, and wrapping or freezing the food items, due to its cheapness and abundance in the environment, has become a major concern. Growing evidence supports that environmental pollutant Al promotes the aggregation of amyloid beta (Aß) in the brain, which is the main pathological marker of Alzheimer's disease (AD). Further, AD- and Al-induced neurotoxic effects are more common among women following reproductive senescence due to decline in estrogen. Though clinically Ginkgo biloba extract (GBE) has been exploited as a memory enhancer, its role in Al-induced neurotoxicity in reproductive senescent female rats needs to be evaluated. Animals were exposed to intraperitoneal dose (10 mg/kg b.wt) of Al and oral dose (100 mg/kg b.wt.) of GBE daily for 6 weeks. A significant decline in the Al-induced Aß aggregates was observed in hippocampal and cortical regions of the brain with GBE supplementation, as confirmed by thioflavin (ThT) and Congo red staining. GBE administration significantly decreased the reactive oxygen species, lipid peroxidation, nitric oxide, and citrulline levels in comparison to Al-treated rats. On the contrary, a significant increase in the reduced glutathione, GSH/GSSG ratio as well as in the activities of antioxidant enzymes was observed with GBE administration. Based on the above results, GBE prevented the neuronal loss in the hippocampus and cortex, hence caused significant improvement in the learning and memory of the animals in terms of AChE activity, serotonin levels, Morris water maze, and active and passive avoidance tests. In conclusion, GBE has alleviated the behavioral, biochemical, and histopathological alterations due to Al toxicity in rats. However, molecular studies are going on to better understand the mechanism of GBE protection against the environmental toxicant Al exposure. Graphical abstract .


Assuntos
Compostos de Alumínio/toxicidade , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Lactatos/toxicidade , Síndromes Neurotóxicas/tratamento farmacológico , Extratos Vegetais/farmacologia , Fatores Etários , Alumínio/toxicidade , Peptídeos beta-Amiloides/metabolismo , Animais , Antioxidantes/metabolismo , Encéfalo/metabolismo , Encéfalo/patologia , Enzimas/metabolismo , Feminino , Aprendizagem/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Memória/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Síndromes Neurotóxicas/etiologia , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Serotonina/metabolismo
13.
Folia Med (Plovdiv) ; 61(2): 258-265, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31301661

RESUMO

BACKGROUND: Parkinson's disease (PD) is the second most common neurode-generative disease, usually detected by its motor symptoms. The non-motor symptoms, including cognitive deficits, have been of great interest to researchers in the last few decades. AIM: To assess the effect of pramipexole on learning and memory in naïve and haloperidol-challenged rats. MATERIALS AND METHODS: Male Wistar rats divided into 9 groups (n=8): naïve - saline, pramipexole 0.5; 1 and 3 mg/kg bw; Haloperidol groups - saline, haloperidol, haloperidol + pramipexole 0.5; 1 and 3 mg/kg bw. Two-way active avoidance test (TWAA) and activity cage were performed. The studied parameters were: number of conditioned and unconditioned responses, vertical and horizontal movements. Statistical analysis was done using SPSS 19. RESULTS: The naïve experimental groups significantly increased the number of conditioned responses during the tests for short- and long-term memory, compared with the saline groups (p<0.05). During the short-memory test only the animals with the lowest dose of PMX significantly increased the number of unconditioned responses whereas during the long-term memory test all experimental groups increased the number of escapes in comparison with the saline groups (p<0.05). Challenge dose of haloperidol attenuates learning and memory in pramipexol treated rats. Only the highest dose of pramipexol showed significant increase in conditioned and unconditioned responses compared with the haloperidol group (p<0.05). CONCLUSION: Pramipexole improves learning and memory in naïve rats by enhancing dopaminergic neurotransmission. This is probably not the only mechanism involved. This is confirmed by the decrease in learning and memory ability in rats with haloperidol-challenge.


Assuntos
Aprendizagem da Esquiva/efeitos dos fármacos , Agonistas de Dopamina/farmacologia , Memória/efeitos dos fármacos , Pramipexol/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Antagonistas de Dopamina/farmacologia , Haloperidol/farmacologia , Aprendizagem/efeitos dos fármacos , Locomoção/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar
14.
Exp Brain Res ; 237(10): 2573-2584, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31352493

RESUMO

Patients with eating disorders exhibit problems with appetitive impulse control. Interactions between dopamine and serotonin (5-HT) neuron in this setting are poorly characterized. Here we examined 5-HT receptor-mediated changes in extracellular dopamine during impulsive appetitive behavior in rats. Rats were trained to perform a cued lever-press (LP) task for a food reward such that they stopped experiencing associated dopamine increases. Trained rats were administered the mixed 5-HT1B/2C-receptor antagonist metergoline, the 5-HT2A/2C-receptor antagonist ketanserin, and p-chlorophenylalanine (PCPA). We measured dopamine changes in the ventral striatum using voltammetry and examined the number of premature LPs, reaction time (RT), and reward acquisition rate (RAR). Compared with controls, metergoline increased premature LPs and shortened RT significantly; ketanserin decreased premature LPs and lengthened RT significantly; and PCPA decreased premature LPs, lengthened RT, and decreased RAR significantly. Following metergoline administration, rats exhibited a fast phasic dopamine increase for 0.25-0.75 s after a correct LP, but only during LP for an incorrect LP. No dopamine increases were detected with ketanserin or PCPA, or in controls. After LP task completion, metergoline also caused dopamine to increase slowly and remain elevated; in contrast, ketanserin caused dopamine to increase slowly and decrease rapidly. No slow dopamine increase occurred with PCPA. Inhibition of 5-HT1B- and 5-HT2C-receptors apparently induced dual modes of extracellular dopamine increase: fast phasic, and slow long-lasting. These increases may be associated with the suppression of acquired prediction learning and retention of high motivation for reward, leading to impulsive excessive premature LPs.


Assuntos
Comportamento Animal/efeitos dos fármacos , Dopamina/farmacologia , Receptor 5-HT2C de Serotonina/efeitos dos fármacos , Serotonina/farmacologia , Animais , Sinais (Psicologia) , Dopamina/metabolismo , Comportamento Impulsivo/efeitos dos fármacos , Ketanserina/farmacologia , Aprendizagem/efeitos dos fármacos , Ratos , Tempo de Reação , Receptores de Serotonina/efeitos dos fármacos , Receptores de Serotonina/fisiologia , Serotonina/metabolismo
15.
Pak J Pharm Sci ; 32(3 (Supplementary)): 1193-1199, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31303590

RESUMO

Cognitive behavior is associated with physiological processes that affect the working performance of an individual. Cognitive control is used to override self-serving impulses and behave in socially desirable manner. The objective of the study is to compare the effects of Choline with Fluoxetine and Clozapine for the modulation of cognitive behavior including learning, memory, locomotor, exploratory behavior and anxiety. The study was based on twenty four albino rats divided into four equal groups: (1) Control kept on normal saline (2) Fluoxetine (3) Clozapine (4) Choline. Morris Water Maze (WM) test was used for the psychological assessment based on neural mechanism involved in spatial learning and memory. Open field activity test evaluated locomotor and exploratory behavior. The behavior modulation in WM test and open field activity test was determined at 1st, 3rd, 5th and 7th week. Fluoxetine, Clozapine and Choline were used as drugs and administered to the rat groups mentioned earlier. The modulation of behavior in WM test and Open field activity test was recorded at 1st, 3rd, 5th and 7th week after administering the drugs. Impairment in learning behavior in Fluoxetine treated group was observed at 1st, 3rd, 5th and 7th week and in Clozapine group at 1st and 2nd week when compared to Control (Saline) group. Rise in latency time was observed in Fluoxetine treated group but was not significant. Clozapine and Choline had exhibited beneficial effects in memory retention and prevention of learning impairment. The findings have led to the conclusion that Choline and Clozapine improve the memory retention after continuous administration of 5 and 7 weeks. Moreover, Clozapine has different receptor specificity as compared to Choline. However, both improve the learning capability and enhance the memory in rats. Meanwhile, Fluoxetine did not show any considerable enhancement of memory.


Assuntos
Colina/farmacologia , Clozapina/farmacologia , Cognição/efeitos dos fármacos , Fluoxetina/farmacologia , Animais , Antipsicóticos/farmacologia , Comportamento Exploratório/efeitos dos fármacos , Aprendizagem/efeitos dos fármacos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Ratos
17.
Int J Neurosci ; 129(11): 1053-1065, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31215291

RESUMO

Aim: Alzheimer's disease (AD) is characterized by oxidative stress, neuroinflammation and progressive cognitive decline. Abscisic acid (ABA) is produced in a variety of mammalian tissues, including brain. It has anti-inflammatory and antioxidant effects and elicits a positive effect on spatial learning and memory performance. Here, the possible protective effect of ABA was evaluated in streptozotocin (STZ)-induced AD rat model which were injected intracerebroventriculary (i.c.v.) with STZ (3 mg/kg). Material and Methods: The STZ-treated animals received ABA (10 µg/rat, i.c.v.), ABA plus PPARß/δ receptor antagonist (GSK0660, 80 nM/rat) or ABA plus selective inhibitor of PKA (KT5720, 0.5 µg/rat) for 14 d. Learning and memory were determined using Morris water maze (MWM) and passive avoidance (PA) tests. Results: The data showed that STZ produced a significant learning and memory deficit in both MWM and PA tests. ABA significantly prevented the learning and memory impairment in STZ-treated rats. However, ABA effects were blocked by GSK0660 and KT5720. Conclusion: The data indicated that ABA attenuates STZ-induced learning and memory impairment and PPAR-ß/δ receptors and PKA signaling are involved, at least in part, in the ABA mechanism.


Assuntos
Ácido Abscísico/farmacologia , Doença de Alzheimer/tratamento farmacológico , Peptídeos e Proteínas de Sinalização Intracelular/farmacologia , Aprendizagem/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , PPAR delta/antagonistas & inibidores , PPAR beta/antagonistas & inibidores , Reguladores de Crescimento de Planta/farmacologia , Ácido Abscísico/administração & dosagem , Doença de Alzheimer/induzido quimicamente , Animais , Antibióticos Antineoplásicos/farmacologia , Aprendizagem da Esquiva/efeitos dos fármacos , Carbazóis/farmacologia , Modelos Animais de Doenças , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Fármacos Neuroprotetores/administração & dosagem , Pirróis/farmacologia , Ratos , Ratos Wistar , Estreptozocina/farmacologia , Sulfonas/farmacologia , Tiofenos/farmacologia
18.
Appl Microbiol Biotechnol ; 103(17): 7141-7149, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31236617

RESUMO

The newly reported associations between Alzheimer's disease (AD) and gut microbiota indicate the potential of gut microbiota regulation-based therapeutic intervention for AD. Silymarin and its main active component, silibinin, are promising natural agents against AD, while their acting mechanisms remain to be explored. The present study investigated the effects of silibinin and silymarin administration on behavioral and histological manifestations, and regulation on the gut microbiota of transgenic APP/PS1 mice. First, silibinin and silymarin administration could alleviate memory deficits and reduce the amyloid plaque burden in the brain of APP/PS1 mice in comparison with controls. Second, silibinin and silymarin administration tended to decrease the microbiota diversity and exhibited regulative effect in abundances on several key bacterial species associated with AD development. This implied that gut microbiota regulation by silibinin and silymarin might be involved in their effects against AD. Further studies are warranted to fully elucidate the molecular mechanisms.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Antioxidantes/uso terapêutico , Microbioma Gastrointestinal/efeitos dos fármacos , Silibina/uso terapêutico , Silimarina/uso terapêutico , Doença de Alzheimer/microbiologia , Doença de Alzheimer/patologia , Doença de Alzheimer/psicologia , Animais , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Biodiversidade , Modelos Animais de Doenças , Hipocampo/metabolismo , Aprendizagem/efeitos dos fármacos , Masculino , Camundongos , Camundongos Transgênicos , Placa Amiloide/metabolismo
19.
Artigo em Chinês | MEDLINE | ID: mdl-31189246

RESUMO

Objective: To Effects of n-hexane on learning and memory and the expressions of nerve growth factor (NGF) mRNA and nerve growth factor receptor (NGFR) mRNA of brain tissue in mice exposed to N-hexane. Methods: 40 Kunming mice were randomly divided into low-dose group, meddle-dose group, high-dose dose group and control group, with 10 mice in each group. All the groups were orally exposed to n-hexane in different doses: low-dose group with 43.5 mg/kg, middle-dose group with 86.5 mg/kg and high-dose group with 173.0 mg/kg, 1 time per day for 20 d. After the poisoning, the Y-arm test and the expressions of NGF mRNA and NGFR mRNA and the concentrations of NGF and NGFR in the brain tissues of each group were measured. Results: In the first Y-arm test, there existed a significant difference in correct reaction rate generally in all groups (P<0.05), and correct reaction rate in the middle-dose group and the high-dose group were low significantly compared with that in the control group(P<0.05). In the second Y-arm test, there existed a significant differences in total electric shock time and correct reaction rate generally in all groups (P<0.01), and the total electric shock time prolonged significantly and the correct response rate decreased significantly in 3 dose groups compared with those of the control group(P<0.05). The expression levels of NGF mRNA in brain tissues of low, meddle and high dose-groups were 0.81±0.66, 0.67±0.37 and 0.69±0.26, and the expression levels of NGFR mRNA were 1.22±0.42, 1.98±0.84 and 2.01±2.01, respectively. Compared with the control group, the expressions of NGF mRNA in the 3 dose groups decreased significantly (P<0.05), and the expression of NGFR mRNA in middle-and high-dose groups increased significantly (P<0.05). The concentrations of NGF in brain tissues of low,meddle and high dose-groups were 39.97±7.24 ng/L, 39.26±7.88 ng/L,31.70±8.21 ng/L,and the concentrations of NGFR were 17.37±6.82 ng/L,21.37±7.16 ng/L, 22.46±7.70 ng/L, respectively. Compared with the control group, the concentrations of NGF in high-dose groups decreased significantly(P<0.05), and the concentrations of NGFR in middle-and high-dose groups increased significantly (P<0.05). Conclusion: N-hexane exposure can result in decrease of learning and memory in mice, which may be related to abnormal expression of NGF mRNA and NGFR mRNA in brain tissue.


Assuntos
Hexanos , Aprendizagem , Memória , Fator de Crescimento Neural , Receptor de Fator de Crescimento Neural , Animais , Encéfalo , Hexanos/toxicidade , Aprendizagem/efeitos dos fármacos , Memória/efeitos dos fármacos , Camundongos , Fator de Crescimento Neural/efeitos dos fármacos , Fator de Crescimento Neural/metabolismo , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/metabolismo , Distribuição Aleatória , Receptores de Fator de Crescimento Neural
20.
Int J Dev Neurosci ; 76: 17-24, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31173822

RESUMO

As a general anesthesia drug, sevoflurane has been found to be potentially neurotoxic to the developing brain. Neuroglobin (Ngb) is a novel oxygen-carrying globulin that has been demonstrated to have neuroprotective effects in a variety of central nervous system disorders. However, it is unclear whether Ngb has a protective effect on nerve damage caused by sevoflurane. Therefore, this study was designed to investigate the effect and related mechanisms of Ngb on neural injury induced by sevoflurane. Pregnant rats on gestational day 20 (G20) were exposed to 3.5% sevoflurane for two hours, which led to an increase of Ngb on the 0-1st day after birth and decreased significantly on the 3rd day, while Cytochrome c increased from the 1 st day until the 7th day of offspring rats. Meanwhile, sevoflurane reduced Bcl-2 and Hif-1αand increased Bax and cleaved-caspase 3 in the third day after birth. Hemin inhibits endogenous apoptosis by increasing Ngb and Hif-1α. And increased Ngb improved the damage of long-term learning and memory induced by sevoflurane and increased the number of neurons in the hippocampus. We concluded that Ngb can improve the neuronal injury induced by sevoflurane exposure by inhibiting apoptosis and increasing the number of neurons. And this protective effect of Ngb may be related to Hif-1α signaling pathway. This finding may provide a novel therapeutic approach for sevoflurane -induced nerve damage.


Assuntos
Anestésicos Inalatórios/toxicidade , Apoptose/efeitos dos fármacos , Neuroglobina/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/patologia , Fármacos Neuroprotetores/farmacologia , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/prevenção & controle , Sevoflurano/toxicidade , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/crescimento & desenvolvimento , Encéfalo/patologia , Química Encefálica/efeitos dos fármacos , Citocromos c/metabolismo , Feminino , Hemina/farmacologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/efeitos dos fármacos , Aprendizagem/efeitos dos fármacos , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/prevenção & controle , Neuroglobina/biossíntese , Gravidez , Ratos , Transdução de Sinais/efeitos dos fármacos
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