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1.
J Ethnopharmacol ; 300: 115671, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36055476

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Kalyanaka ghrita (KG) is an Ayurvedic formulation traditionally used in the treatment of Daurbalya (debility) and Smritidaurbalya (impairment of intellectual activities). Clinical studies have reported the effect of KG in the treatment of Manasmandata or Buddhimandyata which is associated with impaired learning, social adjustment and maturation. AIM OF THE STUDY: The present study aims to standardization of KG and validation of its use in experimental models of neurodegeneration. MATERIALS AND METHODS: KG was Standardized for biomarkers curcumin, gallic acid, tannic acid, chebulagic acid, and berberine. In male wistar rats, neurodegeneration was induced by administration of intracerebroventricular Amyloid ß (Aß1-42). The effect of KG (oral and intranasal treatment) was evaluated through behavioral parameters such as Morris water maze, social recognition test, novel object recognition, locomotor activity, and molecular parameters, brain acetylcholinesterase, brain-derived neurotrophic factor (BDNF), inflammatory cytokines, oxidative stress markers, and antioxidants. Brain histopathology was performed for studying the architecture of the brain and plaque formation. RESULTS AND DISCUSSION: A novel HPLC method has been developed for the standardization of KG. Treatment with KG significantly improved cognition and memory and increased brain BDNF and antioxidant status in Aß1-42 induced rats. It also reduced brain acetylcholinesterase, oxidative stress, and inflammatory cytokines and prevented neuronal damage. There were more marked effects with intra-nasal administration compared to oral treatment. CONCLUSION: The findings suggest that KG has neuroprotective potential and along with its nootropic property could be a promising therapy for neurodegenerative diseases like Alzheimer's disease.


Assuntos
Doença de Alzheimer , Berberina , Curcumina , Fármacos Neuroprotetores , Nootrópicos , Acetilcolinesterase , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/toxicidade , Animais , Antioxidantes , Berberina/farmacologia , Fator Neurotrófico Derivado do Encéfalo , Curcumina/farmacologia , Citocinas/farmacologia , Modelos Animais de Doenças , Masculino , Aprendizagem em Labirinto , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , Nootrópicos/farmacologia , Ratos , Ratos Wistar , Taninos/farmacologia
2.
Int J Mol Sci ; 23(21)2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36362316

RESUMO

Vascular dementia (VaD) is a serious global health issue and type 2 diabetes mellitus (T2DM) patients are at higher risk. Palm oil tocotrienol-rich fraction (TRF) exhibits neuroprotective properties; however, its effect on VaD is not reported. Hence, we evaluated TRF effectiveness in T2DM-induced VaD rats. Rats were given a single dose of streptozotocin (STZ) and nicotinamide (NA) to develop T2DM. Seven days later, diabetic rats were given TRF doses of 30, 60, and 120 mg/kg orally for 21 days. The Morris water maze (MWM) test was performed for memory assessment. Biochemical parameters such as blood glucose, plasma homocysteine (HCY) level, acetylcholinesterase (AChE) activity, reduced glutathione (GSH), superoxide dismutase (SOD) level, and histopathological changes in brain hippocampus and immunohistochemistry for platelet-derived growth factor-C (PDGF-C) expression were evaluated. VaD rats had significantly reduced memory, higher plasma HCY, increased AChE activity, and decreased GSH and SOD levels. However, treatment with TRF significantly attenuated the biochemical parameters and prevented memory loss. Moreover, histopathological changes were attenuated and there was increased PDGF-C expression in the hippocampus of VaD rats treated with TRF, indicating neuroprotective action. In conclusion, this research paves the way for future studies and benefits in understanding the potential effects of TRF in VaD rats.


Assuntos
Demência Vascular , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Tocotrienóis , Ratos , Animais , Óleo de Palmeira , Tocotrienóis/farmacologia , Tocotrienóis/uso terapêutico , Demência Vascular/tratamento farmacológico , Demência Vascular/etiologia , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Acetilcolinesterase/metabolismo , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Superóxido Dismutase/metabolismo , Aprendizagem em Labirinto
3.
Molecules ; 27(21)2022 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-36363979

RESUMO

Scientific evidence suggests that quercetin (QUR) has anxiolytic-like effects in experimental animals. However, the mechanism of action responsible for its anxiolytic-like effects is yet to be discovered. The goal of this research is to assess QUR's anxiolytic effects in mouse models to explicate the possible mechanism of action. After acute intraperitoneal (i.p.) treatment with QUR at a dose of 50 mg/kg (i.p.), behavioral models of open-field, hole board, swing box, and light-dark tests were performed. QUR was combined with a GABAergic agonist (diazepam) and/or antagonist (flumazenil) group. Furthermore, in silico analysis was also conducted to observe the interaction of QUR and GABA (α5), GABA (ß1), and GABA (ß2) receptors. In the experimental animal model, QUR had an anxiolytic-like effect. QUR, when combined with diazepam (2 mg/kg, i.p.), drastically potentiated an anxiolytic effect of diazepam. QUR is a more highly competitive ligand for the benzodiazepine recognition site that can displace flumazenil (2.5 mg/kg, i.p.). In all the test models, QUR acted similar to diazepam, with enhanced effects of the standard anxiolytic drug, which were reversed by pre-treatment with flumazenil. QUR showed the best interaction with the GABA (α5) receptor compared to the GABA (ß1) and GABA (ß2) receptors. In conclusion, QUR may exert an anxiolytic-like effect on mice, probably through the GABA-receptor-interacting pathway.


Assuntos
Ansiolíticos , Camundongos , Animais , Ansiolíticos/farmacologia , Flumazenil/farmacologia , Quercetina/farmacologia , Moduladores GABAérgicos/farmacologia , Receptores de GABA/metabolismo , Receptores de GABA-A/metabolismo , Aprendizagem em Labirinto , Diazepam/farmacologia , Ácido gama-Aminobutírico/farmacologia , Ansiedade/tratamento farmacológico , Comportamento Animal
4.
PLoS One ; 17(11): e0277457, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36374861

RESUMO

BACKGROUND: Type-II diabetes mellitus (T2DM) is a major risk factor for cognitive impairment. Protecting the brain environment against inflammation, and neurodegeneration, as well as preservation of the BBB veracity through modulating the crosstalk between insulin/AKT/GSK-3ß and Wnt/ß-catenin signaling, might introduce novel therapeutic targets. PURPOSE: This study aimed at exploring the possible neuroprotective potential of vitamin D3 (VitD) and/or rosuvastatin (RSV) in T2DM-induced cognitive deficits. METHODS: T2DM was induced by a high-fat sucrose diet and a single streptozotocin (STZ) dose. Diabetic rats were allocated into a diabetic control and three groups treated with RSV (15 mg/kg/day, PO), VitD (500 IU/kg/day, PO), or their combination. RESULTS: Administration of VitD and/or RSV mitigated T2DM-induced metabolic abnormalities and restored the balance between the anti-inflammatory, IL 27 and the proinflammatory, IL 23 levels in the hippocampus. In addition, they markedly activated both the canonical and noncanonical Wnt/ß-catenin cassettes with stimulation of their downstream molecular targets. VitD and/or RSV upregulated insulin and α7 nicotinic acetylcholine (α7nACh) receptors gene expression, as well as blood-brain barrier integrity markers including Annexin A1, claudin 3, and VE-cadherin. Also, they obliterated hippocampal ApoE-4 content, Tau hyperphosphorylation, and Aß deposition. These biochemical changes were reflected as improved behavioral performance in Morris water maze and novel object recognition tests and restored hippocampal histological profile. CONCLUSION: The current findings have accentuated the neuroprotective potential of VitD and RSV and provide new incentives to expand their use in T2DM-induced cognitive and memory decline. This study also suggests a superior benefit of combining both treatments over either drug alone.


Assuntos
Disfunção Cognitiva , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Ratos , Animais , beta Catenina/metabolismo , Rosuvastatina Cálcica/uso terapêutico , Aprendizagem em Labirinto/fisiologia , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Vitamina D/farmacologia , Vitamina D/uso terapêutico , Vitamina D/metabolismo , Doenças Neuroinflamatórias , Glicogênio Sintase Quinase 3 beta/metabolismo , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/metabolismo , Via de Sinalização Wnt , Hipocampo/metabolismo , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Insulina/metabolismo
5.
PLoS One ; 17(11): e0277414, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36374865

RESUMO

The mammalian hippocampus (Hp) can be functionally segregated along its septotemporal axis, with involvement of dorsal hippocampus (dHp) in spatial memory and ventral hippocampus (vHp) in stress responses and emotional behaviour. In the present study, we investigate comparable functional segregation in proposed homologues within the avian brain. Using Japanese quail (Coturnix Japonica), we report that bilateral lesions of the rostral hippocampus (rHp) produce robust deficits in a spatial Y-maze discrimination (YMD) test while sparing performance during contextual fear conditioning (CFC), comparable to results from lesions to homologous regions in mammals. In contrast, caudal hippocampus (cHp) lesions failed to produce deficits in either CFC or YMD, suggesting that, unlike mammals, both cHp and rHp of birds can support emotional behavior. These observations demonstrate functional segregation along the rostrocaudal axis of the avian Hp that is comparable in part to distinctions seen along the mammalian hippocampal septotemporal axis.


Assuntos
Coturnix , Hipocampo , Animais , Coturnix/fisiologia , Hipocampo/fisiologia , Aprendizagem em Labirinto/fisiologia , Memória Espacial , Medo , Mamíferos
6.
Behav Neurosci ; 136(6): 561-574, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36395015

RESUMO

Successful navigation depends critically upon two broad categories of spatial navigation strategies that include allocentric and egocentric reference frames, relying on external or internal spatial information, respectively. As with older adults, aged rats show robust impairments on a number of different spatial navigation tasks. There is some evidence that these navigation impairments are accompanied by a bias toward relying on egocentric over allocentric navigation strategies. To test the degree to which young and aged animals utilize these two navigation approaches, a novel behavioral arena was used in which rats are trained to traverse a circular track and to stop at a learned goal location that is fixed with respect to a panorama of visual cues projected onto the surrounding walls. By instantaneously rotating the cues, allocentric and egocentric reference frames were put in direct and immediate conflict and goal navigation performance was assessed with respect to how accurately young and aged animals were able to utilize the rotated cues. Behavioral data collected from nine young and eight aged animals revealed that both age groups were able to update their navigation performance following cue rotation. Contrary to what was expected, however, aged animals showed more accurate overall goal navigation performance, stronger allocentric strategy use, and more evident changes in behavior in response to cue rotation compared to younger animals. The young rats appeared to mix egocentric and allocentric strategies for ICR task solution. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Assuntos
Comportamento Animal , Sinais (Psicologia) , Navegação Espacial , Animais , Ratos , Aprendizagem em Labirinto/fisiologia , Navegação Espacial/fisiologia
7.
Nutrients ; 14(21)2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36364879

RESUMO

Dietary fish intake has proven to have health benefits in humans. n-3 polyunsaturated fatty acids (PUFAs) in fish oil (FO), especially, may provide protection against age-related cognitive disorders. Owing to the unique benefits of n-3 PUFAs, other nutrients, such as fish protein (FP), have not been well studied. To clarify the effects of FO and FP on brain function, we investigated whether FO or FP feeding can prevent age-related cognitive dysfunction in senescence-accelerated mouse-prone 10 (SAMP10) mice. The FP group maintained a better working memory compared to the control and FO groups in the Y-maze test, but not episodic memory in the novel object recognition test. To evaluate demyelination levels, we measured neurofilament H (NfH) and myelin basic protein (MBP) immunoreactivity in the hippocampus (Hipp). Axon morphology was maintained in the FP group, but not in the control and FO groups. Additionally, the percentage of positive area for double-staining with NfH/MPB was significantly higher in the Hipp of FP-fed mice than in the control (p < 0.05). These results suggest that FP intake prevents age-related cognitive dysfunction by maintaining axonal morphology in the Hipp of SAMP10 mice.


Assuntos
Ácidos Graxos Ômega-3 , Memória de Curto Prazo , Humanos , Animais , Camundongos , Alaska , Óleos de Peixe/farmacologia , Aprendizagem em Labirinto
8.
Acta Neurobiol Exp (Wars) ; 82(3): 380-388, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36214720

RESUMO

Memory and cognitive impairment induced by oxidative stress are among the main hallmarks of Alzheimer's disease's (AD) pathology. The present study aimed to investigate the potential neuroprotective effects of Thymus daenensis (T. daenensis) extract against scopolamine­induced memory impairment and oxidative stress in rats. T. daenensis, widely distributed in Iran and Europe, is known to be a rich source of natural antioxidants and has been traditionally used for various medical purposes. The present study investigated the post­treatment effects of T. daenensis on learning and memory functions, antioxidant cellular defense, and oxidative stress using the scopolamine rat model of AD. The experiments were performed by intraperitoneal injection of scopolamine for 10 consecutive days in Wistar male rats (180-220 g). Additionally, the animals received T. daenensis extract (50­200 mg/kg) by gavage for 14 consecutive days after induction of memory impairment. The animals were divided into 8 groups, namely: control, 200 mg/kg of T. daenensis extract (D200), donepezil (DON), scopolamine (ALZ), ALZ animals treated with different doses of the extract (ALZ+D50 or 100 or 200 mg/kg) and ALZ animals treated with (ALZ+DON). The animals were then subjected to the Morris water maze (MWM) paradigm as a standard criterion for memory function assessment, and after extracting the brain tissues, the related biochemical oxidative stress parameters were determined in the brain. Our results indicated that T. daenensis extract significantly improved animals' performance in the MWM while significantly reducing oxidative stress and antioxidant imbalance. Furthermore, the extract did not show hepatotoxic effects on treated animals. In addition, the extract treatment significantly decreased both cellular malondialdehyde (MDA) and protein carbonyl (PCO) content while conversely increasing the total reduced glutathione (GSH) content and also the levels of total and endogenous antioxidants in the ferric reducing antioxidant power (FRAP) assay. It seems that the administration of T. daenensis significantly improved both cellular biochemical aspects and memory performance in animal models. Conclusively, it could be beneficial for scopolamine­induced neurotoxicity.


Assuntos
Fármacos Neuroprotetores , Escopolamina , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Donepezila/efeitos adversos , Glutationa/metabolismo , Masculino , Malondialdeído/metabolismo , Aprendizagem em Labirinto , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/prevenção & controle , Fármacos Neuroprotetores/uso terapêutico , Estresse Oxidativo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos , Ratos Wistar , Escopolamina/toxicidade
9.
Int J Mol Sci ; 23(19)2022 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-36232453

RESUMO

The presynaptic protein Mover/TPRGL/SVAP30 is absent in Drosophila and C. elegans and differentially expressed in synapses in the rodent brain, suggesting that it confers specific functions to subtypes of presynaptic terminals. In order to investigate how the absence of this protein affects behavior and learning, Mover knockout mice (KO) were subjected to a series of established learning tests. To determine possible behavioral and cognitive alterations, male and female 8-week-old KO and C57Bl/6J wildtype (WT) control mice were tested in a battery of memory and anxiety tests. Testing included the cross maze, novel object recognition test (NOR), the Morris water maze (MWM), the elevated plus maze (EPM), and the open field test (OF). Mover KO mice showed impaired recognition memory in the NOR test, and decreased anxiety behavior in the OF and the EPM. Mover KO did not lead to changes in working memory in the cross maze or spatial reference memory in the MWM. However, a detailed analysis of the swimming strategies demonstrated allocentric-specific memory deficits in male KO mice. Our data indicate that Mover appears to control synaptic properties associated with specific forms of memory formation and behavior, suggesting that it has a modulatory role in synaptic transmission.


Assuntos
Ansiedade , Caenorhabditis elegans , Animais , Comportamento Animal , Comportamento Exploratório , Feminino , Masculino , Aprendizagem em Labirinto , Transtornos da Memória , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Memória Espacial
10.
Nutrients ; 14(20)2022 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-36296969

RESUMO

Alzheimer's disease is a global public health problem and the most common form of dementia. Due to the failure of many single therapies targeting the two hallmarks, Aß and Tau, and the multifactorial etiology of AD, there is now more and more interest in nutraceutical agents with multiple effects such as Moringa oleifera (MO) that have strong anti-oxidative, anti-inflammatory, anticholinesterase, and neuroprotective virtues. In this study, we treated APP/PS1 mice with a methanolic extract of MO for four months and evaluated its effect on AD-related pathology in these mice using a multitude of behavioral, biochemical, and histochemical tests. Our data revealed that MO improved behavioral deficits such as anxiety-like behavior and hyperactivity and cognitive, learning, and memory impairments. MO treatment abrogated the Aß burden to wild-type control mice levels via decreasing BACE1 and AEP and upregulating IDE, NEP, and LRP1 protein levels. Moreover, MO improved synaptic plasticity by improving the decreased GluN2B phosphorylation, the synapse-related proteins PSD95 and synapsin1 levels, the quantity and quality of dendritic spines, and neurodegeneration in the treated mice. MO is a nutraceutical agent with promising therapeutic potential that can be used in the management of AD and other neurodegenerative diseases.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Moringa oleifera , Camundongos , Animais , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Secretases da Proteína Precursora do Amiloide/metabolismo , Ácido Aspártico Endopeptidases/metabolismo , Inibidores da Colinesterase/farmacologia , Camundongos Transgênicos , Aprendizagem em Labirinto , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Doença de Alzheimer/metabolismo , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/metabolismo , Plasticidade Neuronal
11.
Exp Gerontol ; 169: 111981, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36270545

RESUMO

The incidence of aging-related cognitive decline is increasing with population aging. It is urgent to explore ways to ameliorate aging-related cognitive decline. Cognitive-exercise dual-task intervention has shown beneficial effects on improving cognition in aging cohorts, but the mechanisms of the effects remain unclear. In this study, 18-month-old Sprague Dawley rats served as a model of natural aging. First, the performance in the Morris water maze test and the change in synaptophysin content in the hippocampus were used to investigate the cognitive decline of 18-month-old rats. Then, a batch of 18-month-old rats was treated with cognitive, exercise, or cognitive-exercise dual-task intervention for 12 weeks. The novel object recognition test was used to assess cognitive ability. Enzyme-linked immunosorbent assay and Western blotting were used to detect the levels of oxidative stress molecules and synaptic plasticity-related proteins. We found that cognitive-exercise dual-task intervention improved the discrimination index of natural aging rats. After dual-task intervention, the expression levels of synaptophysin, brain-derived neurotrophic factor, superoxide dismutase, and glutathione peroxidase were increased, and the expression level of lipid peroxide malondialdehyde was decreased. Furthermore, the effect of dual-task intervention on synaptic plasticity-related proteins and oxidative stress indicators was greater than that of single cognitive or exercise intervention. In conclusion, cognitive-exercise dual-task intervention can significantly ameliorate aging-related cognitive decline, and the improvement might be related to the reduction of oxidative stress and the enhancement of synaptic plasticity. The effect of cognitive-exercise dual-task intervention may be better than that of single cognitive or exercise intervention.


Assuntos
Disfunção Cognitiva , Plasticidade Neuronal , Ratos , Animais , Sinaptofisina/metabolismo , Aprendizagem em Labirinto , Ratos Sprague-Dawley , Envelhecimento/psicologia , Disfunção Cognitiva/prevenção & controle , Disfunção Cognitiva/metabolismo , Hipocampo/metabolismo , Estresse Oxidativo , Cognição
12.
Ecotoxicol Environ Saf ; 246: 114180, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36265406

RESUMO

Benzo[a]pyrene (B[a]P) is a widespread carcinogenic pollutant in the environment. Although previous studies have demonstrated the neurodevelopmental toxicity of B[a]P, the precise mechanisms underlying the neurotoxic effects induced by prenatal B[a]P exposure remain largely unknown. In the present study, pregnant Sprague-Dawley (SD) rats were injected intraperitoneally with 0, 10, 20, or 40 mg/kg-bw of B[a]P for three consecutive days on embryonic days 17-19. The learning and memory abilities of offspring were determined by Morris Water Maze (MWM) test, while the number of dendritic branches and the density of dendritic spines in hippocampal CA1 and DG regions were evaluated by Golgi-Cox staining at PND 45 and PND 75. The mRNA expression of BDNF, PSD-95, and SYP in offspring hippocampus were detected by qRT-PCR, and the protein expression of BDNF, PSD-95, SYP, HDAC2, acH3K9, and acH3K14 were measured by Western blotting or immunohistochemistry. CHIP-PCR was performed to further detect the levels of acH3K9 and acH3K14 in the promoter regions of BDNF and PSD-95 genes. Our results showed that rats prenatally exposed to B[a]P exhibited impaired spatial learning and memory abilities and the number of dendritic branches and the density of dendritic spines in the hippocampal CA1 and DG regions were significantly reduced during adolescence and adulthood. The expression of HDAC2 protein was significantly upregulated, while acH3K9, acH3K14, BDNF, PSD-95, and SYP protein levels were significantly downregulated in the hippocampus of B[a]P- exposed rats. In addition, CHIP results showed that prenatal B[a]P exposure markedly decreased the level of acH3K9 and acH3K14 in the promoter region of BDNF and PSD-95 gene in the hippocampus of PND 45 and PND 75 offspring. All of the results suggest that prenatal B[a]P exposure impairs cognitive function and hippocampal synaptic plasticity of offspring in adolescence and adulthood, and HDAC2-mediated histone deacetylation plays a crucial role in these deficits.


Assuntos
Benzo(a)pireno , Efeitos Tardios da Exposição Pré-Natal , Gravidez , Feminino , Humanos , Animais , Ratos , Ratos Sprague-Dawley , Benzo(a)pireno/toxicidade , Benzo(a)pireno/metabolismo , Histonas/genética , Histonas/metabolismo , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Hipocampo , Plasticidade Neuronal , Aprendizagem Espacial , Cognição , Aprendizagem em Labirinto , Histona Desacetilase 2/genética , Histona Desacetilase 2/metabolismo , Histona Desacetilase 2/farmacologia
13.
Exp Brain Res ; 240(12): 3259-3270, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36301335

RESUMO

Numerous studies have shown the deleterious effects of sleep deprivation (SD) on memory. However, SD in various durations may induce different effects. Studies have reported that short-term or acute SD can improve cognitive functions. In addition, streptozotocin (STZ) significantly impairs learning and memory, and induces inflammation and oxidative stress. In this study, we aimed to investigate the effect of two types of SD (short term: 6 h; long term: 24 h) on STZ-induced spatial memory impairment in rats, with respect to the serum level of catalase (CAT), malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1beta (IL-1ß). Morris water maze apparatus was used to assess spatial memory performance and STZ was injected i.c.v., twice, and at the dose of 3 mg/kg, at an interval of 48 h. The results showed that only 24 h SD impaired spatial learning and memory in rats. In addition, 24 h SD attenuated anti-oxidant activity and increased the level of pro-inflammatory markers in the serum. STZ impaired spatial learning and memory, and attenuated anti-oxidant activity and increased the level of pro-inflammatory markers in the serum of rats. Furthermore, 6 h SD slightly and partially improved spatial memory and significantly improved anti-oxidant activity in rats, with no effect on STZ-induced inflammation. We suggest that STZ has more important mechanisms that are involved in its memory impairment effect, and maybe, STZ-induced inflammation has a more important role. We also suggest more detailed studies to investigate the potential therapeutic effect of SD (in different durations) on memory function, oxidative stress, and inflammation.


Assuntos
Doença de Alzheimer , Animais , Ratos , Estreptozocina/toxicidade , Doença de Alzheimer/tratamento farmacológico , Aprendizagem em Labirinto , Antioxidantes/efeitos adversos , Privação do Sono/complicações , Hipocampo , Ratos Wistar , Transtornos da Memória/induzido quimicamente , Estresse Oxidativo , Biomarcadores , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico
14.
Neuroscience ; 505: 21-33, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36265757

RESUMO

Accumulating evidence suggests that neuroinflammation is the main mechanism in cognitive dysfunction and that brain-derived neurotrophic factor (BDNF) is involved in learning and memory by binding to tyrosine kinase B (TrkB) receptors. Herein, we tested the roles of the BDNF-TrkB signaling pathway and its downstream cascade in lipopolysaccharide (LPS) induced cognitive dysfunction in mice. Mice were treated with LPS (0.25 mg/kg) for 7 days, and learning and memory function was evaluated by the novel object recognition test (NORT). Western blotting was performed to elucidate roles of the BDNF-TrkB signaling pathway and its downstream cascades in LPS mice. The NORT showed that LPS induced learning and memory deficits in mice. The levels of IL-1ß, IL-6, and TNF-α in the serum and central nervous system decreased in LPS mice. In addition, LPS reduced the protein levels of BDNF, p-TrkB, Bcl-2, p-ERK1/2, p-CaMK2, p-CREB and p-GluR1 and increased the expression of Bax in the hippocampus and medial prefrontal cortex regions. In the entorhinal cortex, the protein levels of BDNF, p-TrkB, Bcl-2, p-CaMK2 and p-CREB were decreased, and the protein level of Bax was increased in LPS mice. Interestingly, 7,8-DHF alleviated these disorders in LPS mice and improved learning and memory function; however, the TrkB antagonist ANA12 effectively reversed effects of 7,8-DHF. Therefore, we conclude that the BDNF-TrkB signaling pathway and its downstream cascades disorders in different regions are main mechanisms of cognitive dysfunction, and 7,8-DHF maybe useful as a new treatment for preventing or treating cognitive dysfunction induced by neuroinflammation in neurodegenerative diseases.


Assuntos
Fator Neurotrófico Derivado do Encéfalo , Receptor trkB , Animais , Camundongos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Receptor trkB/metabolismo , Proteínas Tirosina Quinases/metabolismo , Lipopolissacarídeos/farmacologia , Doenças Neuroinflamatórias , Proteína X Associada a bcl-2/metabolismo , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/metabolismo , Transdução de Sinais , Hipocampo/metabolismo , Aprendizagem em Labirinto
15.
Food Funct ; 13(22): 11615-11626, 2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36268846

RESUMO

Alcohol-induced cognitive impairment (AICI) has become a public health concern and thus effective intervention is urgently needed. The present study aims to assess the amelioration effect of walnut protein hydrolysate (WPH) in AICI rats and elucidate the associated mechanism. The Morris water maze task verified the significant amelioration effect of WPH against learning and memory deficits. Moreover, a reduction of oxidative stress and inflammation in brain tissues was observed and the significant enhancement of brain-derived neurotrophic factor (BDNF), postsynaptic density protein (PSD95) and cAMP-response element binding protein (p-CREB) expression (P < 0.05) indicated the rescue of damaged hippocampal synaptic plasticity. In addition, after WPH administration, disorders of ERK and caspase-3 signal pathways, abnormality in the release of the neurotransmitters acetylcholine (ACh) and gamma-aminobutyric acid (GABA), and histopathological impairment in the hippocampus of AICI rats were ameliorated in a dose-dependent manner. Overall, the amelioration of AICI by WPH might result from the alleviation of oxidative stress and inflammation in brain tissue and the improvement of hippocampal synaptic plasticity.


Assuntos
Disfunção Cognitiva , Juglans , Animais , Ratos , Ratos Sprague-Dawley , Juglans/metabolismo , Hidrolisados de Proteína/metabolismo , Aprendizagem em Labirinto , Hipocampo/metabolismo , Plasticidade Neuronal , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Disfunção Cognitiva/metabolismo , Encéfalo/metabolismo , Estresse Oxidativo , Inflamação/metabolismo
16.
Metab Brain Dis ; 37(8): 2871-2881, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36181652

RESUMO

Although the association of prolonged use of proton pump inhibitors, such as omeprazole, with memory impairment has been reported more than two decades ago, its underlying molecular mechanism is yet to be determined. Thus, in this study, we aimed to determine the mechanisms underlying the effect of prolonged omeprazole treatment on hippocampal synaptic function and spatial memory in male rats. Adult rats were subcutaneously administered with omeprazole for 12 or 24 weeks. Spatial memory was assessed using the Morris water maze (MWM) test. We examined the hippocampal protein expression of synaptic plasticity proteins, including the AMPA receptor subunit GluA1, postsynaptic density-95 (PSD-95), and activity-regulated cytoskeleton-associated protein (Arc), and the hippocampal expression and localization of androgen receptor (AR). In the MWM test, the escape latency was found to be significantly higher, and the number of platform crossings and the time spent in the target quadrant were significantly lower in the rats treated with omeprazole compared to the control rats. Hypomagnesemia and lower bone and brain Mg2+ content were also detected in the omeprazole-treated groups compared with the control group. The expression of GluA1, PSD-95, and Arc in the hippocampus and the expression of AR in the dentate gyrus and CA1 of the hippocampus were significantly lower in the omeprazole-treated groups than in the control group. These results suggest that prolonged omeprazole treatment might lead to memory deficit by impairing glutamate receptor trafficking or synaptic anchoring. Hypomagnesemia and brain Mg2+ deficiency may be, at least in part, involved in omeprazole-induced memory impairment.


Assuntos
Omeprazol , Memória Espacial , Ratos , Masculino , Animais , Aprendizagem em Labirinto , Omeprazol/farmacologia , Omeprazol/metabolismo , Hipocampo/metabolismo , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/metabolismo
17.
Physiol Behav ; 257: 113969, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36181786

RESUMO

Prolonged daily intake of Western-type diet rich in saturated fats and sugars, and exposure to early life stress have been independently linked to impaired neurodevelopment and behaviour in animal models. However, sex-specific effects of both environmental factors combined on spatial learning and memory, behavioural flexibility, and brain oxidative capacity have still not been addressed. The current study aimed to evaluate the impact of maternal and postnatal exposure to a high-fat and high-sugar diet (HFS), and exposure to early life stress by maternal separation in adult male and female Wistar rats. For this purpose, spatial learning and memory and behavioural flexibility were evaluated in the Morris water maze, and regional brain oxidative capacity and oxidative stress levels were measured in the hippocampus and medial prefrontal cortex. Spatial memory, regional brain oxidative metabolism, and levels of oxidative stress differed between females and males, suggesting sexual dimorphism in the effects of a HFS diet and early life stress. Males fed the HFS diet performed better than all other experimental groups independently of early life stress exposure. However, behavioural flexibility evaluated in the spatial reversal leaning task was impaired in males fed the HFS diet. In addition, exposure to maternal separation or the HFS diet increased the metabolic capacity of the prefrontal cortex and dorsal hippocampus in males and females. Levels of oxidative stress measured in the latter brain regions were also increased in groups fed the HFS diet, but maternal separation seemed to dampen regional brain oxidative stress levels. Therefore, these results suggest a compensatory effect resulting from the interaction between prolonged exposure to a HFS diet and early life stress.


Assuntos
Experiências Adversas da Infância , Aprendizagem Espacial , Animais , Ratos , Feminino , Masculino , Ratos Wistar , Privação Materna , Aprendizagem em Labirinto , Caracteres Sexuais , Dieta Ocidental/efeitos adversos , Hipocampo/metabolismo , Encéfalo/metabolismo , Dieta Hiperlipídica
18.
ACS Chem Neurosci ; 13(21): 3057-3067, 2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36245095

RESUMO

Vascular dementia (VaD), one of the major consequences after stroke, is the second reason for the cognitive decline in aged people. Chronic cerebral hypoperfusion (CCH) is considered as the main cause for cognitive impairment in VaD patients. In our previous study, a synthetic compound, 4-trifluoromethyl-(E)-cinnamoyl]-L-4-F-phenylalanine acid (AE-18), has been proven to decrease infarct volume and to recover the insufficient blood supply after ischemia-reperfusion in rats, which was reminded that AE-18 may possess the ameliorative effect in CCH. In this study, the bilateral common carotid artery occlusion was performed to establish the CCH model in rats to evaluate the effect and mechanisms of AE-18 in CCH. Results showed that AE-18 (5 and 10 mg/kg, i.g.) could recover the learning and memory and increase the number of neurons in the hippocampus, which may be attributed to its neurogenesis effects and its recovery of cerebral blood flow in CCH rats. In addition, the in vitro studies showed that AE-18 promoted neuronal proliferation, induced differentiation of Neuro-2a cells into a neuron-like morphology, and accelerated the establishment of axon-dendrite polarization of primary hippocampal neurons through upregulating brain-derived neurotrophic factor via the PI3K/Akt/CREB pathway. In conclusion, AE-18 is a promising candidate for the treatment of cognitive decline after CCH injury by restoring blood supply to the brain and promoting neurogenesis in the hippocampus.


Assuntos
Isquemia Encefálica , Demência Vascular , Animais , Ratos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fenilalanina/metabolismo , Neurogênese , Isquemia Encefálica/metabolismo , Hipocampo/metabolismo , Aprendizagem em Labirinto , Modelos Animais de Doenças
19.
Acta Neurobiol Exp (Wars) ; 82(3): 295-303, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36214712

RESUMO

Caffeine is a psychoactive compound used widely to enhance cognitive functions in human or animal studies. The present study examined the effects of caffeine on cognitive performance and inflammatory factors in mice with medial prefrontal cortex (mPFC) ischemia. Mice underwent a photothrombotic mPFC ischemic stroke and were treated with normal saline or caffeine at different doses intranasally for 7 days. The sham surgery animals received normal saline intranasally. The Morris water maze test and social interaction test were performed to assess spatial and social memories, respectively. In addition, the levels of inflammatory proteins, including tumor necrosis factor­alpha, interleukin­6, and interleukin­10, were measured in the mPFC using immunoblotting. The results showed that mPFC ischemia impaired spatial memory and social behaviors, and caffeine at doses of 0.05 and 0.1 mg improved behavioral outcomes in the ischemic groups. Also, caffeine reversed ischemia­induced high levels of pro­inflammatory biomarkers and enhanced the expression of the anti­inflammatory mediator. Our findings indicate that caffeine alleviated mPFC ischemia­induced memory disturbances, probably through the modulation of the inflammatory mediators.


Assuntos
Cafeína , Disfunção Cognitiva , Administração Intranasal , Animais , Cafeína/farmacologia , Cafeína/uso terapêutico , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Isquemia , Aprendizagem em Labirinto , Camundongos , Camundongos Endogâmicos BALB C , Córtex Pré-Frontal/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
20.
Int Immunopharmacol ; 112: 109295, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36194986

RESUMO

BACKGROUND: Alzheimer's disease (AD) is the most progressive form of neurodegenerative disease resulting in cognitive and non-cognitive deficits. Aluminum is recognized as a risk factor for the etiology, pathogenesis, and progression of AD. The present study was designed to determine the effects of p-coumaric acid (p-CA), a phenolic compound, on spatial cognitive ability and non-cognitive functions and to identify the role of oxidative stress and inflammation in an AD rat model induced by aluminum chloride (AlCl3). METHODS: Both AlCl3 (100 mg/kg/day; P.O.) and p-CA (100 mg/kg/day; P.O.) treatments were given for six consecutive weeks. During the fifth and sixth weeks of the treatment period, the cognitive and non-cognitive functions of the rats were assessed using standard behavioral tests. Additionally, oxidative-antioxidative status, inflammatory markers, and histological changes were evaluated in the cerebral cortex and hippocampal regions of the rats. RESULTS: The results of this study showed that AlCl3 exposure enhanced anxiety-/depression-like behaviors, reduced locomotor/exploratory activities, and impaired spatial learning and memory. These cognitive and non-cognitive disturbances were accompanied by increasing oxidative stress, enhancing inflammatory response, and neuronal loss in the studied brain regions. Interestingly, treatment with p-CA alleviated all the above-mentioned neuropathological changes in the AlCl3-induced AD rat model. CONCLUSION: The findings suggest that both anti-oxidative and anti-inflammatory properties of p-CA may be the underlying mechanisms behind its beneficial effect in preventing neuronal loss and improving cognitive and non-cognitive deficits associated with AD.


Assuntos
Doença de Alzheimer , Doenças Neurodegenerativas , Fármacos Neuroprotetores , Ratos , Animais , Doença de Alzheimer/tratamento farmacológico , Cloreto de Alumínio/efeitos adversos , Alumínio/efeitos adversos , Doenças Neurodegenerativas/tratamento farmacológico , Ratos Wistar , Modelos Animais de Doenças , Estresse Oxidativo , Inflamação/tratamento farmacológico , Inflamação/patologia , Hipocampo , Fármacos Neuroprotetores/farmacologia , Aprendizagem em Labirinto
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