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1.
J Physiol Sci ; 74(1): 49, 2024 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-39363248

RESUMO

BACKGROUND: Acupuncture can improve herpes simplex encephalitis (HSE), but the underlying mechanism is not clear. Therefore, we evaluated the cognitive function and apoptosis in hippocampus caused by herpes simplex virus type-1 (HSV-1) in rats after acupuncture and described the molecular mechanism. METHODS: Sprague-Dawley rats were induced into HSE models by HSV-1 infection. After 3 days, they received acupuncture at the acupoints of Xuanzhong (GB39), Baihui (GV20), Shenmen (HT7), Shenting (GV24), and Sanyinjiao (SP6), and/or intraperitoneal injection of the p38 MAPK inhibitor SB203580. Morris water maze test was performed on rats. The hippocampus of rats was obtained, and the expression of apoptosis-related genes in the tissues was detected by qRT-PCR. In addition, apoptosis-related proteins and proteins related to the p38 MAPK/CREB pathway in the tissues was detected by western blot. RESULTS: After HSV-1 induction, the rat's escape latency was increased, the time spent on the platform in the target quadrant and the number of platform crossings significantly decreased. In addition, there was an increase in apoptosis in the hippocampus, accompanied by elevated levels of p-p38 and decreased levels of p-CREB. However, these effects could be improved by acupuncture treatment. Interestingly, SB203580 plays a similar role to acupuncture, and acupuncture could further enhance the impacts of SB203580 on cognitive function and apoptosis in hippocampus in HSE rats. CONCLUSION: Acupuncture improves spatial learning and memory impairment caused by HSV-1 in rats. The functional mechanism of acupuncture may be through the p38 MAPK/CREB pathway.


Assuntos
Terapia por Acupuntura , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico , Herpesvirus Humano 1 , Hipocampo , Ratos Sprague-Dawley , Aprendizagem Espacial , Proteínas Quinases p38 Ativadas por Mitógeno , Animais , Ratos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Terapia por Acupuntura/métodos , Masculino , Herpesvirus Humano 1/fisiologia , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Aprendizagem Espacial/fisiologia , Hipocampo/metabolismo , Transtornos da Memória/terapia , Apoptose , Transdução de Sinais , Sistema de Sinalização das MAP Quinases/fisiologia , Encefalite por Herpes Simples/terapia , Aprendizagem em Labirinto/fisiologia , Imidazóis/farmacologia , Piridinas
2.
J Neurochem ; 168(9): 2832-2847, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39361112

RESUMO

Hippocampal neuronal plasticity is a fundamental process underpinning learning and memory formation and requiring elaborate molecular mechanisms that result in the dynamic remodelling of synaptic connectivity. The neurotrophic properties of midkine (Mdk) have been implicated in the development and repair of the nervous system, while Mdk knockout resulted in deficits in the formation of certain types of memory. The role of Mdk in the process of memory-associated neuronal plasticity, however, remains poorly understood. We investigated the learning-induced regulation of Mdk in spatial navigation and association learning using the water maze and the odour reward association learning paradigms, characterising a temporal profile of Mdk protein expression post-learning. Both learning events revealed similar patterns of upregulation of expression of the protein in the rat hippocampal dentate gyrus, which were rapid and transient. Moreover, administration of recombinant Mdk during the endogenous Mdk upregulation following learning enhanced memory in the water maze task revealing a pro-cognitive action of Mdk. We further show that, within the adult hippocampus, Mdk mRNA is predominantly expressed in granular and pyramidal neurons and that hippocampal neuronal Mdk expression is regulated by the canonical plasticity-associated neurotransmitter glutamate. Finally, we confirm that the positive action of Mdk on neurite outgrowth previously noted in cortical and cerebellar neurons extends to hippocampal neurons. Together, our findings suggest a role for Mdk in glutamate-mediated hippocampal neuronal plasticity important for long-term memory consolidation.


Assuntos
Hipocampo , Memória , Midkina , Recompensa , Regulação para Cima , Animais , Midkina/metabolismo , Masculino , Regulação para Cima/fisiologia , Ratos , Hipocampo/metabolismo , Memória/fisiologia , Aprendizagem por Associação/fisiologia , Aprendizagem em Labirinto/fisiologia , Plasticidade Neuronal/fisiologia , Aprendizagem Espacial/fisiologia , Ratos Sprague-Dawley
3.
Science ; 385(6713): 1111-1115, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39236187

RESUMO

Cognitive abilities are hypothesized to affect survival and life span in nonhuman animals. However, most tests of this hypothesis have relied on interspecific comparisons of indirect measures of cognitive ability, such as brain size. We present direct evidence that individual variation in cognitive abilities is associated with differences in life span in a wild food caching bird. We measured the spatial cognitive abilities and tracked the life span of 227 mountain chickadees (Poecile gambeli) in their natural environment and found that individuals with better spatial learning and memory abilities involved in food caching lived longer. These results confirm that enhanced cognitive abilities can be associated with longer life in wild animals and that selection on cognitive abilities can lead to increased life span.


Assuntos
Cognição , Comportamento Alimentar , Longevidade , Aves Canoras , Aprendizagem Espacial , Memória Espacial , Animais , Masculino , Memória , Aves Canoras/fisiologia
4.
eNeuro ; 11(9)2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39284675

RESUMO

Learning to solve a new problem involves identifying the operating rules, which can be accelerated if known rules generalize in the new context. We ask how prior experience affects learning a new rule that is distinct from known rules. We examined how rats learned a new spatial navigation task after having previously learned tasks with different navigation rules. The new task differed from the previous tasks in spatial layout and navigation rule. We found that experience history did not impact overall performance. However, by examining navigation choice sequences in the new task, we found experience-dependent differences in exploration patterns during early stages of learning, as well as differences in the types of errors made during stable performance. The differences were consistent with the animals adopting experience-dependent memory strategies to discover and implement the new rule. Our results indicate prior experience shapes the strategies for solving novel problems, and the impact of prior experience remains persistent.


Assuntos
Ratos Long-Evans , Aprendizagem Espacial , Animais , Aprendizagem Espacial/fisiologia , Masculino , Navegação Espacial/fisiologia , Ratos , Comportamento Exploratório/fisiologia
5.
In Vivo ; 38(5): 2190-2196, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39187339

RESUMO

BACKGROUND/AIM: In a previous report, our group showed that oral administration of lipopolysaccharides (LPS) from Pantoea agglomerans can prevent the progression of streptozotocin (STZ)-induced diabetes-related cognitive dysfunction (DRCD) in mice without causing significant side-effects. However, the treatment effects of oral administration of LPS to DRCD remain unknown. MATERIALS AND METHODS: We modified our previous animal experimental model to investigate whether oral administration of LPS can recover cognitive function after DRCD onset. RESULTS: The Morris water maze (MWM) revealed a significant decrease in learning and memory abilities at 13 days after intracerebroventricular administration of STZ, thereby providing evidence of the occurrence of DRCD in the animal model. Oral administration of LPS (1 mg/kg per day) started after cognitive impairment was observed. After 28 days of treatment, mice receiving LPS via the oral route showed significant recovery of spatial learning ability, a symptom of early dementia, while only a trend toward recovery was seen for spatial memory compared to the untreated group. CONCLUSION: These results, limited to MWM, suggest that oral administration of LPS is a promising therapeutic strategy for restoring decreased spatial learning ability.


Assuntos
Disfunção Cognitiva , Diabetes Mellitus Experimental , Modelos Animais de Doenças , Lipopolissacarídeos , Aprendizagem em Labirinto , Aprendizagem Espacial , Animais , Lipopolissacarídeos/efeitos adversos , Lipopolissacarídeos/administração & dosagem , Camundongos , Administração Oral , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/tratamento farmacológico , Masculino , Diabetes Mellitus Experimental/complicações , Aprendizagem Espacial/efeitos dos fármacos , Aprendizagem em Labirinto/efeitos dos fármacos , Estreptozocina/administração & dosagem
6.
PLoS One ; 19(8): e0307551, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39197002

RESUMO

The effect of hibernation on cognitive capacities of individuals is not fully understood, as studies provide conflicting results. Most studies focus on behavioural observations without taking the physiological state of individuals to account. To mechanistically understand the effect of hibernation on the brain, physiological parameters need to be included. The implantation of bio-loggers can provide insights on i.e. body temperature without further manipulation of the animals. Surgeries and anaesthesia, however, can harm animals' health and cause cognitive dysfunction, potentially biasing data collected through bio-loggers. We investigated the effects of bio-logger implantation surgery on cognitive performance and learning, controlling for animal and study design characteristics. First, juvenile dormice successfully learned to solve a spatial cognition task using a vertical maze. Distance, transitions, velocity, and duration were measured as indicators for performance. After training, bio-loggers were implanted intra-abdominally under general anaesthesia. Animals were re-tested in the maze two weeks after. We found no effect of bio-logger implantation and surgery on performance. This study is the first to show spatial cognition learning in edible dormice and provides a full description of the peri-anaesthetic management and a protocol for bio-logger implantation surgery in dormice. Importantly, measures were taken to mitigate common anaesthetic complications that could lead to post-operative cognitive dysfunction and influence animal behaviour. By pairing physiological measurements through bio-logger implantation with behaviour and cognition measurements, future research will significantly advance the understanding on mechanisms of learning and behaviour.


Assuntos
Anestesia Geral , Cognição , Hibernação , Animais , Cognição/fisiologia , Hibernação/fisiologia , Aprendizagem em Labirinto , Aprendizagem Espacial , Masculino
7.
Cogn Process ; 25(Suppl 1): 61-66, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39123056

RESUMO

Maps have been invaluable navigation aids for millennia and thus have been critical for human survival. The increasing popularity of and high dependence on digital, location-aware assistive navigation technology, however, has been shown to divert our attention from the environment and to negatively influence innate spatial abilities. To mitigate this, neuroadaptive mobile geographic information displays (namGIDs) are proposed that respond in real-time to navigators' cognitive task demands and wayfinder's situated visuo-spatial attention needs. In doing so, namGIDs may not only help navigators maintain navigation efficiency but more importantly, also continuously scaffold spatial learning. To do this, the proposed navigation assistance must strike the appropriate balance between welcomed mobility efficiency gains while limiting human spatial deskilling. Leveraging neuroadaptive cartography, we can ensure to remain effective navigators, empowered to explore the world with confidence.


Assuntos
Navegação Espacial , Humanos , Navegação Espacial/fisiologia , Percepção Espacial/fisiologia , Atenção/fisiologia , Aprendizagem Espacial/fisiologia , Adaptação Fisiológica/fisiologia , Sistemas de Informação Geográfica
8.
Iran J Med Sci ; 49(7): 441-449, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39114632

RESUMO

Background: Alzheimer's disease (AD) is a neurodegenerative condition characterized by gradual cognitive impairment, including loss of synapses and nerve cells involved in learning, memory, and habit formation processes. Bone Marrow Mesenchymal Stem Cells (BM-MSCs) are multipotent cells. Because of their self-renewable, differentiation, and immunomodulatory capabilities, they are commonly used to treat many disorders. Hence, the current study intends to examine the effect of BM-MSCs transplantation on Aluminum chloride (AlCl3)-induced cognitive problems, an experimental model resembling AD's hallmarks in rats. Methods: The study was conducted in 2022 at The Biomedical Laboratory Faculty of Medicine, Andalas University, Indonesia. Adult male Wistar rats (three groups: negative control; no intervention+treatment with PBS; positive control: AlCl3+treatment with aqua dest; AlCl3+BM-MSCs: AlCl3+treatment with BM-MSCs, n=5 each) were treated daily with AlCl3 orally for five days. Stem cells were intraperitoneally injected into rats at a dose of 1x106 cells/rat. The same quantity of phosphate-buffered saline was given to the control group. One month after stem cell injection, the rat brain tissue was removed and placed in the film bottles that had been created. The expression of neural progenitor cell markers, including nestin and sex-determining Y-box 2 (SOX-2), was analyzed using real-time polymerase chain reaction (RT-PCR). Rats' cognitive and functional memory were examined using Y-maze. Data were analyzed using SPSS software (version 26.0) with a one-way analysis of variance (ANOVA) test. Results: The gene expression of nestin (29.74±0.42), SOX-2 (31.44±0.67), and percent alternation of Y-maze (67.04±2.28) increased in the AlCl3+BM-MSCs group compared to that in the positive control group. RT-PCR analysis indicated that nestin (P<0.001) and SOX-2 (P<0.001) were significantly enhanced in the AlCl3+BM-MSCs group compared to the positive control group. This group also indicated an increased percent alternation of Y-maze (P<0.001) in the AlCl3+BM-MSCs group compared to the positive control group. Conclusion: Due to its potential effects on cell therapy, BM-MSCs were found effective in a rat model of AD on the impairment of the rats' behavior and increased expression of neural progenitor cell markers.


Assuntos
Cloreto de Alumínio , Doença de Alzheimer , Modelos Animais de Doenças , Células-Tronco Mesenquimais , Nestina , Ratos Wistar , Fatores de Transcrição SOXB1 , Animais , Cloreto de Alumínio/farmacologia , Ratos , Masculino , Doença de Alzheimer/terapia , Nestina/genética , Transplante de Células-Tronco Mesenquimais/métodos , Compostos de Alumínio/farmacologia , Aprendizagem Espacial/efeitos dos fármacos , Aprendizagem Espacial/fisiologia , Cloretos , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia
9.
Neuropharmacology ; 259: 110108, 2024 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-39128582

RESUMO

Consumption of saturated fat-enriched diets during adolescence has been closely associated with the reduction of hippocampal synaptic plasticity and the impairment of cognitive function. Nevertheless, the effect of long-term intake of these foods has not yet been studied. In the present study, we have investigated the effect of a treatment, lasting for 40 weeks, with a diet enriched in saturated fat (SOLF) on i) spatial learning and memory, ii) hippocampal synaptic transmission and plasticity, and iii) hippocampal gene expression levels in aged male and female mice. Our findings reveal that SOLF has a detrimental impact on spatial memory and synaptic plasticity mechanisms, such as long-term potentiation (LTP), and downregulates Gria1 expression specifically in males. In females, SOLF downregulates the gene expression of Gria1/2/3 and Grin1/2A/2B glutamate receptor subunits as well as some proinflammatory interleukins. These findings highlight the importance of considering sex-specific factors when assessing the long-term effects of high-fat diets on cognition and brain plasticity.


Assuntos
Dieta Hiperlipídica , Hipocampo , Caracteres Sexuais , Animais , Masculino , Feminino , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Dieta Hiperlipídica/efeitos adversos , Camundongos , Camundongos Endogâmicos C57BL , Plasticidade Neuronal/efeitos dos fármacos , Plasticidade Neuronal/fisiologia , Aprendizagem Espacial/efeitos dos fármacos , Aprendizagem Espacial/fisiologia , Receptores de AMPA/metabolismo , Memória Espacial/efeitos dos fármacos , Memória Espacial/fisiologia , Memória/efeitos dos fármacos , Memória/fisiologia , Potenciação de Longa Duração/efeitos dos fármacos , Potenciação de Longa Duração/fisiologia , Receptores de N-Metil-D-Aspartato/metabolismo , Transmissão Sináptica/efeitos dos fármacos , Transmissão Sináptica/fisiologia , Gorduras na Dieta/farmacologia
10.
Brain Behav Immun ; 122: 58-74, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39128568

RESUMO

BACKGROUND: During aging, both the brain and the immune system undergo a progressive impairment of physiological functions. Microglia, the immunocompetent cells of the central nervous system, shift towards a chronic mild inflammatory state that impacts brain homeostasis. Extracellular vesicles (EVs) released by microglia transport packages of molecular information that mirror the inflammatory status of donor cells and modulate the inflammatory phenotype of recipient microglia and other cell types. RESULTS: We demonstrated that intranasal administration of EVs derived from microglial-like BV2 cells to late adult mice (16-20 months of age) shifts microglia toward a "juvenile" morphology affecting their inflammatory profile. Mice treated with BV2-derived EVs have a reduction of anxiety-like behavior and an increased spatial learning, with sex-dependent differences. Further, BV2-derived EVs increased neuronal plasticity both in male and female mice. These findings suggest the involvement of microglial cells in vesicles-mediated anti-aging effect. CONCLUSIONS: Our data indicate that BV2-derived EVs could represent a resource to slow down age-dependent inflammation in the mouse brain.


Assuntos
Envelhecimento , Encéfalo , Vesículas Extracelulares , Inflamação , Microglia , Plasticidade Neuronal , Animais , Vesículas Extracelulares/metabolismo , Microglia/metabolismo , Camundongos , Plasticidade Neuronal/fisiologia , Feminino , Masculino , Inflamação/metabolismo , Encéfalo/metabolismo , Envelhecimento/metabolismo , Comportamento Animal/fisiologia , Camundongos Endogâmicos C57BL , Ansiedade/metabolismo , Aprendizagem Espacial/fisiologia , Administração Intranasal
11.
Neurochem Int ; 179: 105834, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39142353

RESUMO

Alcohol exposure in adolescence is considered a major cause of cognitive impairments later in life including spatial learning and memory. Integrated stress response (ISR), a program of conservative translation and transcription, is crucial in synaptic plasticity and memory. Although previous studies have elucidated ISR in different brain areas involved in learning and memory disorders, the impact of ISR on learning and memory following adolescent alcohol exposure remains unclear. Here, we demonstrated that adolescent intermittent ethanol (AIE) exposure caused spatial learning and memory impairment, combined with neuronal damage in the medial prefrontal cortex (mPFC), nucleus accumbens (NAc) and hippocampus (HIP) in adult rats. Moreover, integrated stress response inhibitor (ISRIB) administration not only improved spatial learning and memory impairment and neuronal damage but also inhibited the endoplasmic reticulum stress (ER) and reversed changes in synaptic proteins. These findings suggested that ISRIB ameliorates AIE exposure-induced spatial learning and memory deficits by improving neural morphology and synaptic function through inhibiting ER stress signaling pathway in the mPFC, NAc and HIP in adulthood. Our findings may enhance comprehension of cognitive function and neuronal effects of adolescent ethanol exposure and ISRIB treatment may be an underlying potential option for addressing alcohol-induced learning and memory deficits.


Assuntos
Etanol , Transtornos da Memória , Ratos Sprague-Dawley , Aprendizagem Espacial , Animais , Masculino , Etanol/toxicidade , Etanol/administração & dosagem , Ratos , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/tratamento farmacológico , Transtornos da Memória/metabolismo , Aprendizagem Espacial/efeitos dos fármacos , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia
12.
Biomed Pharmacother ; 179: 117350, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39197189

RESUMO

Rosemary (Rosmarinus officinalis L.) is a rich source of dietary bioactive compounds such as rosmarinic acid and carnosol with a large repertoire of pharmacological properties, including anti-inflammatory and neuroprotective activities. In the present study, we investigated rosemary as a potential new therapeutic agent for cognitive function and other symptoms of aging. In this present study, we have aimed to investigate the effects of oral administration of rosemary extract (RME) on learning and memory in the context of other biomarkers-related cognitive function and neurotransmitter levels in senescent accelerated prone 8 (SAMP8) mouse, a model of accelerating aging and Alzheimer's disease. The Morris water maze (MWM) test showed improved spatial learning and memory behavior in RME treated SAMP8 mouse. Moreover, RME decreased Aß42 and inflammatory cytokine levels and increased BDNF, Sirt1, and neurotransmitter levels in SAMP8 mouse. Whole-genome microarray analysis revealed that RME significantly increased gene expression related to oligodendrocyte differentiation, myelination, and ATP production in the hippocampus and decreased gene expression related to stress, neuroinflammation, and apoptosis. Also, in the SAMP8 hippocampus, RME significantly increased Olig1 and Olig2 expression. Altogether, our study is the first to report improvement of spatial learning and memory of RME, modulation of genes important for oligodendrogenesis, and Anti-neuroinflammatory effect by suppressing Aß42 levels in mouse brain and thus highlights the prospects of RME in the treatment of cognitive dysfunction and aging.


Assuntos
Encéfalo , Memória , Oligodendroglia , Extratos Vegetais , Rosmarinus , Animais , Extratos Vegetais/farmacologia , Rosmarinus/química , Camundongos , Memória/efeitos dos fármacos , Masculino , Oligodendroglia/efeitos dos fármacos , Oligodendroglia/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Aprendizagem em Labirinto/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/genética , Aprendizagem Espacial/efeitos dos fármacos , Cognição/efeitos dos fármacos , Modelos Animais de Doenças
13.
Sci Rep ; 14(1): 15944, 2024 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-38987437

RESUMO

Assessment of spatial learning abilities is central to behavioral neuroscience and a useful tool for animal model validation and drug development. However, biases introduced by the apparatus, environment, or experimentalist represent a critical challenge to the test validity. We have recently developed the Modified Barnes Maze (MBM) task, a spatial learning paradigm that overcomes inherent behavioral biases of animals in the classical Barnes maze. The specific combination of spatial strategies employed by mice is often considered representative of the level of cognitive resources used. Herein, we have developed a convolutional neural network-based classifier of exploration strategies in the MBM that can effectively provide researchers with enhanced insights into cognitive traits in mice. Following validation, we compared the learning performance of female and male C57BL/6J mice, as well as that of Ts65Dn mice, a model of Down syndrome, and 5xFAD mice, a model of Alzheimer's disease. Male mice exhibited more effective navigation abilities than female mice, reflected in higher utilization of effective spatial search strategies. Compared to wildtype controls, Ts65Dn mice exhibited delayed usage of spatial strategies despite similar success rates in completing this spatial task. 5xFAD mice showed increased usage of non-spatial strategies such as Circling that corresponded to higher latency to reach the target and lower success rate. These data exemplify the need for deeper strategy classification tools in dissecting complex cognitive traits. In sum, we provide a machine-learning-based strategy classifier that extends our understanding of mice's spatial learning capabilities while enabling a more accurate cognitive assessment.


Assuntos
Aprendizagem em Labirinto , Camundongos Endogâmicos C57BL , Redes Neurais de Computação , Aprendizagem Espacial , Animais , Masculino , Feminino , Camundongos , Aprendizagem Espacial/fisiologia , Modelos Animais de Doenças , Doença de Alzheimer , Comportamento Animal
14.
Sci Rep ; 14(1): 15996, 2024 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-38987609

RESUMO

Alzheimer's disease (AD) is a neurological condition that is connected with a decline in a person's memory as well as their cognitive ability. One of the key topics of AD research has been the exploration of metabolic causes. We investigated the effects of treadmill exercise and intranasal insulin on learning and memory impairment and the expression of IGF1, BDNF, and GLUT4 in hypothalamus. The animals were put into 9 groups at random. In this study, we examined the impact of insulin on spatial memory in male Wistar rats and analyzed the effects of a 4-week pretreatment of moderate treadmill exercise and insulin on the mechanisms of improved hypothalamic glucose metabolism through changes in gene and protein expression of IGF1, BDNF, and GLUT4. We discovered that rat given Aß25-35 had impaired spatial learning and memory, which was accompanied by higher levels of Aß plaque burden in the hippocampus and lower levels of IGF1, BDNF, and GLUT4 mRNA and protein expression in the hypothalamus. Additionally, the administration of exercise training and intranasal insulin results in the enhancement of spatial learning and memory impairments, the reduction of plaque burden in the hippocampus, and the enhancement of the expression of IGF1, BDNF, and GLUT4 in the hypothalamus of rats that were treated with Aß25-35. Our results show that the improvement of learning and spatial memory due to the improvement of metabolism and upregulation of the IGF1, BDNF, and GLUT4 pathways can be affected by pretreatment exercise and intranasal insulin.


Assuntos
Doença de Alzheimer , Modelos Animais de Doenças , Transportador de Glucose Tipo 4 , Hipotálamo , Fator de Crescimento Insulin-Like I , Insulina , Condicionamento Físico Animal , Ratos Wistar , Transdução de Sinais , Animais , Doença de Alzheimer/metabolismo , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/terapia , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Insulina/metabolismo , Ratos , Hipotálamo/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transportador de Glucose Tipo 4/metabolismo , Transportador de Glucose Tipo 4/genética , Peptídeos beta-Amiloides/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/genética , Hipocampo/metabolismo , Hipocampo/efeitos dos fármacos , Administração Intranasal , Fragmentos de Peptídeos , Memória Espacial/efeitos dos fármacos , Aprendizagem Espacial/efeitos dos fármacos
15.
Horm Behav ; 164: 105598, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38968677

RESUMO

Estrogens have inconsistent effects on learning and memory in both the clinical and preclinical literature. Preclinical literature has the advantage of investigating an array of potentially important factors contributing to the varied effects of estrogens on learning and memory, with stringently controlled studies. This study set out to identify specific factors in the animal literature that influence the effects of estrogens on cognition, for possible translation back to clinical practice. The literature was screened and studies meeting strict inclusion criteria were included in the analysis. Eligible studies included female ovariectomized rodents with an adequate vehicle for the estrogen treatment, with an outcome of spatial learning and memory in the Morris water maze. Training days of the Morris water maze were used to assess acquisition of spatial learning, and the probe trial was used to evaluate spatial memory recall. Continuous outcomes were pooled using a random effects inverse variance method and reported as standardized mean differences with 95 % confidence intervals. Subgroup analyses were developed a priori to assess important factors. The overall analysis favoured treatment for the later stages of training and for the probe trial. Factors including the type of estrogen, route, schedule of administration, age of animals, timing relative to ovariectomy, and duration of treatment were all found to be important. The subgroup analyses showed that chronic treatment with 17ß-estradiol, either cyclically or continuously, to young animals improved spatial recall. These results, observed in animals, can inform and guide further clinical research on hormone replacement therapy for cognitive benefits.


Assuntos
Estrogênios , Aprendizagem Espacial , Memória Espacial , Animais , Feminino , Estradiol/farmacologia , Estradiol/administração & dosagem , Estrogênios/farmacologia , Estrogênios/administração & dosagem , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Memória/efeitos dos fármacos , Memória/fisiologia , Ovariectomia , Roedores/fisiologia , Aprendizagem Espacial/efeitos dos fármacos , Aprendizagem Espacial/fisiologia , Memória Espacial/efeitos dos fármacos , Memória Espacial/fisiologia
16.
Neuroscience ; 556: 86-95, 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39047971

RESUMO

As a new means of brain neuroregulation and research, transcranial magneto-acoustic stimulation (TMAS) uses the coupling effect of ultrasound and a static magnetic field to regulate neural activity in the corresponding brain areas. Calcium ions can promote the secretion of neurotransmitters and play a key role in the transmission of neural signals in brain cognition. In this study, to explore the effects of TMAS on cognitive function and neural signaling in the CA1 region of the hippocampus, TMAS was applied to male 2-month-old C57 mice with a magnetic field strength of 0.3 T and ultrasound intensity of 2.6 W/cm2. First, the efficiency of neural signaling in the CA1 region of the mouse hippocampus was detected by fiber photometry. Second, the effects of TMAS on cognitive function in mice were investigated through multiple behavioral experiments, including spatial learning and memory ability, anxiety and desire for novelty. The experimental results showed that TMAS could improve cognitive function in mice, and the efficiency of neural signaling in the CA1 area of the hippocampus was significantly increased during stimulation and maintained for one week after stimulation. In addition, the neural signaling efficiency in the CA1 area of the hippocampus increased in the open field (OF) experiment and recovered after one week, the neural signaling efficiency in the new object exploration (NOE) experiment was significantly enhanced, and the intensity slowed after one week. In conclusion, TMAS enhances cognitive performance and promotes neural signaling in the CA1 region of the mouse hippocampus.


Assuntos
Estimulação Acústica , Região CA1 Hipocampal , Cognição , Camundongos Endogâmicos C57BL , Animais , Região CA1 Hipocampal/fisiologia , Cognição/fisiologia , Masculino , Camundongos , Estimulação Magnética Transcraniana/métodos , Aprendizagem Espacial/fisiologia , Memória/fisiologia
17.
Brain Behav ; 14(7): e3614, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38988101

RESUMO

PURPOSE: Levothyroxine (LEV) monotherapy cannot completely improve cognitive and behavioral impairments induced by hypothyroidism, whereas a combination therapy of exercise and LEV may ameliorate these deficits. This study aimed to determine the effects of mild-intensity forced exercise and LEV treatment on the anxiety profile and cognitive functions in male offspring of hypothyroid dams. METHOD: Twenty-four female rats (mothers) were randomly divided into sham (healthy) and hypothyroidism groups and then placed with male rats to mate. The presence of vaginal plaque confirmed pregnancy (gestational day, GD 0). 6-propyl-2-thiouracil (PTU, 100 ppm) was added to the drinking water of the hypothyroidism group from GD 6 to the 21st postnatal day (PND). The sham group received tap water. On PND 21, serum T4 levels of mothers, and 10 pups were measured to confirm hypothyroidism. Sixty-four male pups were left undisturbed for 30 days and then were divided into eight groups that received saline or LEV (50 µg/kg, i.p.) with or without forced mild-intensity exercise. After 14 days of interventions, anxiety-like behaviors, spatial learning and memory, and hippocampal brain-derived neurotrophic factor (BDNF) levels were evaluated. FINDING: A pre and postnatal PTU-induced model of hypothyroidism increased anxiety-like behaviors, impaired spatial learning and memory, and decreased hippocampal BDNF levels in male offspring rats. LEV alone increased BDNF levels and improved spatial learning. Exercise alone increased BDNF levels, improved spatial learning and memory, and decreased anxiety-like behaviors. Exercise plus LEV more effectively improved anxiety-like behaviors and spatial learning than exercise or LEV alone. CONCLUSION: Practically, these pre-clinical findings highlight the importance of the combination of exercise and LEV regimen in treating patients with hyperthyroidism.


Assuntos
Ansiedade , Fator Neurotrófico Derivado do Encéfalo , Hipocampo , Hipotireoidismo , Condicionamento Físico Animal , Tiroxina , Animais , Hipotireoidismo/tratamento farmacológico , Hipotireoidismo/metabolismo , Hipotireoidismo/terapia , Hipotireoidismo/fisiopatologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Masculino , Tiroxina/farmacologia , Tiroxina/administração & dosagem , Ratos , Ansiedade/terapia , Ansiedade/etiologia , Ansiedade/tratamento farmacológico , Hipocampo/metabolismo , Hipocampo/efeitos dos fármacos , Feminino , Condicionamento Físico Animal/fisiologia , Gravidez , Ratos Wistar , Efeitos Tardios da Exposição Pré-Natal/terapia , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Aprendizagem Espacial/efeitos dos fármacos , Aprendizagem Espacial/fisiologia , Terapia Combinada , Propiltiouracila/farmacologia , Propiltiouracila/administração & dosagem
18.
Nat Commun ; 15(1): 6410, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39080283

RESUMO

Adult neurogenesis is a unique form of neuronal plasticity in which newly generated neurons are integrated into the adult dentate gyrus in a process that is modulated by environmental stimuli. Adult-born neurons can contribute to spatial memory, but it is unknown whether they alter neural representations of space in the hippocampus. Using in vivo two-photon calcium imaging, we find that male and female mice previously housed in an enriched environment, which triggers an increase in neurogenesis, have increased spatial information encoding in the dentate gyrus. Ablating adult neurogenesis blocks the effect of enrichment and lowers spatial information, as does the chemogenetic silencing of adult-born neurons. Both ablating neurogenesis and silencing adult-born neurons decreases the calcium activity of dentate gyrus neurons, resulting in a decreased amplitude of place-specific responses. These findings are in contrast with previous studies that suggested a predominantly inhibitory action for adult-born neurons. We propose that adult neurogenesis improves representations of space by increasing the gain of dentate gyrus neurons and thereby improving their ability to tune to spatial features. This mechanism may mediate the beneficial effects of environmental enrichment on spatial learning and memory.


Assuntos
Giro Denteado , Hipocampo , Neurogênese , Neurônios , Memória Espacial , Animais , Neurogênese/fisiologia , Masculino , Feminino , Giro Denteado/fisiologia , Giro Denteado/citologia , Camundongos , Neurônios/fisiologia , Neurônios/metabolismo , Hipocampo/fisiologia , Hipocampo/citologia , Hipocampo/metabolismo , Memória Espacial/fisiologia , Camundongos Endogâmicos C57BL , Plasticidade Neuronal/fisiologia , Cálcio/metabolismo , Aprendizagem Espacial/fisiologia
19.
J Psychiatr Res ; 177: 169-176, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39024741

RESUMO

BACKGROUND: Cognitive deficits in patients with schizophrenia have drawn widespread attention. Transcranial direct current stimulation (tDCS) can modulate cognitive processes by altering neuronal excitability. Previous studies have found that interim testing can enhance spatial route learning and memory in patients with schizophrenia. However, there has been limited research on the combined effects of these two methods on spatial route learning in these patients. OBJECTIVE: To investigate whether the combination of tDCS and interim testing can effectively contribute to the maintenance of spatial route memory in patients with schizophrenia. The study involved conducting route learning using interim testing after anodal tDCS treatment on the left dorsolateral prefrontal cortex (L-DLPFC). METHODS: Ninety-two patients with schizophrenia were recruited and divided into groups receiving anodal, sham, or no stimulation. The anodal group received L-DLPFC tDCS treatment 10 times over 5 days (twice daily for 20 min). After treatment, spatial route learning was assessed in interim testing. Correct recall rates of landmark positions and proactive interference from prior learning were compared among the groups. RESULTS: Regardless of stimulation type, the interim testing group outperformed the relearning group. Additionally, recall scores were higher following anodal stimulation, indicating the efficacy of tDCS. CONCLUSIONS: Both tDCS and interim testing independently enhance the ability to learn new information in spatial route learning for patients with schizophrenia, indicating that tDCS of the left DLPFC significantly improves memory in these patients.


Assuntos
Esquizofrenia , Estimulação Transcraniana por Corrente Contínua , Humanos , Esquizofrenia/terapia , Esquizofrenia/fisiopatologia , Masculino , Feminino , Adulto , Córtex Pré-Frontal Dorsolateral/fisiologia , Adulto Jovem , Aprendizagem Espacial/fisiologia , Rememoração Mental/fisiologia , Pessoa de Meia-Idade
20.
Eur J Neurosci ; 60(3): 4346-4361, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38858126

RESUMO

Mild-moderate traumatic brain injuries (TBIs) are prevalent, and while many individuals recover, there is evidence that a significant number experience long-term health impacts, including increased vulnerability to neurodegenerative diseases. These effects are influenced by other risk factors, such as cardiovascular disease. Our study tested the hypothesis that a pre-injury reduction in cerebral blood flow (CBF), mimicking cardiovascular disease, worsens TBI recovery. We induced bilateral carotid artery stenosis (BCAS) and a mild-moderate closed-head TBI in male and female mice, either alone or in combination, and analyzed CBF, spatial learning, memory, axonal damage, and gene expression. Findings showed that BCAS and TBI independently caused a ~10% decrease in CBF. Mice subjected to both BCAS and TBI experienced more significant CBF reductions, notably affecting spatial learning and memory, particularly in males. Additionally, male mice showed increased axonal damage with both BCAS and TBI compared to either condition alone. Females exhibited spatial memory deficits due to BCAS, but these were not worsened by subsequent TBI. Gene expression analysis in male mice highlighted that TBI and BCAS individually altered neuronal and glial profiles. However, the combination of BCAS and TBI resulted in markedly different transcriptional patterns. Our results suggest that mild cerebrovascular impairments, serving as a stand-in for preexisting cardiovascular conditions, can significantly worsen TBI outcomes in males. This highlights the potential for mild comorbidities to modify TBI outcomes and increase the risk of secondary diseases.


Assuntos
Lesões Encefálicas Traumáticas , Estenose das Carótidas , Circulação Cerebrovascular , Animais , Feminino , Masculino , Lesões Encefálicas Traumáticas/fisiopatologia , Camundongos , Circulação Cerebrovascular/fisiologia , Estenose das Carótidas/fisiopatologia , Camundongos Endogâmicos C57BL , Caracteres Sexuais , Fatores Sexuais , Memória Espacial/fisiologia , Modelos Animais de Doenças , Aprendizagem Espacial/fisiologia
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