scholarly journals Effects of Chronic Stress on Cognition in Male SAMP8 Mice

2016 ◽  
Vol 39 (3) ◽  
pp. 1078-1086 ◽  
Author(s):  
Jinhua Wang ◽  
Jie Yuan ◽  
Jingjuan Pang ◽  
Jiang Ma ◽  
Bing Han ◽  
...  

Background/Aims: Chronic stress can lead to cognitive impairment. Senescence-accelerated mouse prone 8 (SAMP8) is a naturally occurring animal model that is useful for investigating the neurological mechanisms of Alzheimer's disease. Here we investigated the impact and mechanisms of chronic stress on cognition in male SAMP8 mice. Methods: Male 6-month- old SAMP8 and SAMR1 (senescence-accelerated mouse resistant 1) mice strains were randomly divided into 4 groups. Mice in the unpredictable chronic mild stress (UCMS) groups were exposed to diverse stressors for 4 weeks. Then, these mice performed Morris water maze (MWM) test to assess the effect of UCMS on learning and memory. To explore the neurological mechanisms of UCMS on cognition in mice, we evaluated changes in the expression of postsynaptic density 95 (PSD95) and synaptophysin (SYN), which are essential proteins for synaptic plasticity. Five mice from each group were randomly chosen for reverse transcription polymerase chain reaction (RT-PCR) and western blotting analysis of SYN and PSD95. Results: The Morris water maze experiment revealed that the cognitive ability of the SAMP8 mice decreased with brain aging, and that chronic stress aggravated this cognitive deficit. In addition, chronic stress decreased the mRNA and protein expression of SYN and PSD95 in the hippocampus of the SAMP8 mice; however, the SAMR1 mice were unaffected. Conclusion: Our results demonstrate that decreased cognition and synaptic plasticity are related to aging. Moreover, we show that chronic stress aggravated this cognitive deficit and decreased SYN and PSD95 expression in the SAMP8 mice. Furthermore, the SAMP8 mice were more vulnerable to the detrimental effects of chronic stress on cognition than the SAMR1 mice. Our results suggest that the neurological mechanisms of chronic stress on cognition might be associated with a decrease in hippocampal SYN and PSD95 expression, which is critical for structural synaptic plasticity.

Author(s):  
Kazunori Sasaki ◽  
Noelia Geribaldi-Doldán ◽  
Qingqing Wu ◽  
Julie Davies ◽  
Francis G. Szele ◽  
...  

Much attention has recently been focused on nutraceuticals, with minimal adverse effects, developed for preventing or treating neurological diseases such as Alzheimer's disease (AD). The present study was conducted to investigate the potential effect on neural development and function of the microalgae Aurantiochytrium sp. as a nutraceutical. To test neuroprotection by the ethanol extract of Aurantiochytrium (EEA) and a derivative, the n-Hexane layer of EEA (HEEA), amyloid-β-stimulated SH-SY5Y cells, was used as an in vitro AD model. We then assessed the potential enhancement of neurogenesis by EEA and HEEA using murine ex vivo neurospheres. We also administered EEA or HEEA to senescence-accelerated mouse-prone 8 (SAMP8) mice, a non-transgenic strain with accelerated aging and AD-like memory loss for evaluation of spatial learning and memory using the Morris water maze test. Finally, we performed immunohistochemical analysis for assessment of neurogenesis in mice administered EEA. Pretreatment of SH-SY5Y cells with EEA or the squalene-rich fraction of EEA, HEEA, ameliorated amyloid-β-induced cytotoxicity. Interestingly, only EEA-treated cells showed a significant increase in cell metabolism and intracellular adenosine triphosphate production. Moreover, EEA treatment significantly increased the number of neurospheres, whereas HEEA treatment significantly increased the number of β-III-tubulin+ young neurons and GFAP+ astrocytes. SAMP8 mice were given 50 mg/kg EEA or HEEA orally for 30 days. EEA and HEEA decreased escape latency in the Morris water maze in SAMP8 mice, indicating improved memory. To detect stem cells and newborn neurons, we administered BrdU for 9 days and measured BrdU+ cells in the dentate gyrus, a neurogenic stem cell niche of the hippocampus. In SAMP8 mice, EEA rapidly and significantly increased the number of BrdU+GFAP+ stem cells and their progeny, BrdU+NeuN+ mature neurons. In conclusion, our data in aggregate indicate that EEA and its constituents could be developed into a nutraceutical for promoting brain health and function against several age-related diseases, particularly AD.


Author(s):  
Ewa Zwierzyńska ◽  
Agata Krupa-Burtnik ◽  
Bogusława Pietrzak

Abstract Background Retigabine belongs to the novel generation of antiepileptic drugs but its complex mechanism of action causes that the drug might be effective in other diseases, for instance, alcohol dependence. It is known that ethanol abuse impaired the function of brain structures associated with memory and learning such as the hippocampus. In our previous study, retigabine reduced hippocampal changes induced by ethanol in the EEG rhythms in rabbits. This study is focused on the impact of retigabine on memory processes in male rats receiving alcohol. Methods Memory was evaluated in various experimental models: Morris water maze, Contextual, and Cued Fear Conditioning tests. Retigabine was administered for 3 weeks directly to the stomach via oral gavage at a dose of 10 mg/kg. Rats received also 20% ethanol (5 g/kg/day in two doses) via oral gavage for 3 weeks and had free access to 5% ethanol in the afternoon and at night. Morris water maze was performed after 1 and 3 weeks of ethanol administration and after 1 week from the discontinuation of ethanol administration. Contextual and Cued Fear Conditioning tests were carried out after 24 h and 72 h of alcohol discontinuation. Results The drug significantly decreased ethanol-induced memory disturbances during alcohol administration as well as slightly improved learning processes after the discontinuation of ethanol administration. Conclusions This beneficial effect of retigabine-ethanol interaction on memory may be a relevant element of the drug’s impact on the development of addiction.


2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Jing Jiang ◽  
Gang Liu ◽  
Suhua Shi ◽  
Zhigang Li

Objectives. To compare musical electroacupuncture and electroacupuncture in a mouse model of Alzheimer’s disease.Methods. In this study, 7.5-month-old male senescence-accelerated mouse prone 8 (SAMP8) mice were used as an Alzheimer’s disease animal model. In the normal control paradigm, 7.5-month-old male SAMR1 mice were used as the blank control group (N group). After 15 days of treatment, using Morris water maze test, micro-PET, and immunohistochemistry, the differences among the musical electroacupuncture (MEA), electroacupuncture (EA), Alzheimer’s disease (AD), and normal (N) groups were assessed.Results. The Morris water maze test, micro-PET, and immunohistochemistry revealed that MEA and EA therapies could improve spatial learning and memory ability, glucose metabolism level in the brain, and Aβamyloid content in the frontal lobe, compared with the AD group (P<0.05). Moreover, MEA therapy performed better than EA treatment in decreasing amyloid-beta levels in the frontal lobe of mice with AD.Conclusion. MEA therapy may be superior to EA in treating Alzheimer’s disease as demonstrated in SAMP8 mice.


Author(s):  
Virginie Lam ◽  
Ryusuke Takechi ◽  
Matthew A. Albrecht ◽  
Zachary John D'Alonzo ◽  
Liam Graneri ◽  
...  

2019 ◽  
Vol 9 (9) ◽  
pp. 236 ◽  
Author(s):  
Xue Li ◽  
Lu Wang ◽  
Shuling Zhang ◽  
Xiang Hu ◽  
Huijun Yang ◽  
...  

This study was designed to investigate beneficial effects of swimming exercise training on learning/memory, synaptic plasticity and CREB (cAMP response element binding protein) expression in hippocampus in a rat model of d-galactose-induced aging (DGA). Eighty adult male rats were randomly divided into four groups: Saline Control (group C), DGA (group A), Swimming exercise before DGA (group S1), and Swimming during DGA (group S2). These four groups of animals were further divided into Morris water maze training group (M subgroup) and sedentary control group (N subgroup). Spatial learning/memory was tested using Morris water maze training. The number and density of synaptophysin (Syp) and metabotropic glutamate receptor 1 (mGluR1) in hippocampal dentate gyrus area, CREB mRNA and protein expression and DNA methylation levels were determined respectively with immunohistochemistry, western blot, real-time PCR, and MassArray methylation detection platform. We found that compared with group C, DGA rats showed aging-like poor health and weight loss as well as hippocampal neurodegenerative characteristics. Exercise training led to a time-dependent decrease in average escape latency and improved spatial memory. Exercise training group (S2M) had significantly increased swim distance as compared with controls. These functional improvements in S2M group were associated with higher Syp and mGluR1 values in hippocampus (p < 0.01) as well as higher levels of hippocampal CREB protein/mRNA expression and gene methylation. In conclusion, swimming exercise training selectively during drug-induced aging process protected hippocampal neurons against DGA-elicited degenerative changes and in turn maintained neuronal synaptic plasticity and learning/memory function, possibly through upregulation of hippocampal CREB protein/mRNA and reduction of DGA-induced methylation of CREB.


2020 ◽  
Vol 25 (1) ◽  
pp. 21-35
Author(s):  
Asiye Rafiee Sardooi ◽  
◽  
Parham Reisi ◽  
Azadeh Yazdi ◽  
◽  
...  

Introduction: Chronic stress, which has been prevalent in human life, induce structural changes in the hippocampus. Depression and impairment of memory are serious comorbidities of chronic stress. In this study, we evaluated the impact of an Iranian honey pretreatment on memory deficit, depression and the hippocampal neuronal loss in the chronic unpredictable mild stress (CUMS) model. Methods: Adult male Wistar rats were divided into the control groups that received water or honey (0.2 or 2g/kg) and CUMS groups that subjected different, randomly and unpredictable mild stressors for 4 weeks. Ten days before starting the CUMS procedures, the animals received honey (0.2 or 2g/kg, daily, orally), which was continued until sacrificing. Morris water maze and sucrose performance tests were used to evaluate the spatial learning and memory and depressive-like behavior in the animals respectively. Hippocampus and whole brain samples were collected for further biochemical and histological analysis. Results: Honey reversed the depression-like behavior and ameliorated the spatial memory deficit induced by CUMS. Also, honey decreased cell death in the hippocampus and reduced the malondialdehyde level in treated animals. Conclusion: These results revealed that honey diminished learning and memory deficits and depression in chronic stress conditions.


Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1777
Author(s):  
Anne-Laure Dinel ◽  
Céline Lucas ◽  
Damien Guillemet ◽  
Sophie Layé ◽  
Véronique Pallet ◽  
...  

Background: Two different species of sage, Salvia officinalis and Salvia lavandulaefolia, have demonstrated activities in cognitive function during preclinical and clinical studies related to impaired health situations or single administration. Different memory processes have been described to be significantly and positively impacted. Objective: Our objective is to explore the potential of these Salvia, and their additional activities, in healthy situations, and during prolonged administration, on memory and subsequent mechanisms of action related to putative effects. Design: This mouse study has implicated four investigational arms dedicated to control, Salvia officinalis aqueous extract, Salvia lavandulaefolia-encapsulated essential oil and a mix thereof (Cognivia™) for 2 weeks of administration. Cognitive functions have been assessed throughout Y-maze and Morris water maze models. The impact of supplementation on lipid peroxidation, oxidative stress, neurogenesis, neuronal activity, neurotrophins, neurotrophin receptors, CaM kinase II and glucocorticoid receptors has been assessed via post-interventional tissue collection. Results: All Salvia groups had a significant effect on Y-maze markers on day 1 of administration. Only the mix of two Salvia species demonstrated significant improvements in Morris water maze markers at the end of administration. Considering all biological and histological markers, we did not observe any significant effect of S. officinalis, S. lavandulaefolia and a mix of Salvia supplementation on lipid peroxidation, oxidative stress and neuronal plasticity (neurogenesis, neuronal activity, neurotrophins). Interestingly, CaM kinase II protein expression is significantly increased in animals supplemented with Salvia. Conclusion: The activities of Salvia alone after one intake have been confirmed; however, a particular combination of different types of Salvia have been shown to improve memory and present specific synergistic effects after chronic administration in healthy mice.


Author(s):  
Jia Luo ◽  
Changfa Tang ◽  
Xiaobin Chen ◽  
Zhanbing Ren ◽  
Honglin Qu ◽  
...  

This study was to study the impact of aerobic exercises on the chronic unpredictable mild stress (CUMS) in mice, and to discuss the possible mechanism from the skeletal muscle AMPK/PGC-1α energy metabolism signaling pathway. The healthy male mice were randomly divided into Control Group (CG), Model Group (MG), and Model Exercise Group (ME).Twelve stress methods were adopted for four weeks (28 days) to establish the depression model. ME was subject to aerobic training plan after the model was established. The weight of the mice was recorded weekly. After the experimental intervention, the three groups of mice were subjected to behavioral assessment tests. Western blotting, RT-PCR, and ELISA were performed to test AMPK, p-AMPK, PGC-1α, and ATP in skeletal muscle. There were no significant difference in body weight between the three groups. CUMS leaded to significant decline in behavioral scores. and the p-AMPK and PGC-1α decreased significantly. But boosted ATP content. Aerobic exercise enhanced the expressions of p-AMPK and PGC-1α, increased the ratio of p-AMPK/AMPK, boosted ATP content. And improved behavioral scores significantly. Chronic stress-induced depression-like behavior was improved significantly by Aerobic exercise. The mechanism of aerobic exercise for improving depressive symptoms in mice with chronic stress depression may be related to influence AMPK/PGC-1α pathway.


2010 ◽  
Vol 34 (8) ◽  
pp. S26-S26
Author(s):  
Xuan Zhang ◽  
Ting‑yu Li ◽  
Ke Chen ◽  
Jie Chen ◽  
You‑xue Liu ◽  
...  

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