Effects of Chronic Stress on Cognition in Male SAMP8 Mice

Wang, Jinhua; Yuan, Jing; Pang, Jingjuan; Ma, Jiang; Han, Bing; Geng, Yichao; Shen, Li; Wang, Hualong; Ma, Qing; Wang, Yanyong; Wang, Mingwei

doi:10.1159/000447816

Cited by 38 publications

(33 citation statements)

References 55 publications

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“…Before our study, several studies reported that aging as chronic stress affect similarly hippocampus function as learning and memory (Tronche et al, 2010; Bonhomme et al, 2014; Wang et al, 2016), then we hypothesized that the modifications of hippocampus transcriptome induced by hypergravity should be similar to those observed in aged mice and/or mice treated with corticosterone.…”

Section: Discussionmentioning

confidence: 92%

Changes in C57BL6 Mouse Hippocampal Transcriptome Induced by Hypergravity Mimic Acute Corticosterone-Induced Stress

Pulga¹,

Porte²,

Morel³

2016

Front. Mol. Neurosci.

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Centrifugation is a widely used procedure to study the impact of altered gravity on Earth, as observed during spaceflights, allowing us to understand how a long-term physical constraint can condition the mammalian physiology. It is known that mice, placed in classical cages and maintained during 21 days in a centrifuge at 3G gravity level, undergo physiological adaptations due to hypergravity, and/or stress. Indeed, an increase of corticosterone levels has been previously measured in the plasma of 3G-exposed mice. Corticosterone is known to modify neuronal activity during memory processes. Although learning and memory performances cannot be assessed during the centrifugation, literature largely described a large panel of proteins (channels, second messengers, transcription factors, structural proteins) which expressions are modified during memory processing. Thus, we used the Illumina technology to compare the whole hippocampal transcriptome of three groups of C57Bl6/J mice, in order to gain insights into the effects of hypergravity on cerebral functions. Namely, a group of 21 days 3G-centrifuged mice was compared to (1) a group subjected to an acute corticosterone injection, (2) a group receiving a transdermal chronic administration of corticosterone during 21 days, and (3) aged mice because aging could be characterized by a decrease of hippocampus functions and memory impairment. Our results suggest that hypergravity stress induced by corticosterone administration and aging modulate the expression of genes in the hippocampus. However, the modulations of the transcriptome observed in these conditions are not identical. Hypergravity affects per-se the hippocampus transcriptome and probably modifies its activity. Hypergravity induced changes in hippocampal transcriptome were more similar to acute injection than chronic diffusion of corticosterone or aging.

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Section: Discussionmentioning

confidence: 92%

Changes in C57BL6 Mouse Hippocampal Transcriptome Induced by Hypergravity Mimic Acute Corticosterone-Induced Stress

Pulga¹,

Porte²,

Morel³

2016

Front. Mol. Neurosci.

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“…The stressors included 1) food deprivation for 24 h, 2) water deprivation for 24 h with an empty bottle for the last 1 h, 3) overnight illumination, 4) removal sawdust for 24 h, 5) soiled cage (200 ml of water in 100 g of sawdust bedding) for 24 h, 6) forced swimming at 8 °C for 6 min, 7) tail nipping (1 cm from the tip of the tail), and 8) physical restraint for 2 h. Different stressors were applied in a pseudo-random manner each day, with the sequence of stressors changed weekly. The detailed process was shown in our previously paper [10]. …”

Section: Methodsmentioning

confidence: 99%

“…Many experiments have established that chronic stress is a risk factor for the development of cognitive deficits, especially for Alzheimer’s disease (AD). Chronic stress not only impaired the early long- term potentiation (LTP) in the at-risk rat model of AD [9], but it also decreased hippocampal synaptic plasticity [10] and increased amyloid-β plaque deposition in Tg2576 mice [11]. Furthermore, our previous study also confirmed that chronic stress exposure increased the levels of glucocorticoids (1.5-fold), promoted senile plaque deposition, neuronal injury, and cognitive impairment in APP/PS1 mice compared to wild-type mice [12]; however, the cognition-related metabolic mechanisms during chronic stress are not well understood.…”

Section: Introductionmentioning

confidence: 99%

Chronic Stress Contributes to Cognitive Dysfunction and Hippocampal Metabolic Abnormalities in APP/PS1 Mice

Han

Wang

Geng³

et al. 2017

Cell Physiol Biochem

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Background/Aims: Stress response is determined by the brain, and the brain is a sensitive target for stress. Our previous experiments have confirmed that once the stress response is beyond the tolerable limit of the brain, particularly that of the hippocampus, it will have deleterious effects on hippocampal structure and function; however, the metabolic mechanisms for this are not well understood. Methods: Here, we used morris water maze, elisa and gas chromatography-time of flight/mass spectrometry to observe the changes in cognition, neuropathology and metabolomics in the hippocampus of APP/PS1 mice and wild-type (C57) mice caused by chronic unpredictable mild stress (CUMS), we also further explored the correlation between cognition and metabolomics. Results: We found that 4 weeks of CUMS aggravated cognitive impairment and increased amyloid-β deposition in APP/PS1 mice, but did not affect C57 mice. Under non-stress conditions, compared with C57 mice, there were 8 different metabolites in APP/PS1 mice. However, following CUMS, 3 different metabolites were changed compared with untreated C57 mice. Compared to APP/PS1 mice, there were 7 different metabolites in APP/PS1+CUMS mice. Among these alterations, 3-hydroxybutyric acid, valine, serine, beta-alanine and o-phosphorylethanolamine, which are involved in sphingolipid metabolism, synthesis and degradation of ketone bodies, and amino acid metabolism. Conclusion: The results indicate that APP/PS1 mice are more vulnerable to stress than C57 mice, and the metabolic mechanisms of stress-related cognitive impairment in APP/PS1 mice are related to multiple pathways and networks, including sphingolipid metabolism, synthesis and degradation of ketone bodies, and amino acid metabolism.

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“…The MWM test was performed to evaluate the escape latency (the time to reach the hidden platform), travelled distance (the length of swim path) and time across the platform, as described in previous studies [19, 20]. Recognition tasks were performed as described previously [21].…”

Section: Methodsmentioning

confidence: 99%

TRPML1 Participates in the Progression of Alzheimer’s Disease by Regulating the PPARγ/AMPK/Mtor Signalling Pathway

Zhang

Fang

Chen

et al. 2017

Cell Physiol Biochem

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Background: TRPML1 is reported to be involved in the pathogenesis of Alzheimer’s disease (AD) by regulating autophagy; however, the underlying mechanism is not completely clear. Methods: We developed an APP/PS1 transgenic animal model that presents with AD. TRPML1 was also overexpressed in these mice. Protein expression levels were determined by Western blot. Morris water maze (MWM) and recognition tasks were performed to characterize cognitive ability. TUNEL assays were analysed for the detection of neuronal apoptosis. Primary neurons were isolated and treated with the vehicle, Aβ1-42 or Aβ1-42 + mTOR activator, as well as infected with the recombinant adenovirus TRPML1 overexpression vector in vitro. Cell viability was measured by the MTS assay, and lysosomal Ca²⁺ was also measured. Results: In the APP/PS1 transgenic mice, TRPML1 was downregulated, the PPARγ/AMPK signalling pathway was activated, the mTOR/S6K signalling pathway was suppressed, and autophagic lysosome reformation (ALR)-related proteins were upregulated. TRPML1 overexpression or treatment with PPARγ and AMPK inhibitors or an mTOR activator reduced the expression levels of ALR-related proteins, rescued the memory and recognition impairments and attenuated neuronal apoptosis in mice with the APP/PS1 transgenes. In vitro experiments showed that TRPML1 overexpression or treatment with the mTOR activator propranolol attenuated the Aβ1-42-suppressed cell viability and the Aβ1-42-decreased lysosomal [Ca²⁺] ion concentration in primary neurons. TRPML1 overexpression or treatment with the mTOR activator propranolol also attenuated the Aβ1-42-inhibited mTOR/S6K signalling pathway and the Aβ1-42-induced ALR-related protein expression levels. Conclusion: TRPML1 is involved in the pathogenesis of AD by regulating autophagy at least in part through the PPARγ/AMPK/mTOR signallingpathway.

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Effects of Chronic Stress on Cognition in Male SAMP8 Mice

Cited by 38 publications

References 55 publications

Changes in C57BL6 Mouse Hippocampal Transcriptome Induced by Hypergravity Mimic Acute Corticosterone-Induced Stress

Changes in C57BL6 Mouse Hippocampal Transcriptome Induced by Hypergravity Mimic Acute Corticosterone-Induced Stress

Chronic Stress Contributes to Cognitive Dysfunction and Hippocampal Metabolic Abnormalities in APP/PS1 Mice

TRPML1 Participates in the Progression of Alzheimer’s Disease by Regulating the PPARγ/AMPK/Mtor Signalling Pathway

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