Divergence in Morris Water Maze-Based Cognitive Performance under Chronic Stress Is Associated with the Hippocampal Whole Transcriptomic Modification in Mice

Sialic acids are postulated to improve cognitive abilities. This study aimed to evaluate the effects of sialic acid on behavior when administered in a free form as N-acetylneuraminic acid (Neu5Ac) to pregnant mothers or rat pups. The experiment involved 40 male 21-day-old rat pups and 20 15-day-pregnant rats that were randomized into four Neu5Ac treated groups: 0 (control), or 10, 20, and 40 mg/kg. Morris water maze test and shuttle box test were performed on the rat pups and maternal Neu5Ac-supplemented offspring on day 100 to evaluate their cognitive performance. The Neu5Ac levels in the cerebral cortex and hippocampus were tested with high-performance liquid chromatography-fluorescence detection (HPLC-FLD). We found that the maternal Neu5Ac-supplemented offspring showed better cognitive performance, less escape latency in the Morris water maze test, and less electric shock time shuttle box test, compared with the untreated control. In the meantime, the Neu5Ac level in the cerebral cortex and hippocampus of the offspring was higher in the Neu5Ac treatment group than that in the untreated control group. However, no significant differences were observed between rat pups in the treated and the untreated control groups in terms of cognitive performance and Neu5Ac content in the cerebral cortex and hippocampus. Maternal Neu5Ac supplementation during pregnancy could effectively promote the brain Neu5Ac content of the offspring and enhance their cognitive performance, but Neu5Ac had no such effect on rat pups while directly supplemented with Neu5Ac.

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Effects of Chronic Stress on Cognition in Male SAMP8 Mice

Cellular Physiology and Biochemistry ◽

10.1159/000447816 ◽

2016 ◽

Vol 39 (3) ◽

pp. 1078-1086 ◽

Cited By ~ 20

Author(s):

Jinhua Wang ◽

Jie Yuan ◽

Jingjuan Pang ◽

Jiang Ma ◽

Bing Han ◽

...

Keyword(s):

Synaptic Plasticity ◽

Chronic Stress ◽

Morris Water Maze ◽

Water Maze ◽

Cognitive Deficit ◽

Brain Aging ◽

Mild Stress ◽

Samp8 Mice ◽

The Impact ◽

Senescence Accelerated Mouse

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.

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P.1.g.001 Enhancement of cognitive performance by gabapentin in Morris water maze, elevated plus maze and passive avoidance tasks in naive mice

European Neuropsychopharmacology ◽

10.1016/s0924-977x(11)70522-3 ◽

2011 ◽

Vol 21 ◽

pp. S329

Author(s):

I. Komsuoglu Celikyurt ◽

O. Mutlu ◽

G. Ulak ◽

F. Akar ◽

F. Erden

Keyword(s):

Passive Avoidance ◽

Cognitive Performance ◽

Morris Water Maze ◽

Water Maze ◽

Elevated Plus Maze ◽

Plus Maze

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Genes associated with cognitive performance in the Morris water maze: an RNA-seq study

Scientific Reports ◽

10.1038/s41598-020-78997-6 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Vasiliy V. Reshetnikov ◽

Polina E. Kisaretova ◽

Nikita I. Ershov ◽

Anastasia S. Shulyupova ◽

Dmitry Yu. Oshchepkov ◽

...

Keyword(s):

Cognitive Performance ◽

Morris Water Maze ◽

Ampa Receptor ◽

Water Maze ◽

Long Term Potentiation ◽

Rna Seq ◽

Glutamatergic Transmission ◽

Term Potentiation ◽

Alternatively Spliced

AbstractLearning and memory are among higher-order cognitive functions that are based on numerous molecular processes including changes in the expression of genes. To identify genes associated with learning and memory formation, here, we used the RNA-seq (high-throughput mRNA sequencing) technology to compare hippocampal transcriptomes between mice with high and low Morris water maze (MWM) cognitive performance. We identified 88 differentially expressed genes (DEGs) and 24 differentially alternatively spliced transcripts between the high- and low-MWM-performance mice. Although the sets of DEGs and differentially alternatively spliced transcripts did not overlap, both were found to be enriched with genes related to the same type of biological processes: trans-synaptic signaling, cognition, and glutamatergic transmission. These findings were supported by the results of weighted-gene co-expression network analysis (WGCNA) revealing the enrichment of MWM-cognitive-performance-correlating gene modules with very similar Gene Ontology terms. High-MWM-performance mice manifested mostly higher expression of the genes associated with glutamatergic transmission and long-term potentiation implementation, which are processes necessary for memory acquisition and consolidation. In this set, there were genes participating in the regulation of trans-synaptic signaling, primarily AMPA receptor signaling (Nrn1, Nptx1, Homer3, Prkce, Napa, Camk2b, Syt7, and Nrgn) and calcium turnover (Hpca, Caln1, Orai2, Cpne4, and Cpne9). In high-MWM-performance mice, we also demonstrated significant upregulation of the “flip” splice variant of Gria1 and Gria2 transcripts encoding subunits of AMPA receptor. Altogether, our data helped to identify specific genes in the hippocampus that are associated with learning and long-term memory. We hypothesized that the differences in MWM cognitive performance between the mouse groups are linked with increased long-term potentiation, which is mainly mediated by increased glutamatergic transmission, primarily AMPA receptor signaling.

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