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.
Background: Repetitive transcranial magnetic stimulation (rTMS) has been used to improve cognitive function, but the stimulation protocols are variable and the underlying mechanism is unclear. Therefore, we intend to examine whether 5Hz rTMS with 30% maximum output could improve cognitive functions in senescence-accelerated-prone mouse 8 (SAMP8) through changing synaptic plasticity. Methods: SAMP8 and senescence-accelerated-prone mouse/resistant 1 (SAMR1) (7-month old male) were randomly divided into 3 groups: SMAP8 rTMS group (P8-rTMS), SMAP8 sham-rTMS group (P8-sham), and SAMR1 sham-rTMS group (R1-sham). The P8-rTMS group was treated daily with 5Hz rTMS with 30% maximum output for 14 consecutive days, whereas the other two groups were controls without rTMS stimulation. Morris water maze (MWM) experiment was performed after rTMS or sham treatment to assess the effect of rTMS on cognitive function. Reverse transcription polymerase chain reaction and Western blot assays were used to detect the mRNA and protein expression of presynaptic Synapsin (SYN) and postsynaptic density 95 (PSD95) in the hippocampus of these mice. Results: The mean escape latency of the P8-rTMS group was significantly shorter than that of the P8-sham group. The number of platform crossings of the P8-rTMS group was significantly higher than that of the P8-sham group. rTMS significantly upregulated the protein and mRNA expression of SYN and PSD95 in the hippocampus of p8-rTMS mice compared to those of P8 sham mice. Conclusion: 5Hz rTMS with 30% maximum output enhances learning and memory in the SAMP8 mice. This improvement may be associated with the increased expression of synaptic structure proteins SYN and PSD95 in the hippocampus.
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