Capsaicin Attenuates The Stress-induced Memory Deficits And Spine Loss

Alzheimer disease (AD) is one of the most common neurodegenerativediseases, it makes up approximately70%of all dementia cases. There exist two majordistinctive hallmark lesions in the AD brain, which are neurofibrillary tanglescompsed of hyperphosphorylated microtuble-associated protein tau and senile plaquescoposed of β-amyloid. A large number of study have found a variety of animal modelsof stress, such as starvation and cold water stress can cause reversiblehyperphosphorylation of tau protein in cortex and hippocampus, may closely relatedto reduce the memory function. The hippocampus plays critical roles in certain typesof memory, including spatial memory, the underlying mechanisms are believed todepend on activity-dependent hippocampal synaptic plasticity, which occurs changesof LTP and LTD. Stress can reduce the number of dendritic spines and damage LTP.TRPV1is a member of a large family of calcium-permeable nonselective cationchannels, and is activated not only by capsaicin but also by heat, acid and variouslipids. Although TRPV1is known to be involved in peripheral nociception, it is alsowidely expressed in the hippocampus, cerebral cortex, cerebellum, mesencephalonand hypothalamus of the brain, suggesting that TRPV1plays a significant role in theCNS. It remains unclear whether the TRPV1channel antagonizes the effects of stresson hippocampal function.Objective: To explore the effects of capsaicin activate TRPV1on rat’s study andmemory ability and the underlying mechanisms.Materials and Methods: Two-month-old SD male rats90were randomly dividedinto control, stress and capsaicin+stress. After Capsaicin fed for half an hour, the ratsput into0℃cold water for5min.Behavior of rats were detected by morris watermaze, phosphorylation of tau protein and its associated kinase and phosphatase levelsof protein expression were tested with immuohistochemistry and Western blotting in rat brain, neuronal morphology and number of dendritic spines were observated byGolgi staining.Results: Compared with the control group the Morris water maze latency wassignificantly longer in stress of group, and relative to shorten in capscaincin+stressgroup. Stress group’s tau protein phosphorylation levels were significantly higher thancontrol group, capsaincin+stress group the levels of tau phosphorylation werereversed, and associated with PP2Ac activity increased. Golgi staining found thestress group show the neuronal dendritic branching and dendritic spine densityreduced, capsaincin+stress group show the neuronal morphology and number ofdendritic spines return to normal.Conclusion: Capsaicin activates TRPV1receptors reduces tau phosphorylation, andprevents the stress induced spine loss and restores memory deficits...