Abstract  Alzheimer's disease (AD) is a neurodegenerative disorder that causes progressive memory and cognitive impairment with gender difference in specific cognitive ability domains, pathology, and risk of AD. Since valproic acid (VPA) is a widely used mood stabilizer and an antiepileptic drug, which exhibits multiple neuroprotective activities on AD, this study intended to investigate the gender difference in the effect of VPA on APP/PS1 double transgenic mice modeling AD. Behavioral experiments showed that VPA reduced the autonomous behaviors, improved learning and memory, and exhibited gender differences in AD mice compared with the control mice. The decrease in senile plaque, amyloid �� (A��) 40, and A��42 caused by VPA in the male AD mice was more notable than that in the female AD mice. Meanwhile, VPA protected brain cells from dying notably in the male AD mice but only slightly in the female AD mice, and VPA treatment thickened the postsynaptic density and markedly increased the number and density of presynaptic vesicles in both male and female AD mice. However, the effects of rescuing early synaptic structural and functional deficits by VPA were more obvious in the male mice. Overall, these results supported the hypothesis that gender difference significantly influences AD and indicated that VPA may be a promising remedy for AD if basic biological differences and gender specificity were prudently taken into account.

Keywords   Alzheimer's disease; gender difference; valproic acid; cognitive improvement senile plaque

Received   2016-4-8����
Accepted  2016-7-27

Funding  This work was supported by the grants from the National Natural Science Foundation of China (Nos. 81371221 and 30970986), Program for New Century Excellent Talents in University (No. NCET-11-1084), Chongqing Education Commission Science and Technology Res

* Correspondence address  Tel: +86-23-68485763; Fax: +86-23-89129930; E-mail: [email protected]

    Password Help