Gender difference in valproic acid-induced neuroprotective effects on APP/PS1 double transgenic mice modeling Alzheimer's disease.
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 β (Aβ) 40, and Aβ42 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.
Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China Department of Anatomy, Chongqing Medical University, Chongqing 400016, China.
Zhimin
Z
Long
Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China.
Qinghua
Q
Zeng
Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China Department of Anatomy, Chongqing Medical University, Chongqing 400016, China.
Kejian
K
Wang
Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China.
Akhilesh
A
Sharma
Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China Department of Anatomy, Chongqing Medical University, Chongqing 400016, China guiqionghe@hotmail.com.
Guiqiong
G
He
D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D007150:Immunohistochemistry; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008568:Memory / Q000187:drug effects / Q000502:physiology; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission; D018696:Neuroprotective Agents / Q000494:pharmacology; D010446:Peptide Fragments / Q000378:metabolism; D053764:Presenilin-1 / Q000235:genetics* / Q000378:metabolism; D012737:Sex Factors; D013569:Synapses / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D014635:Valproic Acid / Q000494:pharmacology*
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D000927:Anticonvulsants; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D053764:Presenilin-1; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D014635:Valproic Acid
Alzheimer's disease; cognitive improvement; gender difference; senile plaque; valproic acid