Valproic acid alleviates memory deficits and attenuates amyloid-β deposition in transgenic mouse model of Alzheimer's disease.
In the brains of patients with Alzheimer's disease (AD) and transgenic AD mouse models, astrocytes and microglia activated by amyloid-β (Aβ) contribute to the inflammatory process that develops around injury in the brain. Valproic acid (VPA) has been shown to have anti-inflammatory function. The present study intended to explore the therapeutic effect of VPA on the neuropathology and memory deficits in APPswe/PS1ΔE9 (APP/PS1) transgenic mice. Here, we report that VPA-treated APP/PS1 mice markedly improved memory deficits and decreased Aβ deposition compared with the vehicle-treated APP/PS1 mice. Moreover, the extensive astrogliosis and microgliosis as well as the increased expression in interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the hippocampus and cortex of APP/PS1 transgenic mice were significantly reduced following administration of VPA, which attenuated neuronal degeneration. Concomitantly, VPA alleviated the levels of p65 NF-κB phosphorylation and enhanced the levels of acetyl-H3, Bcl-2, and phospho-glycogen synthase kinase (GSK)-3β that occurred in the hippocampus of APP/PS1 transgenic mice. These results demonstrate that VPA could significantly ameliorate spatial memory impairment and Aβ deposition at least in part via the inhibition of inflammation, suggesting that administration of VPA could provide a therapeutic approach for AD.
Department of Anatomy, Guangzhou Medical University, Guangzhou, 510182, Guangdong, China, xag2005@sohu.com.
Ai-Guo
AG
Xuan
Xue-Bing
XB
Pan
Peng
P
Wei
Wei-Dong
WD
Ji
Wen-Juan
WJ
Zhang
Ji-Hong
JH
Liu
Le-Peng
LP
Hong
Wen-Liang
WL
Chen
Da-Hong
DH
Long
D000544:Alzheimer Disease / Q000150:complications* / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008569:Memory Disorders / Q000150:complications* / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008822:Mice, Transgenic; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D053764:Presenilin-1 / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D065853:Spatial Learning / Q000187:drug effects; D014635:Valproic Acid / Q000494:pharmacology / Q000627:therapeutic use*
D016229:Amyloid beta-Peptides; D016207:Cytokines; D006657:Histones; D053764:Presenilin-1; D012333:RNA, Messenger; D014635:Valproic Acid