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CLC number: R338.64

On-line Access: 2019-03-01

Received: 2018-06-19

Revision Accepted: 2018-10-04

Crosschecked: 2019-01-10

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Citations:  Bibtex RefMan EndNote GB/T7714


Jariya Umka Welbat


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Journal of Zhejiang University SCIENCE B 2019 Vol.20 No.3 P.253-263


Valproic acid withdrawal ameliorates impairments of hippocampal-spatial working memory and neurogenesis

Author(s):  Wanassanun Pannangrong, Apiwat Sirichoat, Trai Wongsiri, Peter Wigmore, Jariya Umka Welbat

Affiliation(s):  Department of Anatomy, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand; more

Corresponding email(s):   jariya@kku.ac.th

Key Words:  Hippocampus, Neurogenesis, Spatial memory, Valproic acid

Wanassanun Pannangrong, Apiwat Sirichoat, Trai Wongsiri, Peter Wigmore, Jariya Umka Welbat. Valproic acid withdrawal ameliorates impairments of hippocampal-spatial working memory and neurogenesis[J]. Journal of Zhejiang University Science B, 2019, 20(3): 253-263.

@article{title="Valproic acid withdrawal ameliorates impairments of hippocampal-spatial working memory and neurogenesis",
author="Wanassanun Pannangrong, Apiwat Sirichoat, Trai Wongsiri, Peter Wigmore, Jariya Umka Welbat",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Valproic acid withdrawal ameliorates impairments of hippocampal-spatial working memory and neurogenesis
%A Wanassanun Pannangrong
%A Apiwat Sirichoat
%A Trai Wongsiri
%A Peter Wigmore
%A Jariya Umka Welbat
%J Journal of Zhejiang University SCIENCE B
%V 20
%N 3
%P 253-263
%@ 1673-1581
%D 2019
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1800340

T1 - Valproic acid withdrawal ameliorates impairments of hippocampal-spatial working memory and neurogenesis
A1 - Wanassanun Pannangrong
A1 - Apiwat Sirichoat
A1 - Trai Wongsiri
A1 - Peter Wigmore
A1 - Jariya Umka Welbat
J0 - Journal of Zhejiang University Science B
VL - 20
IS - 3
SP - 253
EP - 263
%@ 1673-1581
Y1 - 2019
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1800340

valproic acid (VPA), an agent that is used to treat epileptic seizures, can cause spatial memory impairment in adults and children. This effect is thought to be due to the ability of VPA to inhibit neurogenesis in the hippocampus, which is required for learning. We have previously used an animal model to show that VPA significantly impairs hippocampal-spatial working memory and inhibits neuronal generation in the sub-granular zone of the dentate gyrus. As there are patient reports of improvements in memory after discontinuing VPA treatment, the present study investigated the recovery of both spatial memory and hippocampal neurogenesis at two time points after withdrawal of VPA. Male Wistar rats were given intraperitoneal injections of 0.9% normal saline or VPA (300 mg/kg) twice a day for 10 d. At 1, 30, or 45 d after the drug treatment, the novel object location (NOL) test was used to examine spatial memory; hippocampal cell division was counted using Ki67 immunohistochemistry, and levels of brain-derived neurotrophic factor (BDNF) and Notch1 were measured using western immunoblotting. Spatial working memory was impaired 1 and 30 d after the final administration, but was restored to control levels by 45 d. Cell proliferation had increased to control levels at 30 and 45 d. Both markers of neurogenesis (BDNF and Notch1 levels) had returned to control levels at 45 d. These results demonstrate that memory recovery occurs over a period of six weeks after discontinuing VPA treatment and is preceded by a return of hippocampal neurogenesis to control levels.


方法:雄性Wistar大鼠每天两次腹膜内注射0.9%生理盐水或丙戊酸(300 mg/kg),持续10天.在药物治疗结束后第1、30或45天,使用新物体位置(NOL)测试来检查空间记忆;使用Ki67免疫组织化学计数海马细胞分裂情况;并使用免疫印迹法(western immunoblotting)测量脑源性神经营养因子(BDNF)和Notch1的水平.


Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


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