Neuroscience 2005 Abstract
| Presentation Number: | 788.13 |
|---|---|
| Abstract Title: | Valproate-induced toxicity in immature rat brain. |
| Authors: |
Kanai, H.*1
; Sadamatsu, M.1
; Leeds, P.3
; Sawa, A.2
; Chuang, D. M-.3
1Dept. Psych., Shiga Univ. Med. Sci., Otsu, Japan 2MD, Seta-Tsukinoma cho, Otsu, Shiga, 520-2192, 3USA, Seta-Tsukinoma cho, Otsu, Shiga, 520-2192, |
| Primary Theme and Topics |
Disorders of the Nervous System - Neurotoxicity, Inflammation, and Neuroprotection -- Cell death mechanisms |
| Secondary Theme and Topics | Disorders of the Nervous System<br />- Developmental Disorders<br />-- Genetic |
| Session: |
788. Neurotoxicity: Apoptosis Poster |
| Presentation Time: | Tuesday, November 15, 2005 1:00 PM-2:00 PM |
| Location: | Washington Convention Center - Hall A-C, Board # TT45 |
| Keywords: | Apoptosis, Histone deacetylase, Cerebellum, rat |
Valproic acid (VPA) is an anticonvulsant and one of the primary drugs used to treat bipolar mood disorder. It is also known to have teratogenetic side effects and to cause fetal valproate syndrome. VPA was recently found to be a direct inhibitor of histone deacetylase (HDAC). The hyperacetylation of histone induced by HDAC inhibitors causes anti-proliferation, thereby possibly affect developmental processes of brains. We previously found that VPA had opposing actions on the viability of immature and mature cerebellar granule cells (CGCs)(Kanai H et al., SFN abstract, 2002). VPA induced neurotoxicity in CGC cultures 0-4 days after plating, but was neuroprotective against excitotoxicity after more than 7 days in vitro (Kanai H et al., Pharmacogenomics J, 2004). This neurotoxic effect of VPA was concentration-dependent and correlated inversely with the age of the cultures. In this study, we hypothesized that HDAC inhibition of VPA causes neurotoxic effects in immature brains, and therefore explored VPA-induced neuronal damages in the brains of rat pups. Our results showed that numerous TUNEL-positive cells were present in the extragranular cell layer of cerebellum but not in the intergranular cell layer 24 h after a single injection of VPA (400 mg/kg, i.p.). Thus, the results in our study are consistent with a pro-apoptotic effect of VPA, perhaps through HDAC inhibition as reported in cancer cells.
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2005 Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience, 2005. Online.
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