[Abstract Title]. - Society for Neuroscience

Poster
229. Neuronal and Glial Proliferation III
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 229.5/A5
Topic: A.02.a. Proliferation
Title: The histon deacetylase inhibitor, sodium butyrate, stimulates cell proliferation in the
ischemic brain: roles of BDNF-TrkB signaling
Authors: *H. KIM, P. R. LEEDS, D.-M. CHUANG;
Mol. Neurobiol Section, Natl. Inst. Mental Health/NIH, Bethesda, MD
Abstract: Neurogenesis occurs in the rostral subventricular zone (SVZ) and hippocampal
dentate gyrus (DG) in the adult brain. It is known that cerebral ischemia enhances neurogenesis
in the ischemic brain of rodents. The present study investigated whether the beneficial effects of
sodium butyrate (SB), an HDAC inhibitor, are associated with an enhancement of cell
proliferation in the ischemic brain. Rats were subjected to permernant middle cerebral artery
occlusion (pMCAO) followed by daily injections with SB (300 mg/kg, i.p.). Bromo-2'
deoxyuridine (BrdU) was also given by injections (50 mg/kg, i.p.) after ischemia to label
newborn cells. We confirmed that SB treatment markedly stimulated BrdU labeling in the SVZ,
hippocampal DG and frontal cortex of the ischemic brain. SB treatment further increased the
number of cells expressing doublecortin, nestin, GFAP, phospho-CREB and brain derived
neurotrophic factor (BDNF) in various regions at 7 and 14 days after pMCAO. SB treatment also
markedly increased the levels of acetylated histone H3 in cells expressing NeuN in the ischemic
brain. Intraventricular injection of K252a, a TrkB receptor antagonist, markedly reduced SBinduced
cell proliferation in the SVZ and DG, and blocked the drug-induced behavioral benefits,
suggesting the involvement of BDNF-TrkB signaling in the enhanced proliferation. HDAC
inhibitor-induced cell proliferation may contribute to the drug‟s long-term beneficial effects after
ischemic injury. Given that there is no effective treatment for stroke, HDAC inhibitors such as
SB should be evaluated for their potential use for clinical trials in stroke patients.
Disclosures: H. Kim, None; P.R. Leeds, None; D. Chuang, None.
Poster
229. Neuronal and Glial Proliferation III