Gene profiles and electrophysiology of doublecortin-expressing cells in the subventricular zone after ischemic stroke.
Stroke increases neuroblasts in the subventricular zone (SVZ) of the lateral ventricle and these neuroblasts migrate toward the ischemic boundary to replace damaged neurons. Using brain slices from the nonischemic adult rat and transgenic mice that expressed enhanced green fluorescent protein (EGFP) concomitantly with doublecortin (DCX), a marker for migrating neuroblasts, we recorded electrophysiological characteristics while simultaneously analyzing the gene expression in single SVZ cells. We found that SVZ cells expressing the DCX gene from the nonischemic rat had a mean resting membrane potential (RMP) of -30 mV. DCX-EGFP-positive cells in the nonischemic SVZ of the transgenic mouse had a mean RMP of -25+/-7 mV and did not exhibit Na(+) currents, characteristic of immature neurons. However, DCX-EGFP-positive cells in the ischemic SVZ exhibited a hyperpolarized mean RMP of -54+/-18 mV and displayed Na(+) currents, indicative of more mature neurons. Single-cell multiplex RT-PCR analysis revealed that DCX-EGFP-positive cells in the nonischemic SVZ of the transgenic mouse expressed high neural progenitor marker genes, Sox2 and nestin, but not mature neuronal marker genes. In contrast, DCX-EGFP-positive cells in the ischemic SVZ expressed tyrosine hydroxylase, a mature neuronal marker gene. Together, these data indicate that stroke changes gene profiles and the electrophysiology of migrating neuroblasts.
Department of Neurology, Henry Ford Hospital, Detroit, Michigan 48202, USA.
Xian Shuang
XS
Liu
Michael
M
Chopp
Xue Guo
XG
Zhang
Rui Lan
RL
Zhang
Ben
B
Buller
Ann
A
Hozeska-Solgot
Sara R
SR
Gregg
Zheng Gang
ZG
Zhang
D000818:Animals; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D004594:Electrophysiology; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000235:genetics*; D008297:Male; D008564:Membrane Potentials; D051379:Mice; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D020521:Stroke / Q000235:genetics / Q000378:metabolism*
C000714847:Dcx protein, mouse; C000714848:Dcx protein, rat; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides