Quantitative analysis of the generation of different striatal neuronal subtypes in the adult brain following excitotoxic injury.
Recent findings in adult rodents have provided evidence for the formation of new striatal neurons from subventricular zone (SVZ) precursors following stroke. Little is known about which factors determine the magnitude of striatal neurogenesis in the damaged brain. Here we studied striatal neurogenesis following an excitotoxic lesion to the adult rat striatum induced by intrastriatal quinolinic acid (QA) infusion. New cells were labeled with the thymidine-analogue 5-bromo-2'-deoxyuridine (BrdU) and their identity was determined immunocytochemically with various phenotypic markers. The unilateral lesion gave rise to increased cell proliferation mainly in the ipsilateral SVZ. At 2 weeks following the insult, there was a pronounced increase of the number of new neurons co-expressing BrdU and a marker of migrating neuroblasts, doublecortin, in the ipsilateral striatum, particularly its non-damaged medial parts. About 80% of the new neurons survived up to 6 weeks, when they expressed the mature neuronal marker NeuN and were preferentially located in the outer parts of the damaged area. Lesion-generated neurons expressed phenotypic markers of striatal medium spiny neurons (DARPP-32) and interneurons (parvalbumin or neuropeptide Y). The magnitude of neurogenesis correlated to the size of the striatal damage. Our data show for the first time that an excitotoxic lesion to the striatum can trigger the formation of new striatal neurons with phenotypes of both projection neurons and interneurons.
Collin
Tove
T
Laboratory of Neurogenesis and Cell Therapy, Section of Restorative Neurology, Wallenberg Neuroscience Center, BMC A11, SE-221 84 Lund, Sweden.
Arvidsson
Andreas
A
Kokaia
Zaal
Z
Lindvall
Olle
O
D000704:Analysis of Variance; D000818:Animals; D001930:Brain Injuries / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D049109:Cell Proliferation; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003342:Corpus Striatum / Q000473:pathology*; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D007839:Functional Laterality; D007150:Immunohistochemistry / Q000379:methods; D016014:Linear Models; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009416:Nerve Regeneration / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000145:classification / Q000473:pathology*; D009478:Neuropeptide Y / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D010320:Parvalbumins / Q000378:metabolism; D010641:Phenotype; D010750:Phosphoproteins / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D017378:Quinolinic Acid; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
C000714848:Dcx protein, rat; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D009478:Neuropeptide Y; D009479:Neuropeptides; D010320:Parvalbumins; D010750:Phosphoproteins; D002795:Choline O-Acetyltransferase; D010751:Phosphopyruvate Hydratase; D017378:Quinolinic Acid; D001973:Bromodeoxyuridine