Temporal profile of subventricular zone progenitor cell migration following quinolinic acid-induced striatal cell loss.
A number of studies have demonstrated directed migration of neural progenitor cells to sites of brain injury and disease, however a detailed examination of when a cell is "born" in relation to injury induction and the migratory response of that cell has not previously been determined. This study therefore examined the temporal correlation between progenitor cell proliferation ("birth") and neuroblast migratory response into the damaged striatum following quinolinic acid (QA) lesioning of the adult rat striatum. Retroviral labeling of subventricular zone (SVZ)-derived progenitor cells demonstrated that cell loss in the QA-lesioned striatum increased progenitor cell migration through the rostral migratory stream (RMS) for up to 30 days. In addition, a population of dividing cells originating from the SVZ generated doublecortin positive neuroblasts that migrated into the damaged striatum in response to cell loss invoked by the QA lesion. Quantification of bromodeoxyuridine (BrdU)-labeled cells co-expressing doublecortin revealed that the majority of cells present in the damaged striatum were generated from progenitor cells dividing within 2 days either prior to or following the QA lesion. In contrast, cells dividing 2 or more days following QA lesioning, migrated into the striatum and exhibited a glial phenotype. These results demonstrate that directed migration of SVZ-derived cells and neuroblast differentiation in response to QA lesioning of the striatum is acute and transient. We propose this is predominantly due to a reduced capacity over time for newly generated neuroblasts to respond to the lesioned environment due to a loss or inhibition of migratory cues.
Gordon
R J
RJ
Department of Pharmacology and Clinical Pharmacology, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand.
Tattersfield
A S
AS
Vazey
E M
EM
Kells
A P
AP
McGregor
A L
AL
Hughes
S M
SM
Connor
B
B
D053687:Adult Stem Cells / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation; D002552:Cerebral Ventricles / Q000166:cytology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000293:injuries; D000089662:Doublecortin Protein; D005822:Genetic Vectors / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000096:biosynthesis; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D017378:Quinolinic Acid / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D009419:Nerve Tissue Proteins; D049452:Green Fluorescent Proteins; D017378:Quinolinic Acid; D001973:Bromodeoxyuridine