Differential stroke-induced proliferative response of distinct precursor cell subpopulations in the young and aged dentate gyrus

• Published in: Neuroscience Vol. 169; no. 3; pp. 1279 - 1286
• Main Authors: Walter, J, Keiner, S, Witte, O.W, Redecker, C
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 01-09-2010; Elsevier
• Subjects: Aging; Aging - pathology; Animals; Biological and medical sciences; Cell Proliferation; Cell Survival; Cerebral Infarction - pathology; Dentate Gyrus - pathology; endogenous stem cells; focal ischemia; Fundamental and applied biological sciences. Psychology; Genes, Reporter; Green Fluorescent Proteins - genetics; Intermediate Filament Proteins - genetics; Male; Medical sciences; Mice; Mice, Transgenic; Nerve Tissue Proteins - genetics; Nestin; Neural Stem Cells - pathology; Neurogenesis; Neuroglia - pathology; Neurology; Neurons - pathology; proliferation; Stroke - pathology; Vascular diseases and vascular malformations of the nervous system; Vertebrates: nervous system and sense organs; doublecortin; DG; nestin; SGZ; phosphate-buffered saline; GFP; neuronal nuclei; neurogenesis; focal ischemia; PBS; endogenous stem cells; proliferation; TBS; granule cell layer; subgranular zone; GFAP; GCL; dentate gyrus; NeuN; bromodeoxyuridine; DCX; tris-buffered saline; green-fluorescent protein; aging; glial fibrillary acidic protein; BrdU; Cell proliferation; Nervous system diseases; Stroke; Senescence; Stem cell; Central nervous system; Precursor cell; Cardiovascular disease; Neurogenesis; Encephalon; Cerebral disorder; Vascular disease; Dentate gyrus; Central nervous system disease; Hippocampus; Cerebrovascular disease
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2010.05.035

Abstract The capability of the adult brain to generate new hippocampal neurons after brain insults like stroke is decreasing during the aging process. Recent evidence further indicates that the proliferative properties of the precursor cells change in the aged brain. We therefore analyzed the early proliferative response of distinct precursor cell populations in the subgranular zone of the dentate gyrus in 3 and 16 months old transgenic nestin-green-fluorescent protein mice 4 days after ischemic cortical infarcts. A detailed immunocytochemical analysis of proliferating precursors revealed a significant infarct-induced activation of the earliest radial glia-like precursor cells (type 1 cells) and the more differentiated precursor cell subtypes (type 2b cells) in young mice. In contrast the proliferation of early neuronal precursor cells (type 2a cells) was stimulated in the aged brain. Additional long-term experiments further demonstrated that this differential proliferative response of distinct precursor cells is associated with an enhanced number of newborn neurons in the young DG after stroke whereas this increase in neurogenesis was absent in the aged brain. However, our study demonstrates that even precursor cells in the aged hippocampus possess the ability to respond to remote cortical infarcts.