title: Reelin-deficient mice show impaired neurogenesis and increased stroke size.
abstract: Reelin (Reln) is a protein involved in migration of newborn neurons during development. Reln mutations produce the reeler phenotype in mice, which is characterized by a defect in brain lamination, and autosomal recessive lissencephaly in humans. Reln expression persists in adult brain, but little is known about its function. We used reeler mice to investigate the effects of Reln deficiency on neurogenesis and the response to injury in the adult brain. Newborn neurons were decreased in number in the dentate gyrus and rostral migratory stream of reeler, compared to wild-type, mice. This was due, at least in part, to impaired cell migration. In addition, reeler mice showed increased susceptibility to ischemic brain injury. Cerebral infarcts from middle cerebral artery occlusion were larger in reeler than in wild-type mice, and associated neurobehavioral abnormalities were more severe. The brains of reeler mice also showed larger excitotoxic lesions after the intracerebral injection of N-methyl-D-aspartate. Finally, despite the fact that reeler mice had larger cerebral infarcts, the ischemia-induced enhancement of neurogenesis observed in wild-type mice was attenuated. These findings suggest that, in addition to its neurodevelopmental effects, Reln deficiency continues to influence neurogenesis and ischemic neuronal injury in the adult brain.
authors.affiliation: Buck Institute for Age Research, 8001 Redwood Blvd., Novato, CA 94945, USA.
authors.forename: Seok Joon
authors.initials: SJ
authors.lastname: Won
authors.forename: Sun Hee
authors.initials: SH
authors.lastname: Kim
authors.forename: Lin
authors.initials: L
authors.lastname: Xie
authors.forename: Yaoming
authors.initials: Y
authors.lastname: Wang
authors.forename: Xiao Ou
authors.initials: XO
authors.lastname: Mao
authors.forename: Kunlin
authors.initials: K
authors.lastname: Jin
authors.forename: David A
authors.initials: DA
authors.lastname: Greenberg
mesh_terms: D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D064026:Calbindins; D015816:Cell Adhesion Molecules, Neuronal / Q000172:deficiency* / Q000502:physiology*; D002452:Cell Count / Q000379:methods; D002544:Cerebral Infarction / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D000089622:Doublecortin Domain Proteins; D016326:Extracellular Matrix Proteins / Q000172:deficiency* / Q000502:physiology*; D015870:Gene Expression / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000502:physiology*; D009474:Neurons / Q000473:pathology / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism; D000091042:Reelin Protein; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D012697:Serine Endopeptidases / Q000172:deficiency* / Q000502:physiology*; D020521:Stroke / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D064026:Calbindins; D015816:Cell Adhesion Molecules, Neuronal; D000089622:Doublecortin Domain Proteins; D016326:Extracellular Matrix Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D000091042:Reelin Protein; D064030:S100 Calcium Binding Protein G; C000717127:RELN protein, human; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases; D001973:Bromodeoxyuridine