title: Substantial migration of SVZ cells to the cortex results in the generation of new neurons in the excitotoxically damaged immature rat brain.
abstract: Mammalian SVZ progenitors continuously generate new neurons in the olfactory bulb. After injury, changes in SVZ cell number suggest injury-induced migration. Studies that trace the migration of SVZ precursors into neurodegenerating areas are lacking. Previously, we showed a decrease in BrdU+SVZ cells following excitotoxic damage to the immature rat cortex. Here, we demonstrate that NMDA-induced injury forces endogenous Cell Tracker Green (CTG) labeled VZ/SVZ precursors out of the SVZ into the neurodegenerating cortex. CTG+/Nestin+/Filamin A+ precursors are closely associated with vimentin+/GFAP+/GLAST+ filaments and express both chemokine receptor CXCR4 and Robo1. In the cortex, SVZ-derived progenitors show a progressive expression of developing, migrating and mature neurons and glial markers. CTG+/GFAP+ astrocytes greatly outnumber CTG+/MAP2+/NeuN+ neurons. SVZ-derived progenitors differentiate into both tbr1+ cortical glutamatergic neurons and calretinin+ interneurons. But, there is little integration of these neurons into the existing circuitry, as seen by Fluorogold retrograde tracing from the internal capsule.
authors.affiliation: Medical Histology, Department of Cell Biology, Physiology and Immunology, Neuroscience Institute, Autonomous University of Barcelona, Spain. maryam.faiz@neuro.gu.se
authors.forename: Maryam
authors.initials: M
authors.lastname: Faiz
authors.forename: Laia
authors.initials: L
authors.lastname: Acarin
authors.forename: Sonia
authors.initials: S
authors.lastname: Villapol
authors.forename: Stefan
authors.initials: S
authors.lastname: Schulz
authors.forename: Bernardo
authors.initials: B
authors.lastname: Castellano
authors.forename: Berta
authors.initials: B
authors.lastname: Gonzalez
mesh_terms: D000367:Age Factors; D000818:Animals; D001253:Astrocytes / Q000166:cytology; D015415:Biomarkers / Q000378:metabolism; D064032:Calbindin 2; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D005260:Female; D005911:Gliosis / Q000473:pathology; D020772:Internal Capsule / Q000166:cytology / Q000254:growth & development; D008297:Male; D009044:Motor Cortex / Q000473:pathology* / Q000502:physiology; D016202:N-Methylaspartate / Q000633:toxicity; D009410:Nerve Degeneration / Q000473:pathology* / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology; D009498:Neurotoxins / Q000633:toxicity; D051381:Rats; D020318:Rats, Long-Evans; D019718:Receptors, CXCR4 / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D013003:Somatosensory Cortex / Q000473:pathology* / Q000502:physiology; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D000097905:Roundabout Proteins
chemical_list: D015415:Biomarkers; D064032:Calbindin 2; D018690:Excitatory Amino Acid Agonists; D016202:N-Methylaspartate; D009419:Nerve Tissue Proteins; D009498:Neurotoxins; D019718:Receptors, CXCR4; D011971:Receptors, Immunologic; D064030:S100 Calcium Binding Protein G; D000097905:Roundabout Proteins; C576512:Calb2 protein, rat; C486264:Cxcr4 protein, rat