title: Environmental enrichment increases the GFAP+ stem cell pool and reverses hypoxia-induced cognitive deficits in juvenile mice.
abstract: Premature children born with very low birth weight (VLBW) can suffer chronic hypoxic injury as a consequence of abnormal lung development and cardiovascular abnormalities, often leading to grave neurological and behavioral consequences. Emerging evidence suggests that environmental enrichment improves outcome in animal models of adult brain injury and disease; however, little is known about the impact of environmental enrichment following developmental brain injury. Intriguingly, data on socio-demographic factors from longitudinal studies that examined a number of VLBW cohorts suggest that early environment has a substantial impact on neurological and behavioral outcomes. In the current study, we demonstrate that environmental enrichment significantly enhances behavioral and neurobiological recovery from perinatal hypoxic injury. Using a genetic fate-mapping model that allows us to trace the progeny of GFAP+ astroglial cells, we show that hypoxic injury increases the proportion of astroglial cells that attain a neuronal fate. In contrast, environmental enrichment increases the stem cell pool, both through increased stem cell proliferation and stem cell survival. In mice subjected to hypoxia and subsequent enrichment there is an additive effect of both conditions on hippocampal neurogenesis from astroglia, resulting in a robust increase in the number of neurons arising from GFAP+ cells by the time these mice reach full adulthood.
authors: Child Study Center, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
authors: Natalina
authors: N
authors: Salmaso
authors: John
authors: J
authors: Silbereis
authors: Mila
authors: M
authors: Komitova
authors: Patrick
authors: P
authors: Mitchell
authors: Katherine
authors: K
authors: Chapman
authors: Laura R
authors: LR
authors: Ment
authors: Michael L
authors: ML
authors: Schwartz
authors: Flora M
authors: FM
authors: Vaccarino
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D003072:Cognition Disorders / Q000209:etiology / Q000451:nursing* / Q000473:pathology*; D003857:Deoxyuridine / Q000378:metabolism; D004195:Disease Models, Animal; D004777:Environment; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000150:complications; D007065:Idoxuridine / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism; D055495:Neurogenesis; D009457:Neuroglia / Q000378:metabolism; D011960:Receptors, Estrogen / Q000235:genetics; D013234:Stem Cells / Q000378:metabolism / Q000502:physiology*; D013629:Tamoxifen / Q000494:pharmacology
chemical_list: D004965:Estrogen Antagonists; D005904:Glial Fibrillary Acidic Protein; D019394:Ki-67 Antigen; D009419:Nerve Tissue Proteins; D011960:Receptors, Estrogen; C485184:enhanced green fluorescent protein; D013629:Tamoxifen; D049452:Green Fluorescent Proteins; D001973:Bromodeoxyuridine; D007065:Idoxuridine; D003857:Deoxyuridine