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The Journal of Neuroscience, March 17, 2004, 24(11):2832-2836; doi:10.1523/JNEUROSCI.0110-04.2004

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Neural Stem Cells Show Bidirectional Experience-Dependent Plasticity in the Perinatal Mammalian Brain

Tod E. Kippin,^1 * Sean W. Cain,^2 * Zahra Masum,² and Martin R. Ralph²

Departments of ¹Medical Genetics and Microbiology and ²Psychology, University of Toronto, Toronto, Ontario M5S 1A8, Canada

Many of the effects of prenatal stress on the endocrine function, brain morphology, and behavior in mammals can be reversed by brief sessions of postnatal separation and handling. We have tested the hypothesis that the effects of both the prenatal and postnatal experiences are mediated by negative and positive regulation of neural stem cell (NSC) number during critical stages in neurodevelopment. We used thein vitroclonal neurosphere assay to quantify NSCs in hamsters that had experienced prenatal stress (maternal restraint stress for 2 hr per day, for the last 7 d of gestation), postnatal handling (maternal–offspring separation for 15 min per day during postnatal days 1–21), orboth. Prenatal stress reduced the number of NSCs derived from the subependyma of the lateral ventricle. The effect was already present at postnatal day 1 and persisted into adulthood (at least 14 months of age). Similarly, prenatal stress reduced in vivo proliferation in the adult subependyma of the lateral ventricle. Conversely, postnatal handling increased NSC number and reversed the effect of prenatal stress. The effects of prenatal stress on NSCs and proliferation and the effect of postnatal handling on NSCs did not differ between male and females. The findings demonstrate that environmental factors can produce changes in NSC number that are present at birth and endure into late adulthood. These changes may underlie some of the behavioral effects produced by prenatal stress and postnatal handling.

Key words: prenatal stress; postnatal handling; maternal separation; neurodevelopment; neurosphere; neurons; glia

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Received Sep 5, 2003; revised February 4, 2004; accepted February 7, 2004.

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