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Proc Natl Acad Sci U S A. 2005 May 31;102(22):8036-41. Epub 2005 May 23.

Replaceable neurons and neurodegenerative disease share depressed UCHL1 levels.

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  • 1Laboratory of Animal Behavior, The Rockefeller University, Box 137, 1230 York Avenue, New York, NY 10021, USA.


Might there be systematic differences in gene expression between neurons that undergo spontaneous replacement in the adult brain and those that do not? We first explored this possibility in the high vocal center (HVC) of male zebra finches by using a combination of neuronal tracers, laser capture microdissection, and RNA profiling. HVC has two kinds of projection neurons, one of which continues to be produced and replaced in adulthood. HVC neurons of the replaceable kind showed a consistent and robust underexpression of the deubiquitination gene ubiquitin carboxyl-terminal hydrolase (UCHL1) that is involved with protein degradation. Singing behavior, known to increase the survival of adult-born HVC neurons in birds, significantly up-regulated the levels of UCHL1 in the replaceable neurons but not in their equally active nonreplaceable counterparts. We then looked in the mouse brain and found relatively low UCHL1 expression in granule neurons of the hippocampus and olfactory bulb, two well characterized types of replaceable neurons in mammals. UCHL1 dysfunction has been associated with neurodegeneration in Parkinson's, Alzheimer's, and Huntington's disease patients. In all these instances, reduced UCHL1 function may jeopardize the survival of CNS neurons.

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