The Journal of Neuroscience, June 1, 2002, 22(11):4670-4674
bcl-2 Overexpression Eliminates
Deprivation-Induced Cell Death of Brainstem Auditory Neurons
Sam P.
Mostafapour,
N. Mae
del
Puerto, and
Edwin W
Rubel
Virginia Merrill Bloedel Hearing Research Center and Department of
Otolaryngology, Head and Neck Surgery, University of Washington,
Seattle, Washington 98195
Deprivation of afferent input in young animals results in
transneuronal degeneration of postsynaptic sensory neurons in a variety
of species and sensory pathways. Transneuronal degeneration is generally not seen in adult animals. The cellular and
molecular basis for this dramatic developmental change in
susceptibility is not understood. One possibility is that genes
involved in the apoptotic process are involved in determining cell
death or survival after afferent deprivation. To further investigate
this possibility, we performed unilateral cochlear ablation on
wild-type and bcl-2-overexpressing mice at a variety of
ages. In postnatal day 5 (P5) or P8 wild-type mice, cochlea removal
resulted in a 54% or 31% neuronal loss in the anteroventral cochlear
nucleus (AVCN), respectively. When the same manipulation is performed
on a P30 mouse, no loss of AVCN neurons occurs. This confirmed a rather
abrupt change in the sensitivity to disruption of afferent input, a
critical period. However, in littermates expressing
bcl-2 under a neuron-specific enolase promoter, no
significant loss of AVCN neurons was observed at any age after
unilateral cochlear ablation. Furthermore, wild-type mice demonstrate
rapid expression of activated caspase-3 in AVCN neurons within hours of
deafferentation, whereas bcl-2-overexpressing mice do
not. This suggests that bcl-2 can influence cell
survival after removal of afferent input during the critical period and is consistent with the hypothesis that caspase-3 is one effector of
cell death under these circumstances. These data are the first to
indicate that known apoptotic mediators can play a role in central
neuronal plasticity in models of afferent deprivation.
Key words:
deafferentation; bcl-2; caspase-3; apoptosis; cochlear nucleus; critical period
Copyright © 2002 Society for Neuroscience 0270-6474/02/22114670-05$05.00/0
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