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Journal of Neuroscience, Vol 15, 1768-1777, Copyright © 1995 by Society for Neuroscience
Stress and glucocorticoids affect the expression of brain-derived neurotrophic factor and neurotrophin-3 mRNAs in the hippocampus
MA Smith, S Makino, R Kvetnansky and RM Post
Biological Psychiatry Branch, National Institute of Mental Health, Bethesda, Maryland 20892.
Chronic stress produces structural changes and neuronal damage especially
in the hippocampus. Because neurotrophic factors affect neuron survival, we
questioned whether they might be relevant to the heightened vulnerability
of hippocampal neurons following stress. To begin investigating this
possibility, we examined the effects of immobilization stress (2 hr/d) on
the expression of neurotrophic factors in rat brains using in situ
hybridization. We found that single or repeated immobilization markedly
reduced brain-derived neurotrophic factor (BDNF) mRNA levels in the dentate
gyrus and hippocampus. In contrast, NT-3 mRNA levels were increased in the
dentate gyrus and hippocampus in response to repeated but not acute stress.
Stress did not affect the expression of neurotrophin-4, or tyrosine
receptor kinases (trkB or C). Corticosterone negative feedback may have
contributed in part to the stress-induced decreases in BDNF mRNA levels,
but stress still decreased BDNF in the dentate gyrus in adrenalectomized
rats suggesting that additional components of the stress response must also
contribute to the observed changes in BDNF. However,
corticosterone-mediated increases in NT-3 mRNA expression appeared to be
primarily responsible for the effects of stress on NT-3. These findings
demonstrate that BDNF and NT-3 are stress-responsive genes and raise the
possibility that alterations in the expression of these or other growth
factors might be important in producing some of the physiological and
pathophysiological effects of stress in the hippocampus.
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