Stress and glucocorticoids affect the expression of brain-derived neurotrophic factor and neurotrophin-3 mRNAs in the hippocampus

TLDR

Chronic stress causes structural changes and neuronal damage in the hippocampus. The study investigates whether neurotrophic factors contribute to hippocampal neuron vulnerability after stress. The authors used in situ hybridization to assess neurotrophic factor expression following 2‑hour daily immobilization stress in rats. Immobilization stress decreases BDNF mRNA and increases NT‑3 mRNA in the hippocampus, with corticosterone partly mediating these changes, indicating that BDNF and NT‑3 are stress‑responsive genes that may contribute to hippocampal dysfunction.

Abstract

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.