STRESS AND GLUCOCORTICOIDS AFFECT THE EXPRESSION OF BRAIN-DERIVED NEUROTROPHIC FACTOR AND NEUROTROPHIN-3 MESSENGER-RNAS IN THE HIPPOCAMPUS
STRESS AND GLUCOCORTICOIDS AFFECT THE EXPRESSION OF BRAIN-DERIVED NEUROTROPHIC FACTOR AND NEUROTROPHIN-3 MESSENGER-RNAS IN THE HIPPOCAMPUS
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DOI：
10.1523/jneurosci.15-03-01768.1995
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发表时间：
1995-03-01
影响因子：
5.3
通讯作者：
POST, RM
中科院分区：
文献类型：
--
作者：
SMITH, MA;MAKINO, S;POST, RM
慢性应激会引起结构变化和神经元损伤，尤其是在海马体。由于神经营养因子影响神经元的存活，我们怀疑它们是否与应激后海马神经元的脆弱性增加有关。为了开始研究这种可能性，我们研究了固定应激（2小时/天）的影响，在大鼠脑神经营养因子的表达，使用原位杂交。我们发现，单次或重复制动显着降低脑源性神经营养因子（BDNF）在齿状回和海马的mRNA水平。与此相反，NT-3 mRNA水平的增加，在齿状回和海马在响应重复，但不是急性应激。应激不影响神经营养因子-4或酪氨酸受体激酶（trkB或C）的表达。皮质酮负反馈可能部分导致了应激诱导的BDNF mRNA水平的降低，但应激仍然降低了肾上腺切除大鼠齿状回中的BDNF，这表明应激反应的其他成分也必须有助于观察到的BDNF变化。然而，皮质酮介导的NT-3 mRNA表达的增加似乎是主要负责应激对NT-3的影响。这些研究结果表明，BDNF和NT-3是应激反应基因，并提高了这些或其他生长因子表达的改变可能在海马中产生应激的一些生理和病理生理效应方面很重要的可能性。
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.