Induction of brain‐derived neurotrophic factor by convulsant drugs in the rat brain: involvement of region‐specific voltage‐dependent calcium channels
Induction of brain‐derived neurotrophic factor by convulsant drugs in the rat brain: involvement of region‐specific voltage‐dependent calcium channels
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大鼠脑中惊厥药物诱导脑源性神经营养因子：区域特异性电压依赖性钙通道的参与
DOI：
10.1046/j.1471-4159.2001.00138.x
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发表时间：
2001
影响因子：
4.7
通讯作者：
Kanefusa Kato
中科院分区：
文献类型：
--
作者：
R. Katoh‐Semba;I. Takeuchi;Y. Inaguma;S. Ichisaka;Y. Hata;T. Tsumoto;M. Iwai;K. Mikoshiba;Kanefusa Kato
正常老年大鼠海马脑源性神经营养因子（BDNF）水平高于年轻大鼠，这表明在衰老过程中维持相当水平的海马BDNF对维持正常海马功能至关重要。为了阐明内源性BDNF增加的可能机制，研究了在全身施用各种惊厥剂后大鼠脑中BDNF水平的变化;兴奋毒性谷氨酸激动剂、NMDA、红藻氨酸和（+/-）-α-氨基-3-羟基-5-甲基异恶唑-4-丙酸（AMPA）; GABA受体拮抗剂、印防己毒素、戊四唑（PTZ）和林替卡松（linoclavin）。（γ-六氯环己烷）和l型电压依赖性钙通道激动剂BAY-K 8644。红藻氨酸和AMPA，而不是NMDA，引起大鼠海马和内嗅皮层BDNF蛋白的显着增加。印防己毒素，戊四氮和林替卡松刺激BDNF的生产，内嗅皮层，也在海马的大鼠表现出非常严重的惊厥。另一方面，BAY-K 8644治疗增加了新皮质和内嗅皮质中的BDNF水平。分别在给予红藻氨酸、PTZ和BAY-K 8644后12-24 h、8-16 h和6 h观察到BDNF蛋白的最大水平。 海人酸刺激突触前海马颗粒神经元的BDNF合成，但不刺激具有其受体的突触后神经元的BDNF合成，而PTZ和BAY-K 8644分别在内嗅皮层（海马颗粒神经元）和整个皮层的突触后神经元中产生相同的作用。硝苯地平几乎完全抑制BAY-K 8644的作用，但不抑制PTZ的作用。ω-芋螺毒素GVIA和DCG-IV部分阻断红藻氨酸诱导的BDNF增强，分别表明l-型和N-型电压依赖性钙通道的参与。此外，d-肌-肌醇-1，4，5-三磷酸受体基因缺陷小鼠海马中的BDNF水平与对照组相同区域中的BDNF水平几乎没有差异，这表明通过该受体的细胞内钙增加几乎没有参与。BAY-K 8644，而不是红藻氨酸或PTZ，刺激环AMP反应元件结合蛋白的磷酸化。我们的研究结果表明，惊厥依赖性刺激BDNF的产生和区域特异性电压依赖性钙通道的参与。
A high level of hippocampal brain‐derived neurotrophic factor (BDNF) in normally aged as compared with young rats suggests that it is important to maintain a considerable level of hippocampal BDNF during aging in order to keep normal hippocampal functions. To elucidate possible mechanisms of endogenous BDNF increase, changes in levels of BDNF were studied in the rat brain following systemic administration of various convulsant agents; excitotoxic glutamate agonists, NMDA, kainic acid and (+/–)‐α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid (AMPA); GABA receptor antagonists, picrotoxin, pentylenetetrazole (PTZ) and lindane (γ‐hexachlorocyclohexane); and l‐type voltage‐dependent calcium channel agonist, BAY‐K 8644. Kainic acid and AMPA, but not NMDA, caused remarkable increases in BDNF protein in the rat hippocampus and entorhinal cortex. Picrotoxin, PTZ and lindane stimulated BDNF production in the entorhinal cortex and also in the hippocampus of rats showing very severe convulsions. On the other hand, BAY‐K 8644 treatment increased BDNF levels in the neocortex and entorhinal cortex. Maximal levels of BDNF protein were observed at 12–24 h, 8–16 h and 6 h following administration of kainic acid, PTZ and BAY‐K 8644, respectively. Kainic acid stimulated BDNF synthesis in presynaptic hippocampal granule neurons, but not in postsynaptic neurons with its receptors, while PTZ and BAY‐K 8644 produced the same effects in postsynaptic neurons in the entorhinal cortex (in granule neurons in the hippocampus) and in the whole cortex, respectively. Nifedipine inhibited almost completely BAY‐K 8644, but not PTZ, effects. ω‐Conotoxin GVIA and DCG‐IV partially blocked kainic acid‐induced enhancement of BDNF, indicating involvement of l‐type and N‐type voltage‐dependent calcium channels, respectively. In addition, BDNF levels in the hippocampus of mice deficient in d‐myo‐inositol‐1,4,5‐triphosphate receptor gene were scarcely different from those in the same region of controls, suggesting little involvement of intracellular calcium increase through this receptor. BAY‐K 8644, but not kainic acid or PTZ, stimulated the phosphorylation of cyclic AMP responsive element binding protein. Our results indicate convulsant‐dependent stimulation of BDNF production and involvement of region‐specific voltage‐dependent calcium channels.
DOI：
10.1073/pnas.90.19.8802
发表时间：
1993-10-01
影响因子：
11.1
作者：
METSIS, M;TIMMUSK, T;PERSSON, H
通讯作者：
PERSSON, H
NMDA 受体的激活会增加海马结构中脑源性神经营养因子 (BDNF) mRNA 的表达。
影响因子：
1.7
作者：
Gwag,BJ;Springer,JE
通讯作者：
Springer,JE
影响因子：
56.9
作者：
GHOSH, A;CARNAHAN, J;GREENBERG, ME
通讯作者：
GREENBERG, ME