Reversal of brain injury-induced prefrontal glutamic acid decarboxylase expression and working memory deficits by D1 receptor antagonism
Reversal of brain injury-induced prefrontal glutamic acid decarboxylase expression and working memory deficits by D1 receptor antagonism
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DOI：
10.1523/jneurosci.4687-05.2006
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发表时间：
2006-04-19
影响因子：
5.3
通讯作者：
Dash, PK
中科院分区：
文献类型：
--
作者：
Kobori, N;Dash, PK
工作记忆(WM)，即在脑海中暂时记住信息的能力，对于脑损伤患者经常受损的高级认知功能是必不可少的。在这些患者中，导致WM缺陷的细胞和分子机制尚不清楚，这种缺陷可以在没有明显损害的情况下表现出来。人和猴子的背外侧前额叶皮质和啮齿动物的内侧前额叶皮质(MPFC)的功能对WM至关重要。我们证明，大鼠大脑皮质撞击伤可导致长期的WM损伤，这与伤后1个月内mPFC中GABA合成酶谷氨酸脱羧酶67(GAD67)水平的升高有关。损伤后14d单次注射多巴胺D-1拮抗剂足以降低GAD67水平，恢复WM至少1周。这些发现表明，前额叶神经元活动的抑制导致WM缺陷，减少GAD67表达的策略可以延长脑损伤患者的WM改善。
Working memory (WM), the ability to transiently hold information in mind, is essential for high- level cognitive functions that are often impaired in brain- injured patients. The cellular and molecular mechanisms contributing to WM deficits, which can manifest in the absence of overt damage, in these patients are unknown. The function of the dorsolateral prefrontal cortex in humans and monkeys, and the medial prefrontal cortex (mPFC), in rodents is critical for WM. We demonstrate that controlled cortical impact injury of rats causes a long- lasting WM impairment that is associated with increased levels of the GABA- synthesizing enzyme glutamic acid decarboxylase 67 (GAD67) in the mPFC for up to 1 month after injury. A single administration of dopamine D-1 antagonists at 14 d after injury is sufficient to decrease GAD67 levels and restore WM for at least 1 week. These findings indicate that inhibition of prefrontal neuronal activity contributes to WM deficits and that strategies to reduce GAD67 expression can offer prolonged WM improvement in brain- injured patients.