Endogenous glucocorticoids are essential for maintaining prefrontal cortical cognitive function
Endogenous glucocorticoids are essential for maintaining prefrontal cortical cognitive function
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DOI：
10.1523/jneurosci.0086-04.2004
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发表时间：
2004-06-16
影响因子：
5.3
通讯作者：
Tabira, T
中科院分区：
文献类型：
--
作者：
Mizoguchi, K;Ishige, A;Tabira, T
糖皮质激素在维持许多脑功能方面很重要。虽然他们的受体分布丰富，整个大脑，包括前额叶皮质（PFC），目前还不清楚糖皮质激素的功能，特别是在PFC的认知加工方面。有证据表明PFC认知缺陷，如工作记忆障碍，在一些与压力相关的神经精神疾病，包括抑郁症，精神分裂症和帕金森氏病。还观察到下丘脑-垂体-肾上腺（HPA）系统的破坏，其特征在于减弱的糖皮质激素负反馈。在大鼠中，慢性应激诱导工作记忆障碍作为减少多巴胺能传递的结果在PFC。这些慢性应激大鼠也表现出HPA中断，这是由减少糖皮质激素的反应在PFC。这些研究结果牵连减少糖皮质激素的行动在工作记忆障碍。在本研究中，我们检查了肾上腺切除术（ADX）抑制内源性糖皮质激素对大鼠工作记忆的影响，并探讨了PFC多巴胺能活动在记忆中的参与。ADX损害工作记忆，减少多巴胺的释放，并上调D-1受体的PFC。这些功能障碍被皮质酮替代，再现正常的生理血浆水平，表明抑制糖皮质激素导致这些功能障碍。此外，ADX诱导的工作记忆障碍得到改善，PFC内输注的D-1受体激动剂，SKF 81297。因此，抑制糖皮质激素损害工作记忆通过D-1受体介导的低多巴胺能机制在PFC。这一发现表明，内源性糖皮质激素是必不可少的，维持PFC的认知功能，并表明HPA中断有助于PFC的认知缺陷。
Glucocorticoid hormones are important in the maintenance of many brain functions. Although their receptors are distributed abundantly throughout the brain, including the prefrontal cortex (PFC), it is not clear how glucocorticoid functions, particularly with regard to cognitive processing in the PFC. There is evidence of PFC cognitive deficits such as working memory impairment in several stress-related neuropsychiatric disorders, including depression, schizophrenia, and Parkinson's disease. Disruption of the hypothalamo-pituitary-adrenal ( HPA) system, which is characterized by attenuated glucocorticoid negative feedback, is also observed. In rats, chronic stress induces working memory impairment as a result of decreased dopaminergic transmission in the PFC. These chronically stressed rats also show HPA disruption; this is caused in part by a reduced glucocorticoid response in the PFC. These findings implicate reduced glucocorticoid actions in working memory impairment. In the present study, we examined the effects of the suppression of endogenous glucocorticoids by adrenalectomy (ADX) on working memory in rats and explored the involvement of PFC dopaminergic activities in memory. The ADX impaired working memory, decreased dopamine release, and upregulated D-1 receptors in the PFC. These dysfunctions were prevented by corticosterone replacement that reproduced normal physiological plasma levels, indicating that suppression of glucocorticoids causes these dysfunctions. Moreover, the ADX-induced working memory impairment was ameliorated by intra-PFC infusions of a D-1 receptor agonist, SKF 81297. Thus, suppression of glucocorticoids impaired working memory through a D-1 receptor-mediated hypodopaminergic mechanism in the PFC. This finding indicates that endogenous glucocorticoids are essential for maintaining PFC cognitive function and suggests that HPA disruption contributes to PFC cognitive deficits.