Dopamine acting through D2 receptors modulates the expression of PSA-NCAM, a molecule related to neuronal structural plasticity, in the medial prefrontal cortex of adult rats
Dopamine acting through D2 receptors modulates the expression of PSA-NCAM, a molecule related to neuronal structural plasticity, in the medial prefrontal cortex of adult rats
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DOI：
10.1016/j.expneurol.2008.07.018
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发表时间：
2008-11-01
影响因子：
5.3
通讯作者：
Nacher, Juan
中科院分区：
文献类型：
--
作者：
Castillo-Gomez, Esther;Gomez-Climent, Maria Angeles;Nacher, Juan
一种“神经可塑性”假说提出，神经元结构可塑性的变化可能是抑郁症的病因和抗抑郁药作用的基础。内侧前额叶皮层（mPFC）受到这种疾病的影响，并表现出神经细胞粘附分子（PSA-NCAM）的多涎化形式的强烈表达，这是一种主要在中间神经元中表达的可塑性相关分子。单胺类血清素、多巴胺和去甲肾上腺素是抗抑郁作用的主要目标。5 -羟色胺水平的药理学调控突触素和PSA-NCAM在成人mPFC中的表达。然而。多巴胺的抗抑郁作用是否与结构可塑性有关尚未得到很好的探讨。利用免疫组织化学方法，我们研究了多巴胺能纤维和mPFC中表达PSA-NCAM的神经元与D2受体表达的关系。为了评估多巴胺在神经元结构可塑性和油抑制神经传递中的作用，我们分析了6-OHDA消耗皮质多巴胺和D2受体拮抗剂氟哌啶醇或D2受体激动剂PPHT慢性治疗后mPFC中突触素、PSA-NCAM和GAD67的表达。许多多巴胺能纤维与表达PSA-NCAM的神经元密切相关，76%的这些细胞共表达D2受体。氟哌啶醇治疗和6-OHDA注射均可显著降低mPFC中PSA-NCAM、synaptophysin和GAD67的表达。相反，PPHT处理增加了这些分子的表达。我们的研究结果支持抑郁症的“神经可塑性”假说，提示多巴胺作用的油D2受体可能通过改变PSA-NCAM的表达来调节神经元的结构可塑性和抑制神经传递。(C) 2008爱思唯尔公司版权所有。
A "neuroplastic" hypothesis proposes that changes in neuronal structural plasticity may underlie the aetiology of depression and the action of antidepressants. The medial prefrontal cortex (mPFC) is affected by this disorder and shows all intense expression of the polysialylated form of the neural cell adhesion molecule (PSA-NCAM), a plasticity-associated molecule, which is expressed mainly in interneurons. The monoamines serotonin, dopamine and noradrenaline are the principal targets of antidepressant action. Pharmacological manipulation of serotonin levels regulates synaptophysin and PSA-NCAM expression in the adult mPFC. However. the involvement of structural plasticity oil the antidepressant effects of dopamine has not been well explored yet. Using immunohistochemistry, we have studied the relationship between dopaminergic fibers and PSA-NCAM expressing neurons in the mPFC and the expression of D2 receptors. In order to evaluate the effects of dopamine in neuronal structural plasticity and oil inhibitory neurotransmission, we have analyzed the expression of synaptophysin, PSA-NCAM and GAD67 in the mPFC after cortical dopamine depletion with 6-OHDA and after chronic treatments with the D2 receptor antagonist haloperidol or the D2 receptor agonist PPHT Many dopaminergic fibers were observed in close apposition to PSA-NCAM expressing neurons and 76% of these cells co-expressed D2 receptor. Both haloperiodol treatment and 6-OHDA injection reduced significantly PSA-NCAM, synaptophysin and GAD67 expression in the mPFC. Conversely, PPHT treatment increased the expression of these molecules. Our results give Support to the "neuroplastic" hypothesis of depression, suggesting that dopamine acting oil D2 receptors may modulate neuronal structural plasticity and inhibitory neurotransmission through changes in PSA-NCAM expression. (C) 2008 Elsevier Inc. All rights reserved.