Polysialic acid is required for dopamine D2 receptor-mediated plasticity involving inhibitory circuits of the rat medial prefrontal cortex.
Polysialic acid is required for dopamine D2 receptor-mediated plasticity involving inhibitory circuits of the rat medial prefrontal cortex.
复制标题
DOI：
10.1371/journal.pone.0029516
复制
发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Nacher J
中科院分区：
文献类型：
--
作者：
Castillo-Gómez E;Varea E;Blasco-Ibáñez JM;Crespo C;Nacher J
多巴胺D2受体（D2 R）表达减少、抑制性神经传递功能障碍以及内侧前额叶皮层（mPFC）神经元结构和连接的损伤参与了精神分裂症和抑郁症的发病机制，但这些变化之间的关系尚不清楚。神经细胞粘附分子（PSA-NCAM）的聚唾液酸化形式（一种可塑性相关分子）可能起着联系作用。该分子在皮质中间神经元中表达，多巴胺通过D2 R调节其表达，与突触和抑制性神经传递相关的蛋白质的表达平行，这表明D2 R靶向抗精神病药物/抗抑郁药可能通过影响mPFC抑制回路的可塑性起作用。为了理解PSA-NCAM在这种可塑性中的作用，在皮质PSA耗尽后用D2 R激动剂（PPHT）长期治疗大鼠。PPHT诱导的GAD 67和突触素（SYN）神经元蛋白表达的增加被阻断时，PSA先前被删除，表明PSA-NCAM在这种可塑性的作用。PPHT处理后，表达PSA-NCAM的中间神经元胞体的数量也增加，但属于不同中间神经元亚群的这些细胞的百分比没有变化。皮质锥体神经元不表达PSA-NCAM，但在其胞体周围可发现共表达PSA-NCAM和小白蛋白的斑点。PPHT处理增加了表达PSA-NCAM和小清蛋白的体周点的数量，但降低了共表达SYN的小清蛋白点的百分比。PSA耗竭没有阻断这些对体周区域的影响，但进一步增加了小清蛋白表达点的数量，并增加了共表达SYN和小清蛋白的点的百分比，这表明NCAM的聚唾液酸化可能调节mPFC主神经元的体周抑制。总之，本研究结果表明，多巴胺作用于D2 R影响mPFC中间神经元的结构可塑性，并指出PSA-NCAM在这种重塑中起关键作用。
Decreased expression of dopamine D2 receptors (D2R), dysfunction of inhibitory neurotransmission and impairments in the structure and connectivity of neurons in the medial prefrontal cortex (mPFC) are involved in the pathogenesis of schizophrenia and major depression, but the relationship between these changes remains unclear. The polysialylated form of the neural cell adhesion molecule (PSA-NCAM), a plasticity-related molecule, may serve as a link. This molecule is expressed in cortical interneurons and dopamine, via D2R, modulates its expression in parallel to that of proteins related to synapses and inhibitory neurotransmission, suggesting that D2R-targeted antipsychotics/antidepressants may act by affecting the plasticity of mPFC inhibitory circuits. To understand the role of PSA-NCAM in this plasticity, rats were chronically treated with a D2R agonist (PPHT) after cortical PSA depletion. PPHT-induced increases in GAD67 and synaptophysin (SYN) neuropil expression were blocked when PSA was previously removed, indicating a role for PSA-NCAM in this plasticity. The number of PSA-NCAM expressing interneuron somata also increased after PPHT treatment, but the percentages of these cells belonging to different interneuronal subpopulations did not change. Cortical pyramidal neurons did not express PSA-NCAM, but puncta co-expressing this molecule and parvalbumin could be found surrounding their somata. PPHT treatment increased the number of PSA-NCAM and parvalbumin expressing perisomatic puncta, but decreased the percentage of parvalbumin puncta that co-expressed SYN. PSA depletion did not block these effects on the perisomatic region, but increased further the number of parvalbumin expressing puncta and increased the percentage of puncta co-expressing SYN and parvalbumin, suggesting that the polysialylation of NCAM may regulate perisomatic inhibition of mPFC principal neurons. Summarizing, the present results indicate that dopamine acting on D2R influences structural plasticity of mPFC interneurons and point to PSA-NCAM as a key player in this remodeling.
登录
查看更多内容
影响因子：
34.7
作者：
Arnsten, Amy F. T.
通讯作者：
Arnsten, Amy F. T.
影响因子：
5.3
作者：
Castillo-Gomez, Esther;Gomez-Climent, Maria Angeles;Nacher, Juan
通讯作者：
Nacher, Juan
影响因子：
3.3
作者：
Nacher, J.;Guirado, R.;Hildebrandt, H.
通讯作者：
Hildebrandt, H.
影响因子：
2.5
作者：
Seki, T;Arai, Y
通讯作者：
Arai, Y
影响因子：
2.9
作者：
Nacher, J;Alonso-Llosa, G;McEwen, B
通讯作者：
McEwen, B