Chronic Unpredictable Stress Reduces Immunostaining for Connexins 43 and 30 and Myelin Basic Protein in the Rat Prelimbic and Orbitofrontal Cortices.
Chronic Unpredictable Stress Reduces Immunostaining for Connexins 43 and 30 and Myelin Basic Protein in the Rat Prelimbic and Orbitofrontal Cortices.
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DOI：
10.1177/2470547018814186
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发表时间：
2018-01-01
期刊：
影响因子：
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通讯作者：
Rajkowska, Grazyna
中科院分区：
文献类型：
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作者：
Miguel-Hidalgo, Jose Javier;Moulana, Mohadetheh;Rajkowska, Grazyna
背景：在重度抑郁症中，背外侧前额叶和眶额皮质的星形胶质细胞和少突胶质细胞发生病理改变。在应激（重度抑郁症危险因素）大鼠模型中，前边缘皮质中的星形胶质细胞间隙连接蛋白连接蛋白 43 (Cx43) 减少。星形胶质细胞连接蛋白被认为强烈影响中枢神经系统中髓磷脂的维持。然而，目前尚不清楚 Cx43 和其他主要星形胶质细胞连接蛋白 Cx30 中的应激相关变化是否发生在眶额皮质中，或者连接蛋白变化是否与髓鞘形成紊乱同时发生。 方法：对经受 35 天慢性不可预测应激的大鼠和对照组（n = 6/组）的包含前边缘皮层和眶额皮质的冰冻切片进行 Cx43、Cx30 和 Cx43、Cx30 的免疫标记。髓磷脂碱性蛋白。测量边缘前皮质和眶额皮质中 Cx43 或 Cx30 免疫反应性斑点的密度和髓鞘碱性蛋白免疫反应性面积分数，并用 t 检验或 Pearson 相关性分析结果。 结果：慢性不可预测应激处理组大鼠边缘前皮质和眶额皮质中 Cx43 和 Cx30 阳性斑点的密度低于对照大鼠。在这两个区域中，慢性不可预测应激动物的髓磷脂碱性蛋白免疫反应性面积分数也较低。髓磷脂碱性蛋白面积分数与眶额皮层中的 Cx43 阳性点的密度以及前边缘皮层中的 Cx30 点的密度呈正相关。 结论：大鼠前边缘皮层和眶额皮层在慢性不可预测应激后 Cx43 和 Cx30 较低，表明星形胶质细胞间隙连接密度的降低可能会推广到整个前额皮层。 Cx43、Cx30 和髓磷脂碱性蛋白免疫标记结构的同时减少与星形胶质细胞间隙连接蛋白的变化和抑郁症中髓磷脂形态紊乱有关的机制一致。
BACKGROUND: Astrocytes and oligodendrocytes are pathologically altered in dorsolateral prefrontal and orbitofrontal cortices in major depressive disorder. In rat models of stress (major depressive disorder risk factor) astrocyte gap junction protein connexin 43 (Cx43) is reduced in the prelimbic cortex. Astrocyte connexins are recognized to strongly influence myelin maintenance in the central nervous system. However, it is unknown whether stress-related changes in Cx43 and the other major astrocyte connexin, Cx30, occur in the orbitofrontal cortex, or whether connexin changes are concurrent with disturbances in myelination.METHODS: Frozen sections containing prelimbic cortex and orbitofrontal cortex of rats subjected to 35 days of chronic unpredictable stress and controls (n = 6/group) were immunolabeled for Cx43, Cx30, and myelin basic protein. Density of Cx43 or Cx30 immunoreactive puncta and area fraction of myelin basic protein immunoreactivity were measured in prelimbic cortex and orbitofrontal cortex and results analyzed with t test or Pearson correlations.RESULTS: Density of Cx43- and Cx30-positive puncta in both prelimbic cortex and orbitofrontal cortex was lower in chronic unpredictable stress-treated than in control rats. In both regions, the area fraction of myelin basic protein immunoreactivity was also lower in chronic unpredictable stress animals. Myelin basic protein area fraction was positively correlated with the density of Cx43-positive puncta in orbitofrontal cortex, and with Cx30 puncta in prelimbic cortex.CONCLUSION: Low Cx43 and Cx30 after chronic unpredictable stress in rat prelimbic cortex and orbitofrontal cortex suggests that reduced astrocytic gap junction density may generalize to the entire prefrontal cortex. Concurrent reduction of Cx43-, Cx30-, and myelin basic protein-immunolabeled structures is consistent with a mechanism linking changes in astrocyte gap junction proteins and disturbed myelin morphology in depression.