Region-Specific Reductions in Morphometric Properties and Synaptic Colocalization of Astrocytes Following Cocaine Self-Administration and Extinction.

Region-Specific Reductions in Morphometric Properties and Synaptic Colocalization of Astrocytes Following Cocaine Self-Administration and Extinction.
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DOI:
10.3389/fncel.2018.00246
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发表时间:
2018
影响因子:
5.3
通讯作者:
Reissner KJ
Reissner KJ
中科院分区:
医学2区
文献类型:
--
作者:
Testen A;Sepulveda-Orengo MT;Gaines CH;Reissner KJ

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虽然人们对可卡因使用对大脑奖赏回路中神经元和突触的细胞结构和功能的影响了解很多,但对可卡因对星形胶质细胞的影响知之甚少。鉴于星形胶质细胞在调节神经元和突触功能中发挥的重要作用,缺乏有关星形胶质细胞适应在药物滥用神经病理学中作用的知识是一个重要的研究需求。我们最近发现,星形胶质细胞内的核内的神经胶质细胞(NAc)核心表现出减少的体积,表面积,和突触共定位可卡因自我管理和灭绝后,相比,NAc星形胶质细胞从盐水管理动物。然而,尚不清楚这些可卡因依赖性的星形胶质细胞变化是否普遍存在于整个大脑的奖励回路中,或者代表NAc内的特定适应。也不知道消退期是否是缩回表型所必需的,或者单独的自我给药是否足以驱动这些变化。在目前的研究中,我们已经扩展了我们的评估可卡因自我管理的影响,形态计量学特性和突触共定位的星形胶质细胞周边过程中的前边缘区域的内侧前额叶皮层(PL)和基底外侧核的杏仁核(BLA),这两个已知的也有助于显着的动机行为。此外,为了确定先前观察到的效应的时间维度,我们还检查了最后一次自我给药后NAc内的星形胶质细胞。如前所述,可卡因熄灭大鼠的NAc核心中观察到星形胶质细胞大小和突触共定位减少,但在盐水和可卡因熄灭大鼠之间观察到PL或BLA星形胶质细胞无差异。此外,减少突触共定位的外周过程中的NAc观察到的突触后标记,而不是突触前标记,如前所述。相比之下,没有显着的变化,发现在NAc星形胶质细胞后,单独自我管理。这些结果提供了深入了解可卡因的使用对星形胶质细胞在大脑奖励电路的影响,并告知区域异质性以及星形胶质细胞对可卡因自我管理的响应的时间动态。
While much is known about the effects of cocaine use on the cellular structure and function of neurons and synapses within the brain’s reward circuitry, relatively little is known about the effects of cocaine on astrocytes. Given the significant role that astrocytes play in modulating neuronal and synaptic function, this lack of knowledge regarding the role of astroglial adaptations in the neuropathology of drug abuse represents an important investigative need. We recently showed that astrocytes within the nucleus accumbens (NAc) core exhibit decreased volume, surface area, and synaptic colocalization following cocaine self-administration and extinction, compared to NAc astrocytes from saline-administering animals. However, it is unknown whether these cocaine-dependent changes in astrocytes are ubiquitous throughout the brain’s reward circuitry, or represent specific adaptations within the NAc. It is also not known whether the extinction period is necessary for the retracted phenotype, or whether self-administration alone is sufficient to drive these changes. In the current study, we have extended our assessment of the effects of cocaine self-administration on morphometric properties and synaptic colocalization of astrocyte peripheral processes in the prelimbic region of the medial prefrontal cortex (PL) and basolateral nucleus of the amygdala (BLA), both known to also contribute significantly to motivated behaviors. In addition, in order to pinpoint the temporal dimension of previously observed effects, we also examined astrocytes within the NAc following the last self-administration session. While a reduction of astrocyte size and synaptic colocalization was observed in the NAc core of cocaine-extinguished rats as previously shown, no differences in PL or BLA astrocytes were observed between saline- and cocaine-extinguished rats. Moreover, decreased synaptic colocalization of peripheral processes in the NAc was observed with a post-synaptic marker, instead of a presynaptic marker as used previously. In contrast, no significant changes were found in NAc astrocytes after self-administration alone. These results provide insights into the influence of cocaine use on astrocytes within the brain reward circuitry, and inform both regional heterogeneity as well as temporal dynamics of astrocyte responsiveness to cocaine self-administration.
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