Department of Neuroscience, Medical University of South Carolina, Charleston, SC 29464, USA.
Department of Neuroscience, Medical University of South Carolina, Charleston, SC 29464, USA.
Trends Pharmacol Sci. 2022 Jan;43(1):56-68. doi: 10.1016/j.tips.2021.10.006. Epub 2021 Nov 6.
Treatments for substance use and stress disorders are based on ameliorating behavioral symptoms, not on reversing the synaptic pathology that has the potential to cure disorders. This failing arises in part from a research focus on how pre- and postsynaptic physiology is changed even though key neuropathology exists in the perisynaptic neuropil that homeostatically regulates synaptic transmission. We explore recent findings from the substance use and stress disorder literature pointing to a key role for perisynaptic astroglia and signaling in the extracellular matrix (ECM) in regulating synaptic pathology. We conclude that drugs and stress initiate long-lasting changes in brain synapses via enduring neuroadaptations in astroglia and the ECM, and that modulating extrasynaptic regulators may be therapeutically useful.
物质使用和压力障碍的治疗方法基于改善行为症状，而不是逆转有可能治愈障碍的突触病理学。这种失败部分源于研究重点关注的是如何改变突触前和突触后生理学，尽管突触周神经胶质细胞中存在关键神经病理学，它可以对突触传递进行稳态调节。我们探讨了物质使用和压力障碍文献中的最新发现，这些发现指出了突触周星形胶质细胞和细胞外基质 (ECM) 中的信号在调节突触病理学方面的关键作用。我们的结论是，药物和压力通过星形胶质细胞和 ECM 中的持久神经适应性，在大脑突触中引发持久的变化，而调节细胞外调节剂可能具有治疗意义。
