Poggi Giulia, Albiez Jamie, Pryce Christopher R
Preclinical Laboratory for Translational Research Into Affective Disorders, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Switzerland.
Neuroscience Center Zurich, University of Zurich and ETH Zurich, Switzerland.
Neurobiol Stress. 2022 Apr 20;18:100451. doi: 10.1016/j.ynstr.2022.100451. eCollection 2022 May.
Stress-related neuropsychiatric disorders present with excessive processing of aversive stimuli. Whilst underlying pathophysiology remains poorly understood, within- and between-regional changes in oligodendrocyte (OL)-myelination status in anterior cingulate cortex and amygdala (ACC-AMY network) could be important. In adult mice, a 15-day chronic social stress (CSS) protocol leads to increased aversion responsiveness, accompanied by increased resting-state functional connectivity between, and reduced oligodendrocyte- and myelin-related transcript expression within, medial prefrontal cortex and amygdala (mPFC-AMY network), the analog of the human ACC-AMY network. In the current study, young-adult male C57BL/6 mice underwent CSS or control handling (CON). To assess OL proliferation-maturation, mice received 5-ethynyl-2'-deoxyuridine via drinking water across CSS/CON and brains were collected on day 16 or 31. In mPFC, CSS decreased the density of proliferative OL precursor cells (OPCs) at days 16 and 31. CSS increased mPFC myelin basic protein (MBP) integrated density at day 31, as well as increasing myelin thickness as determined using transmission electron microscopy, at day 16. In AMY, CSS increased the densities of total CC1 OLs (day 31) and CC1/ASPA OLs (days 16 and 31), whilst decreasing the density of proliferative OPCs at days 16 and 31. CSS was without effect on AMY MBP content and myelin thickness, at days 16 and 31. Therefore, CSS impacts on the OL lineage in mPFC and AMY and to an extent that, in mPFC at least, leads to increased myelination. This increased myelination could contribute to the excessive aversion learning and memory that occur in CSS mice and, indeed, human stress-related neuropsychiatric disorders.
与应激相关的神经精神疾病表现为对厌恶刺激的过度处理。虽然其潜在的病理生理学仍知之甚少，但前扣带回皮质和杏仁核（ACC-AMY网络）中少突胶质细胞（OL）髓鞘形成状态的区域内和区域间变化可能很重要。在成年小鼠中，为期15天的慢性社会应激（CSS）方案会导致厌恶反应性增加，同时内侧前额叶皮质和杏仁核（mPFC-AMY网络，即人类ACC-AMY网络的类似物）之间的静息态功能连接增加，而少突胶质细胞和髓鞘相关转录本表达减少。在本研究中，年轻成年雄性C57BL/6小鼠接受了CSS或对照处理（CON）。为了评估OL的增殖-成熟情况，小鼠在整个CSS/CON期间通过饮用水摄入5-乙炔基-2'-脱氧尿苷，并在第16天或第31天收集大脑。在mPFC中，CSS在第16天和第31天降低了增殖性OL前体细胞（OPC）的密度。CSS在第31天增加了mPFC髓鞘碱性蛋白（MBP）的积分密度，并且在第16天通过透射电子显微镜测定增加了髓鞘厚度。在AMY中，CSS在第31天增加了总CC1 OLs的密度以及在第16天和第31天增加了CC1/ASPA OLs的密度，同时在第16天和第31天降低了增殖性OPC的密度。在第16天和第31天，CSS对AMY的MBP含量和髓鞘厚度没有影响。因此，CSS影响mPFC和AMY中的OL谱系，并且至少在mPFC中，这种影响程度导致髓鞘形成增加。这种增加的髓鞘形成可能导致CSS小鼠以及人类应激相关神经精神疾病中出现的过度厌恶学习和记忆。
