Dopaminergic systems play a major role in reward-related behavior and dysregulation of dopamine (DA) systems can cause several mental disorders, including depression. We previously reported that dopamine D2 receptor knockout (D2R-/-) mice display increased anxiety and depression-like behaviors upon chronic stress. Here, we observed that chronic stress caused myelin loss in wild-type (WT) mice, while the myelin level in D2R-/- mice, which was already lower than that in WT mice, was not affected upon stress. Fewer mature oligodendrocytes (OLs) were observed in the corpus callosum of stressed WT mice, while in D2R-/- mice, both the control and stressed group displayed a decrease in the number of mature OLs. We observed a decrease in the number of active β-catenin (ABC)-expressing and TCF4-expressing cells among OL lineage cells in the corpus callosum of stressed WT mice, while such regulation was not found in D2R-/- mice. Administration of lithium normalized the behavioral impairments and myelin damage induced by chronic stress in WT mice, and restored the number of ABC-positive and TCF4-positive OLs, while such effect was not found in D2R-/- mice. Together, our findings indicate that chronic stress induces myelin loss through the Wnt/β-catenin signaling pathway in association with DA signaling through D2R.
Bibliographical noteFunding Information:
We thank staff of Gyerim Experimental Animal Resource Center for animal care and technical assistance. This study was supported by the Brain Research Program (2013M3C7A1056101), Bio & Medical Technology Development Program (2013M3A9D5072550 and 2016M3A9D5A01952412), Mid-Career Researcher Program (2017R1A2B4008875), Science Research Center (2015R1A5A1009024) of National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT, Future Planning of the Republic of Korea and by a Korea University grant.
© 2017 The Author(s).
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