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Role of Dopamine D2 Receptor in Stress-Induced Myelin Loss.

ABSTRACT: 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 ?-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/?-catenin signaling pathway in association with DA signaling through D2R.

SUBMITTER: Choi MH

PROVIDER: S-EPMC5599541 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Role of Dopamine D2 Receptor in Stress-Induced Myelin Loss.

Choi Mi-Hyun MH Na Ji Eun JE Yoon Ye Ran YR Lee Hyo Jin HJ Yoon Sehyoun S Rhyu Im Joo IJ Baik Ja-Hyun JH

Scientific reports 20170914 1

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<sup>-/-</sup>) 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<sup>-/-</sup> mice, which was already lower than that in WT mi ...[more]

PMID: 28912499

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Project description:Methamphetamine (METH) abuse is a serious public health issue. Of particular concern are findings that repeated high-dose administrations of METH cause persistent dopaminergic deficits in rodents, nonhuman primates, and humans. Previous studies have also revealed that METH treatment causes alterations in the dopamine transporter (DAT), including the formation of higher molecular mass DAT-associated complexes. The current study extends these findings by examining mechanisms underlying DAT complex formation. The association among DAT complex formation and other METH-induced phenomena, including alterations in vesicular monoamine transporter 2 (VMAT2) immunoreactivity, astrocytic activation [as assessed by increased glial fibrillary acidic protein (GFAP) immunoreactivity], and persistent dopaminergic deficits was also explored. Results revealed that METH-induced DAT complex formation and reductions in VMAT2 immunoreactivity precede increases in GFAP immunoreactivity. Furthermore, and as reported previously for DAT complexes, pretreatment with the D2 receptor antagonist eticlopride [S-(-)-3-chloro-5-ethyl-N-[(1-ethyl-2-pyrrolidinyl)methyl]-6-hydroxy-2-methoxybenzamide hydrochloride] attenuated the decrease in VMAT2 immunoreactivity as assessed 24 h after METH treatment. DAT complexes distinct from those present 24 h after METH treatment, decreases in VMAT2 immunoreactivity, and increased GFAP immunoreactivity were present 48 to 72 h after METH treatment. Pretreatment with eticlopride attenuated each of these phenomena. Finally, DAT complexes were present 7 days after METH treatment, a time point at which VMAT2 and DAT monomer immunoreactivity were also reduced. Eticlopride pretreatment attenuated each of these phenomena. These findings provide novel insight into not only receptor-mediated mechanisms underlying the effects of METH but also the interaction among factors that probably are associated with the persistent dopaminergic deficits caused by the stimulant.

Dataset Information

Role of Dopamine D2 Receptor in Stress-Induced Myelin Loss.

Publications

Role of Dopamine D2 Receptor in Stress-Induced Myelin Loss.

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