TY - JOUR
T1 - A novel mechanism of depression
T2 - role for connexins
AU - Xia, Cong Yuan
AU - Wang, Zhen Zhen
AU - Yamakuni, Tohru
AU - Chen, Nai Hong
N1 - Funding Information:
This work was supported by the National Natural Science Foundation of China (81573636, 81773924, U1402221, 81560663), Beijing Natural Science Foundation (7182114), PUMC Youth Fund (3332016058), CAMS Innovation Fund for Medical Sciences (CIFMS) (2016-I2M-1–004), the Scientific Research Foundation of the Higher Education Institutions of Hunan Province (15K091), Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study (BZ0150), the State Key Laboratory Fund Open Project (GTZK201610), China Postdoctoral Science Foundation (2013M540066).
PY - 2018/4
Y1 - 2018/4
N2 - Major depressive disorder (MDD) is a chronic and debilitating illness that affects over 350 million people worldwide; however, current treatments have failed to cure or prevent the progress of depression. Increasing evidence suggests a crucial role for connexins in MDD. In this review, we have summarised recent accomplishments regarding the role of connexins, gap junctions, and hemichannels in the aetiology of MDD, and discussed the limitations of current research. A blockage of gap junctions or hemichannels induces depressive behaviour. Possible underlying mechanisms include the regulation of neurosecretory functions and synaptic activity by gap junctions and hemichannels. Gap junctions are functionally inhibited under stress conditions. Conversely, hemichannel permeability is increased. Antidepressants inhibit hemichannel permeability; however, they have contrasting effects on the function of gap junctions under normal conditions and can protect them against stress. In conclusion, the blockage of hemichannels concurrent with improvements in gap junction functionality might be potential targets for depression treatment.
AB - Major depressive disorder (MDD) is a chronic and debilitating illness that affects over 350 million people worldwide; however, current treatments have failed to cure or prevent the progress of depression. Increasing evidence suggests a crucial role for connexins in MDD. In this review, we have summarised recent accomplishments regarding the role of connexins, gap junctions, and hemichannels in the aetiology of MDD, and discussed the limitations of current research. A blockage of gap junctions or hemichannels induces depressive behaviour. Possible underlying mechanisms include the regulation of neurosecretory functions and synaptic activity by gap junctions and hemichannels. Gap junctions are functionally inhibited under stress conditions. Conversely, hemichannel permeability is increased. Antidepressants inhibit hemichannel permeability; however, they have contrasting effects on the function of gap junctions under normal conditions and can protect them against stress. In conclusion, the blockage of hemichannels concurrent with improvements in gap junction functionality might be potential targets for depression treatment.
KW - Connexins
KW - Depression
KW - Gap junction
KW - Hemichannels
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U2 - 10.1016/j.euroneuro.2018.01.009
DO - 10.1016/j.euroneuro.2018.01.009
M3 - Review article
C2 - 29519610
AN - SCOPUS:85042872901
VL - 28
SP - 483
EP - 498
JO - European Neuropsychopharmacology
JF - European Neuropsychopharmacology
SN - 0924-977X
IS - 4
ER -