Abstract:
:Although psychotropic drugs act on neurons and glial cells, how glia respond, and whether glial responses are involved in therapeutic effects are poorly understood. Here, we show that fluoxetine (FLX), an anti-depressant, mediates its anti-depressive effect by increasing the gliotransmission of ATP. FLX increased ATP exocytosis via vesicular nucleotide transporter (VNUT). FLX-induced anti-depressive behavior was decreased in astrocyte-selective VNUT-knockout mice or when VNUT was deleted in mice, but it was increased when astrocyte-selective VNUT was overexpressed in mice. This suggests that VNUT-dependent astrocytic ATP exocytosis has a critical role in the therapeutic effect of FLX. Released ATP and its metabolite adenosine act on P2Y11 and adenosine A2b receptors expressed by astrocytes, causing an increase in brain-derived neurotrophic factor in astrocytes. These findings suggest that in addition to neurons, FLX acts on astrocytes and mediates its therapeutic effects by increasing ATP gliotransmission.
journal_name
EBioMedicinejournal_title
EBioMedicineauthors
Kinoshita M,Hirayama Y,Fujishita K,Shibata K,Shinozaki Y,Shigetomi E,Takeda A,Le HPN,Hayashi H,Hiasa M,Moriyama Y,Ikenaka K,Tanaka KF,Koizumi Sdoi
10.1016/j.ebiom.2018.05.036subject
Has Abstractpub_date
2018-06-01 00:00:00pages
72-83issn
2352-3964pii
S2352-3964(18)30201-9journal_volume
32pub_type
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