AI Article Synopsis
- Researchers investigated how an anti-depressant called fluoxetine (FLX) impacts glial cells, particularly their release of ATP, which is important for brain communication.
- The study found that FLX enhances ATP release through a specific transporter (VNUT) in astrocytes, and this action is crucial for its anti-depressant effects.
- Furthermore, manipulating the levels of VNUT in astrocytes affected FLX's ability to alleviate depression, suggesting that targeting glial responses could be key in developing more effective treatments.
Article 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 P2Y 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6020856 | PMC |
| http://dx.doi.org/10.1016/j.ebiom.2018.05.036 | DOI Listing |
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