Anti-Depressant Fluoxetine Reveals its Therapeutic Effect Via Astrocytes.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 29887330.
- Also identified by DOI 10.1016/j.ebiom.2018.05.036 and PMC identifier 6020856.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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<sub>11</sub> 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.
Medical subject headings
- Depression
- Fluoxetine
- Nucleotide Transport Proteins
- Receptor, Adenosine A2B
- Receptors, Purinergic P2