O'Reilly, Kally C., Trent, Simon ![]() |
Abstract
In addition to their established role in nervous system development, vitamin A and related retinoids are emerging as regulators of adult brain function. Accutane (13-cis-retinoic acid, isotretinoin) treatment has been reported to increase depression in humans. Recently, we showed that chronic administration of 13-cis-retinoic acid (13-cis-RA) to adolescent male mice increased depression-related behaviors. Here, we have examined whether 13-cis-RA regulates components involved in serotonergic neurotransmission in vitro. We used the RN46A-B14 cell line, derived from rat embryonic raphe nuclei. This cell line synthesizes serotonin (5-hydroxytryptamine, 5-HT) and expresses the 5-HT1A receptor and the serotonin reuptake transporter (SERT). Cells were treated with 0, 2.5, or 10 μM 13-cis-RA for 48 or 96 hrs, and the levels of 5-HT; its metabolite, 5-hydroxyindoleacetic acid (5HIAA); 5-HT1A receptor; and SERT were determined. Treatment with 13-cis-RA for 96 hrs increased the intracellular levels of 5-HT and tended to increase intra-cellular 5HIAA levels. Furthermore, 48 hrs of treatment with 2.5 and 10 μM 13-cis-RA significantly increased 5-HT1A protein to 168.5 ± 20.0% and 148.7 ± 2.2% of control respectively. SERT protein levels were significantly increased to 142.5 ± 11.1% and 119.2 ± 3.6% of control by 48 hrs of treatment with 2.5 and 10 μM of 13-cis-RA respectively. Increases in both 5-HT1A receptor and SERT proteins may lead to decreased serotonin availability at synapses. Such an effect of 13-cis-RA could contribute to the increased depression-related behaviors we have shown in mice.
Item Type: | Article |
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Status: | Published |
Schools: | Psychology Neuroscience and Mental Health Research Institute (NMHRI) |
Uncontrolled Keywords: | 13-cis-retinoic acid; depression; serotonin; 5-HT1A receptor; SERT |
ISSN: | 1535-3702 |
Last Modified: | 20 Oct 2022 09:50 |
URI: | https://orca.cardiff.ac.uk/id/eprint/33276 |
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