| First Author | Zhou W | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 8 | Pages | e43262 |
| PubMed ID | 22912839 | Mgi Jnum | J:190060 |
| Mgi Id | MGI:5447896 | Doi | 10.1371/journal.pone.0043262 |
| Citation | Zhou W, et al. (2012) The effects of glycogen synthase kinase-3beta in serotonin neurons. PLoS One 7(8):e43262 |
| abstractText | Glycogen synthase kinase-3 (GSK3) is a constitutively active protein kinase in brain. Increasing evidence has shown that GSK3 acts as a modulator in the serotonin neurotransmission system, including direct interaction with serotonin 1B (5-HT1B) receptors in a highly selective manner and prominent modulating effect on 5-HT1B receptor activity. In this study, we utilized the serotonin neuron-selective GSK3beta knockout (snGSK3beta-KO) mice to test if GSK3beta in serotonin neurons selectively modulates 5-HT1B autoreceptor activity and function. The snGSK3beta-KO mice were generated by crossbreeding GSK3beta-floxed mice and ePet1-Cre mice. These mice had normal growth and physiological characteristics, similar numbers of tryptophan hydroxylase-2 (TpH2)-expressing serotonin neurons, and the same brain serotonin content as in littermate wild type mice. However, the expression of GSK3beta in snGSK3beta-KO mice was diminished in TpH2-expressing serotonin neurons. Compared to littermate wild type mice, snGSK3beta-KO mice had a reduced response to the 5-HT1B receptor agonist anpirtoline in the regulation of serotonergic neuron firing, cAMP production, and serotonin release, whereas these animals displayed a normal response to the 5-HT1A receptor agonist 8-OH-DPAT. The effect of anpirtoline on the horizontal, center, and vertical activities in the open field test was differentially affected by GSK3beta depletion in serotonin neurons, wherein vertical activity, but not horizontal activity, was significantly altered in snGSK3beta-KO mice. In addition, there was an enhanced anti-immobility response to anpirtoline in the tail suspension test in snGSK3beta-KO mice. Therefore, results of this study demonstrated a serotonin neuron-targeting function of GSK3beta by regulating 5-HT1B autoreceptors, which impacts serotonergic neuron firing, serotonin release, and serotonin-regulated behaviors. |
