Serotonin receptor activation leads to neurite outgrowth and neuronal survival - PubMed (original) (raw)
Serotonin receptor activation leads to neurite outgrowth and neuronal survival
Ashwana D Fricker et al. Brain Res Mol Brain Res. 2005.
Abstract
Serotonin 5-HT1 receptors are implicated in anxiety and depression. These receptors belong to the family A of G-protein-coupled receptors and couple to inhibitory G-proteins. Recent studies show that chronic activation of 5-HT1A receptors leads to proliferation of hippocampal neurons suggesting that neurogenesis contributes to the effects of antidepressants. However, the molecular mechanisms and pathways involved are not understood. We used Neuro 2A cells transfected with 5-HT1A receptors and SK-N-SH cells endogenously expressing the receptor to examine the effect of receptor activation on neuronal survival and neurite outgrowth. We find that receptor activation leads to increased neurite outgrowth that can be blocked by the receptor selective antagonist and by treatment with pertussis toxin or lactacystin implicating inhibitory G-proteins and proteasomal degradation in this process. Interestingly, the small G-protein Rap and the transcription factor STAT-3 are also involved since reducing the levels of Rap1 (using small interfering RNA) or STAT-3 (using dominant negative STAT3) significantly blocks 5-HT1A-receptor-mediated neurite outgrowth. The observed increase in the phosphorylation of Src and STAT-3, at sites leading to their activation, further supports a crucial role for these proteins in neurite outgrowth. We also find that prolonged activation of endogenous 5-HT1A receptors leads to increased cell survival even under starving conditions; this is completely blocked by co-treatment with the antagonist. Taken together, these findings indicate that activation of the 5-HT1A receptor leads to a number of neurotropic events by activating a series of signal transduction molecules leading to long-term changes required for neurogenesis.
Similar articles
- δ-opioid receptor activation leads to neurite outgrowth and neuronal differentiation via a STAT5B-Gαi/o pathway.
Georganta EM, Tsoutsi L, Gaitanou M, Georgoussi Z. Georganta EM, et al. J Neurochem. 2013 Nov;127(3):329-41. doi: 10.1111/jnc.12386. Epub 2013 Sep 18. J Neurochem. 2013. PMID: 23906478 - Mevastatin-induced neurite outgrowth of neuroblastoma cells via activation of EGFR.
Evangelopoulos ME, Weis J, Krüttgen A. Evangelopoulos ME, et al. J Neurosci Res. 2009 Jul;87(9):2138-44. doi: 10.1002/jnr.22025. J Neurosci Res. 2009. PMID: 19224573 - Role of the Go/i signaling network in the regulation of neurite outgrowth.
He JC, Neves SR, Jordan JD, Iyengar R. He JC, et al. Can J Physiol Pharmacol. 2006 Jul;84(7):687-94. doi: 10.1139/y06-025. Can J Physiol Pharmacol. 2006. PMID: 16998532 Review. - Roles of extracellular signal-regulated kinase and Akt signaling in coordinating nuclear transcription factor-kappaB-dependent cell survival after serotonin 1A receptor activation.
Hsiung SC, Tamir H, Franke TF, Liu KP. Hsiung SC, et al. J Neurochem. 2005 Dec;95(6):1653-66. doi: 10.1111/j.1471-4159.2005.03496.x. Epub 2005 Oct 20. J Neurochem. 2005. PMID: 16238696 - Control of myeloid differentiation and survival by Stats.
Smithgall TE, Briggs SD, Schreiner S, Lerner EC, Cheng H, Wilson MB. Smithgall TE, et al. Oncogene. 2000 May 15;19(21):2612-8. doi: 10.1038/sj.onc.1203477. Oncogene. 2000. PMID: 10851060 Review.
Cited by
- Chronic Treatment with Serotonin Selective Reuptake Inhibitors Does Not Affect Regrowth of Serotonin Axons Following Amphetamine Injury in the Mouse Forebrain.
Janowitz HN, Linden DJ. Janowitz HN, et al. eNeuro. 2024 Feb 14;11(2):ENEURO.0444-22.2023. doi: 10.1523/ENEURO.0444-22.2023. Print 2024 Feb. eNeuro. 2024. PMID: 38355299 Free PMC article. - Extracellular molecular signals shaping dendrite architecture during brain development.
Hamad MIK, Emerald BS, Kumar KK, Ibrahim MF, Ali BR, Bataineh MF. Hamad MIK, et al. Front Cell Dev Biol. 2023 Dec 7;11:1254589. doi: 10.3389/fcell.2023.1254589. eCollection 2023. Front Cell Dev Biol. 2023. PMID: 38155836 Free PMC article. Review. - Xenopus retinal ganglion cell axon extension is unaffected by 5-HT 1B/D receptor activation during visual system development.
Basakis P, Khaderi A, Lom B. Basakis P, et al. MicroPubl Biol. 2023 Dec 4;2023:10.17912/micropub.biology.001076. doi: 10.17912/micropub.biology.001076. eCollection 2023. MicroPubl Biol. 2023. PMID: 38116474 Free PMC article. - Spinal motoneurons respond aberrantly to serotonin in a rabbit model of cerebral palsy.
Reedich EJ, Genry LT, Steele PR, Mena Avila E, Dowaliby L, Drobyshevsky A, Manuel M, Quinlan KA. Reedich EJ, et al. J Physiol. 2023 Oct;601(19):4271-4289. doi: 10.1113/JP284803. Epub 2023 Aug 16. J Physiol. 2023. PMID: 37584461 Free PMC article. - Serotonin Receptors and Their Involvement in Melanization of Sensory Cells in Ciona intestinalis.
Mercurio S, Bozzo M, Pennati A, Candiani S, Pennati R. Mercurio S, et al. Cells. 2023 Apr 13;12(8):1150. doi: 10.3390/cells12081150. Cells. 2023. PMID: 37190059 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Miscellaneous