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Alterations of Expression of the Serotonin 5-HT4 Receptor in Brain Disorders - PubMed

  • ️Mon Jan 01 2018

Review

Alterations of Expression of the Serotonin 5-HT4 Receptor in Brain Disorders

Heike Rebholz et al. Int J Mol Sci. 2018.

Abstract

The serotonin 4 receptor, 5-HT₄R, represents one of seven different serotonin receptor families and is implicated in a variety of physiological functions and their pathophysiological variants, such as mood and depression or anxiety, food intake and obesity or anorexia, or memory and memory loss in Alzheimer's disease. Its central nervous system expression pattern in the forebrain, in particular in caudate putamen, the hippocampus and to lesser extent in the cortex, predispose it for a role in executive function and reward-related actions. In rodents, regional overexpression or knockdown in the prefrontal cortex or the nucleus accumbens of 5-HT₄R was shown to impact mood and depression-like phenotypes, food intake and hypophagia; however, whether expression changes are causally involved in the etiology of such disorders is not clear. In this context, more data are emerging, especially based on PET technology and the use of ligand tracers that demonstrate altered 5-HT₄R expression in brain disorders in humans, confirming data stemming from post-mortem tissue and preclinical animal models. In this review, we would like to present the current knowledge of 5-HT₄R expression in brain regions relevant to mood/depression, reward and executive function with a focus on 5-HT₄R expression changes in brain disorders or caused by drug treatment, at both the transcript and protein levels.

Keywords: 5-HT 4 receptor; 5-HT4R; Alzheimer’s disease; Parkinson’s disease; cognition; depression; expression; mood disorder; serotonin.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1

Alignment of C-termini of isoforms found in human tissue: green: leucine 358, the last amino acid common to all variants. For the c isoform, a short and a long one were described. Yellow: S/T cluster necessary for b-arrestin dependent receptor endocytosis.

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References

    1. Palacios J.M. Serotonin receptors in brain revisited. Brain Res. 1645 doi: 10.1016/j.brainres.2015.12.042. - DOI - PubMed
    1. Riad M., Garcia S., Watkins K.C., Jodoin N., Doucet E., Langlois X., el Mestikawy S., Hamon M., Descarries L. Somatodendritic localization of 5-ht1a and preterminal axonal localization of 5-ht1b serotonin receptors in adult rat brain. J. Comp. Neurol. 2000;417:181–194. doi: 10.1002/(SICI)1096-9861(20000207)417:2<181::AID-CNE4>3.0.CO;2-A. - DOI - PubMed
    1. Lerer B., Macciardi F., Segman R.H., Adolfsson R., Blackwood D., Blairy S., Del Favero J., Dikeos D.G., Kaneva R., Lilli R., et al. Variability of 5-ht2c receptor cys23ser polymorphism among european populations and vulnerability to affective disorder. Mol. Psychiatry. 2001;6:579–585. doi: 10.1038/sj.mp.4000883. - DOI - PubMed
    1. Tecott L.H., Sun L.M., Akana S.F., Strack A.M., Lowenstein D.H., Dallman M.F., Julius D. Eating disorder and epilepsy in mice lacking 5-ht2c serotonin receptors. Nature. 1995;374:542–546. doi: 10.1038/374542a0. - DOI - PubMed
    1. Vollenweider F.X., Kometer M. The neurobiology of psychedelic drugs: Implications for the treatment of mood disorders. Nat. Rev. Neurosci. 2010;11:642–651. doi: 10.1038/nrn2884. - DOI - PubMed

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