Complex regional influence of photoperiod on the nycthemeral functioning of the dorsal and median raphé serotoninergic system in the Syrian hamster

Abstract

The Syrian hamster (Mesocricetus auratus) is a widely used species for the study of biological clock synchronization and photoperiodism. The serotoninergic system arising from the median (MnR) and the dorsal raphé (DR) is a major actor in circadian clock synchronization. This serotoninergic system is also associated with functions and behaviours influenced by seasonal changes. The aim of the present study was to assess the influence of photoperiod on the daily functioning of the MnR and DR serotoninergic system. The morphology of both raphé nuclei was analysed in hamsters kept under long and short photoperiod by immunocytochemical detection of two markers of the serotoninergic system, serotonin and tryptophan hydroxylase (TPH, the rate-limiting enzyme of serotonin synthesis). The morphological analysis revealed a fairly complex morphological organization of the DR and MnR along their caudo-rostral extent. This morphological organisation was similar in the two photoperiods. However, quantification of several markers of serotonin (5-HT) synthesis in the DR and MnR revealed a time-dependent functioning of serotoninergic cells that was locally influenced by photoperiod. In particular, the significant daily variations of tph2-mRNA and TPH levels in the rostral MnR, and of the 5-HT/5-HIAA (5-hydroxyindoleacetic acid) ratio within the suprachiasmatic nuclei, were abolished under short photoperiod. The results are discussed with regard to the known physiological role of the serotoninergic system on the biological clock.

Advances in tryptophan hydroxylase‐2 gene expression regulation: New insights into serotonin–stress interaction and clinical implications

“…Notably, this daily rhythmic tph2 mRNA expression was correlated with the previous report of circadian variations in TPH protein level and 5‐HT synthesis in serotonergic neurons projecting to the hypothalamic suprachiasmatic nuclei (SCN) and the thalamic intergeniculate leaflets (IGL)—both are involved in the entrainment of the biological clock [Malek et al, 2005]. Similarly, it was demonstrated that tph2 mRNA and TPH protein levels in dorsal and MR display daily fluctuations in hamsters held in long photoperiod [Nexon et al, 2009].…”

“…In agreement with the GC regulation of tph2 gene expression, the circadian rhythmic tph2 expression is dependent on the daily fluctuation of glucocoticoids. In both rat and hamster, adrenalectomy led to a complete suppression of the daily rhythmic tph2 mRNA expression in raphe nucleus, while restoration of GC daily variations in adrenalectomized animals induced the tph2 mRNA rhythmic pattern de novo [Malek et al, 2007; Nexon et al, 2009]. These findings, along with the previously reported correlation between rhythmic TPH protein level and 5‐HT synthesis in neurons projecting to the SCN and IGL, strongly suggest that the fluctuation of TPH2 gene expression is closely related to the biological clock and the stress response.…”

Tryptophan hydroxylase-2: An emerging therapeutic target for stress disorders

“…Particularly, the daily rhythmic Tph2 mRNA expression in rat rhaphe was correlated with circadian variations in levels of TPH protein and 5-HT synthesis in serotonergic neurons projecting to the hypothalamic suprachiasmatic nuclei (SCN) and thalamic intergeniculate leaflets (IGL) – both are involved in the entrainment of the biological clock. Similarly, daily variation in Tph2 mRNA and TPH protein levels was also observed in hamster raphe [28]. In accordance with 5-HT regulation of circadian rhythm [29], these findings suggest a reciprocal interaction between TPH2 gene expression and the daily biological clock, which actually represents the adaptive response of the organism to the environmental LD cycle (or day/night transition).…”

“…Since GC is released upon activation of all types of stressors, GC regulation of TPH2 expression presumably contributes to the above-mentioned stressor regulation of TPH2 expression, and it underlies the daily rhythmic TPH2 expression, which is induced by the daily fluctuation of GC production [28, 42]. In both rat and hamster, adrenalectomy abolished the daily rhythmic tph2 expression in raphe nucleus, while restoration of GC daily variation in adrenalectomized animals induced a tph2 rhythmic pattern de novo [42, 43].…”

Vitamin D hormone regulates serotonin synthesis. Part 1: relevance for autism

“…This suggests that the inverse relationship between vitamin D concentrations and melatonin may be due to vitamin D-mediated transcriptional repression of TPH1. 6) TPH1 mRNA expression is lowest during the day and highest during the night, whereas TPH2 is highest in the day and lowest in the night (103)(104)(105). Together, all of this evidence points to a novel mechanism by which vitamin D transcriptionally represses TPH1 and activates TPH2, thereby inversely affecting serotonin production in peripheral tissues relative to production in the brain.…”