Monoaminergic control of vasopressin and VIP expression in the mouse suprachiasmatic nucleus

Abstract

We studied the effects of serotonin and noradrenaline on the expression of arginine-vasopressin (AVP) and vasoactive intestinal peptide (VIP) in the suprachiasmatic nucleus (SCN). We used transgenic Tg8 mice knockout for the MAO-A (monoamine oxidase A) gene, which are characterized by increased amounts of serotonin and noradrenaline in brain compared to wild-type mice (C3H). The MAO-A deficiency caused an increase in AVP and VIP expression (determined by immunohistochemistry, enzyme immunoassay, and in situ hybridization) compared to C3H mice. The number of peptidergic neurons was also increased. Inhibiting serotonin or noradrenaline synthesis in Tg8 mice by the administration of parachlorophenylalanine or alpha-methylparatyrosine, respectively, the amounts of AVP, VIP and their mRNAs were decreased, but not the number of peptidergic neurons. This study indicates that serotonin and noradrenaline stimulate AVP and VIP expression, and could participate in the differentiation of the neurochemical phenotype in the mouse SCN.

Noradrenaline Induces Clock Gene Per1 mRNA Expression in C6 Glioma Cells Through β2-Adrenergic Receptor Coupled With Protein Kinase A – cAMP Response Element Binding Protein (PKA–CREB) and Src-Tyrosine Kinase – Glycogen Synthase Kinase-3β (Src–GSK-3β)

“…Semba et al (14) demonstrated that NA levels in rat SCN are high during periods of light and low during periods of darkness, pointing to circadian oscillation of NA levels. Moreover, NA might modulate SCN circadian rhythms by regulating expression of arginine-vasopressin and vasoactive intestinal peptides, substances hypothesized to participate in control of circadian rhythms (15). In addition to the SCN, reports also have demonstrated that NA generates circadian-clock oscillation in peripheral organs and cells (16,17).…”

Postnatal regulation by monoamines of vasopressin expression in the neuroendocrine hypothalamus of MAO‐A‐deficient mice

“…In Tg8 mice, MAO‐A deficiency is correlated with an increase in brain 5‐HT and NA concentrations that is particularly marked in the SCN (Vacher et al ., 2003). Suprachiasmatic levels of AVP peptide and mRNA were higher in Tg8 than in C3H mice, suggesting a positive effect of monoamines on AVP expression at P11 in this nucleus.…”

“…Surprisingly, injections of pCPA to Tg8 mice induced an increase in AVP contents in the SCN, indicating a negative control of 5‐HT on AVP expression at P11. In the light of our previous data, which suggest a stimulatory effect of 5‐HT on AVP expression in the adult mouse SCN (Vacher et al ., 2003; Fig. 4A), this result reveals a differential sensitivity of AVP neurons to monoamines with age in mouse.…”

“…Such a differential age‐related effect of 5‐HT on peptide expression has been previously demonstrated for VIP in the rodent SCN. Indeed, after a 3 days of treatment with pCPA, VIP mRNA contents in the SCN are increased in rat fetuses (Ugrumov et al ., 1994a), decreased in adult rats and mice (Kawakami et al ., 1994, 1995; Vacher et al ., 2003) and not modified in 11‐day‐old rats (Ugrumov et al ., 1994a,c). This could be due to the maturation state of the synapses between serotonergic fibres and peptide neurons, and notably the 5‐HT receptor subtypes expressed at the AVP or VIP neuron membrane.…”

“…Indeed, noradrenergic projections preferentially innervate the PVN and the SON (Cunningham & Sawchenko, 1988), whereas the SCN is the main target for the serotonergic afferents (Hökfelt et al ., 1978). The use of a transgenic mouse model (Tg8) of permanent and specific overexposure to NA and 5‐HT in the brain due to the inactivation of the gene encoding the monoamine oxidase A (Cases et al ., 1995) allowed us to demonstrate a stimulating action of both NA and 5‐HT on AVP expression in the SCN (Vacher et al ., 2003), the PVN and the SON (Vacher et al ., 2002) in the adult mouse. Moreover, these studies strongly indicated an irreversible influence of NA and/or 5‐HT on the vasopressinergic phenotype differentiation in the hypothalamus.…”