Colocalized neurotransmitters in the hindbrain cooperate in adaptation to chronic hypernatremia

Rita Matuska,Dorina Guba,Bibiana Török,Peter Varnai,Zsuzsanna E Tóth,Rege Sugárka Papp,Katalin Könczöl,Dóra Zelena,Máté Durst

doi:10.1007/s00429-020-02049-y

Abstract

Chronic hypernatremia activates the central osmoregulatory mechanisms and inhibits the function of the hypothalamic–pituitary–adrenal (HPA) axis. Noradrenaline (NE) release into the periventricular anteroventral third ventricle region (AV3V), the supraoptic (SON) and hypothalamic paraventricular nuclei (PVN) from efferents of the caudal ventrolateral (cVLM) and dorsomedial (cDMM) medulla has been shown to be essential for the hypernatremia-evoked responses and for the HPA response to acute restraint. Notably, the medullary NE cell groups highly coexpress prolactin-releasing peptide (PrRP) and nesfatin-1/NUCB2 (nesfatin), therefore, we assumed they contributed to the reactions to chronic hypernatremia. To investigate this, we compared two models: homozygous Brattleboro rats with hereditary diabetes insipidus (DI) and Wistar rats subjected to chronic high salt solution (HS) intake. HS rats had higher plasma osmolality than DI rats. PrRP and nesfatin mRNA levels were higher in both models, in both medullary regions compared to controls. Elevated basal tyrosine hydroxylase (TH) expression and impaired restraint-induced TH, PrRP and nesfatin expression elevations in the cVLM were, however, detected only in HS, but not in DI rats. Simultaneously, only HS rats exhibited classical signs of chronic stress and severely blunted hormonal reactions to acute restraint. Data suggest that HPA axis responsiveness to restraint depends on the type of hypernatremia, and on NE capacity in the cVLM. Additionally, NE and PrRP signalization primarily of medullary origin is increased in the SON, PVN and AV3V in HS rats. This suggests a cooperative action in the adaptation responses and designates the AV3V as a new site for PrRP’s action in hypernatremia.

Highlights

Homeostatic regulation of plasma osmolality (275–290 mOsm/kg) is vital
Based on the above facts, we addressed the following questions: 1, whether the level of the stress caused by chronic hypernatremia may depend on the type of hypernatremia; 2, whether the different types of chronic hypernatremia affect the responsiveness to acute restraint differentially; and 3, whether the expression of tyrosine hydroxylase (TH), prolactin-releasing peptide (PrRP) and nesfatin in the caudal ventrolateral (cVLM) and dorsomedial (cDMM) and cVLM reflects the actual sensitivity of the HPA axis to acute restraint under chronic hypernatremic conditions
Contribution of nesfatin acting by autocrine/ paracrine manner within the cVLM and cDMM is suggested

Summary

Introduction

Homeostatic regulation of plasma osmolality (275–290 mOsm/kg) is vital. Elevated osmolality develops primarily based on elevated extracellular [Na+] level known as hypernatremia. NE is an essential transmitter for stimulating areas in the hypothalamus that govern the neuroendocrine, autonomic and behavioral responses for hypernatremia (Day 1989; Tanaka et al 1997; Huang et al 2000; Bourque 2008; Pedrino et al 2012; da Silva et al 2013; Sawchenko and Swanson 1981; Pacak et al 1995) These areas receive their NE innervation primarily from the neurons of the A1, A2 cell groups and include the paraventricular (PVN) and supraoptic (SON) nuclei as well as the periventricular anteroventral third ventricle region (AV3V). The latter comprises the organum vasculosum laminae terminalis (OVLT), the median preoptic nucleus (MnPO) and the preoptic and anteroventral periventricular nuclei (Bourque 2008; Menani et al 2014)

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