Rescue of Vasopressin Synthesis in Magnocellular Neurons of the Supraoptic Nucleus Normalises Acute Stress-Induced Adrenocorticotropin Secretion and Unmasks an Effect on Social Behaviour in Male Vasopressin-Deficient Brattleboro Rats.

Bibiána Török,Dóra Zelena,Mario Engelmann,Anna Fodor,Szilamér Ferenczi,Katalin Könczöl,Krisztina J Kovács,Zsuzsanna E Tóth,Imre Farkas,Diána Balázsfi,Kornél Demeter,Judith Camats Perna,Péter Csikota,József Haller

doi:10.3390/ijms23031357

Abstract

The relevance of vasopressin (AVP) of magnocellular origin to the regulation of the endocrine stress axis and related behaviour is still under discussion. We aimed to obtain deeper insight into this process. To rescue magnocellular AVP synthesis, a vasopressin-containing adeno-associated virus vector (AVP-AAV) was injected into the supraoptic nucleus (SON) of AVP-deficient Brattleboro rats (di/di). We compared +/+, di/di, and AVP-AAV treated di/di male rats. The AVP-AAV treatment rescued the AVP synthesis in the SON both morphologically and functionally. It also rescued the peak of adrenocorticotropin release triggered by immune and metabolic challenges without affecting corticosterone levels. The elevated corticotropin-releasing hormone receptor 1 mRNA levels in the anterior pituitary of di/di-rats were diminished by the AVP-AAV-treatment. The altered c-Fos synthesis in di/di-rats in response to a metabolic stressor was normalised by AVP-AAV in both the SON and medial amygdala (MeA), but not in the central and basolateral amygdala or lateral hypothalamus. In vitro electrophysiological recordings showed an AVP-induced inhibition of MeA neurons that was prevented by picrotoxin administration, supporting the possible regulatory role of AVP originating in the SON. A memory deficit in the novel object recognition test seen in di/di animals remained unaffected by AVP-AAV treatment. Interestingly, although di/di rats show intact social investigation and aggression, the SON AVP-AAV treatment resulted in an alteration of these social behaviours. AVP released from the magnocellular SON neurons may stimulate adrenocorticotropin secretion in response to defined stressors and might participate in the fine-tuning of social behaviour with a possible contribution from the MeA.

Highlights

The hypothalamic-pituitary-adrenocortical (HPA) axis is the major endocrine system involved in stress adaptation of the mammalian organism [1]
Both the proopiomelanocortin (POMC) and vasopressin 1b receptor (V1b-R) mRNA levels did not differ between the groups (Figure 2A,B)
Corticotropin-releasing hormone receptor 1 (CRH-R1) mRNA was enhanced in di/di compared to +/+, whereas di/di-AVP animals did not differ from +/+ (Figure 2C; F(2,18) = 7.993, p = 0.003)

Summary

Introduction

The hypothalamic-pituitary-adrenocortical (HPA) axis is the major endocrine system involved in stress adaptation of the mammalian organism [1]. The isolation and characterization of the corticotropin-releasing hormone (CRH) in the early 1980s put the function of AVP as the regulator of HPA axis activity into a new perspective [4]. Subsequent studies revealed that in adult animals, AVP of hypothalamic origin, co-synthesized with CRH in the parvocellular neurons of the paraventricular nucleus of the hypothalamus (PVN), reaches the anterior pituitary through the long portal vessels and acts synergistically with. It is of note that, in the mammalian brain, the vast majority of AVP is synthesized in magnocellular hypothalamic neurons located both in the PVN and in the supraoptic nucleus (SON). Several authors suggested mechanisms by which AVP of magnocellular origin might contribute to HPA axis regulation [5,6,7], previous approaches to test this hypothesis by employing different manipulations (elimination or rescue of magnocellular AVP synthesis and application of defined stressors) and analysis techniques (c-Fos immunohistochemistry, electrophysiology, microdialysis, etc.) failed to provide conclusive results [2,5]

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