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

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.

Metabolic effects of vasopressin in pathophysiology of diabetic kidney disease

“…Presence of V1aR in MD cells was demonstrated in the mouse species only, whereas localization of the receptor in rat and human kidney failed to confirm this result ( 16 ). Despite potential interspecies differences in V1aR-dependent regulation of renin release, extra-renal stimulating effects of VP on RAAS activity such as enhanced ACTH or adrenal hormone secretion were extensively documented in rodent and human species ( 28 , 29 , 38 , 40 , 41 , 64 ).…”

Vasopressin as Possible Treatment Option in Autism Spectrum Disorder

“…Thus, they have diabetes insipidus and urinate excessively due to missing the peripheral VP hormone. Moreover, they also exhibit behavioral alterations in social behavior, cognition [159,160] and stress response [159,[161][162][163], making them an ideal model for SCZ [164][165][166]. However, during early development, they can serve as an ASD model as well.…”

“…The role of VP in aggression, a specific social behavior often observable in ASD patients, is brain-area-specific as its release in the LS facilitates, while BNST decreases, intermale aggression in rats [285]. Moreover, a fine balance exists between different areas, as SON replacement of VP in Brattleboro rats led to an increase in friendly interactions, which were originally normal in KO animals [159]. The VP immunoreactivity in both the LS and BNST is sexually dimorphic, and, in males, it is dependent on neonatal testosterone levels, later shaping aggressive behavior in mice [286].…”

Estradiol and Estrogen-like Alternative Therapies in Use: The Importance of the Selective and Non-Classical Actions

“…On the contrary, in males, the lack of testosterone after orchidectomy decreased the body weight without changes in fat content, most probably due to the lack of its anabolic effect on protein synthesis [326]. [327]). (A) The body weight difference showed significant sex difference (F (1,34) = 39.5, p < 0.01) as well as sex * OCX-OXV interaction (F (1,34) = 15.0, p < 0.01), with a decrease in males and an elevation in females.…”

“…Figure10. Effect of removal of sex hormones on the body composition in 4-month-old C57/Bl6 mice measured by magnetic resonance imaging (MRI) in the Metabolic Laboratory of the Institute of Experimental Medicine, Budapest, Hungary, 4 weeks after removal of the hormones (orchidectomy (OCX) in males and ovariectomy (OVX) in females under ketamine-xylazin anesthesia[327]). (A) The body weight difference showed significant sex difference (F (1,34) = 39.5, p < 0.01) as well as sex * OCX-OXV interaction (F (1,34) = 15.0, p < 0.01), with a decrease in males and an elevation in females.…”