Substratos neurais envolvidos no efeito da interação social sobre a sincronização fótica do núcleo supraquiasmático e seus eferentes de camundongos

Abstract

Social interaction is among the non-photic temporal cues capable of altering the neuronal activity of the suprachiasmatic nucleus (SCN), which leads to changes in activity and temperature light and dark (LD)-entrained rhythms. The present study aimed to identify the neural substrates involved with the effect of social interaction on the SCN photic synchronization, as well as on the SCN-efferents involved with thermoregulation and alertness. For this, adult C57Bl6/J mice in the presence of social interaction among their conspecifics were kept in groups of 3-4 animals (Grouped-housed or GH) or in the absence of this temporal cue, isolated in their boxes (Single-housed or GH) for 28 days under 12:12 h LD cycle (CEUA/UFMG nº 11/2018). At the end of this protocol, animals were transcardially perfused for fixation of the brains, which were processed to identify neurons labeled for c-FOS (protein indicator of neuronal activity), for the enzyme tyrosine-hydroxylase (marker of catecholaminergic neurons), for vasopressin (AVP) and for the vasoactive-intestinal polypeptide (VIP) by immunohistochemistry. Another group of GH or SH animals was euthanized by decapitation. From these animals, brains were obtained for microdissection of the SCN and nucleus accumbens (NAcc), where serotonin (5-HT) and dopamine (DA) and their metabolites, 5-hydroxyindoleacetic acid (5-HIAA) and 3,4-dihydroxyphenylacetic acid (DOPAC), respectively, where measured by HPLC. SH animals showed a decrease in the percentage of vasopressinergic neurons expressing c-Fos in the SCN at zeitgeber time (ZT) 2, while the expression of VIP was similar to that observed in GH animals, indicating that social interaction selectively activates vasopressinergic neurons at the beginning of the light phase. The number of c-Fos immunoreactive (ir) neurons in the preoptic area (POA) was similar in GH and SH animals. On the other hand, social isolation was able to reduce the number of vasopressinergic neurons that express c-Fos in the paraventricular nucleus of the hypothalamus (PVN) at both times studied, ZT2 and ZT14. Added to the result that SH animals showed a reduction in the number of TH positive neurons that express c-Fos in the locus coeruleus (LC), we can infer that social interaction activates circuits involved with alertness/wakefulness and stress responses (PVN-LC). Furthermore, we observed an increase in the 5-HIAA/5HT and DOPAC/DA ratio in the SCN of SH animals in the ZT2, suggesting an increased turnover of 5- HT and DA at the beginning of the light phase. In NAcc, these ratios were high in SH animals in ZT14, which is possibly involved with the increase in alertness at the beginning of the dark phase. We conclude that vasopressinergic neurons in the SCN participate in the effect of social interaction in maintaining SCN neuronal activity at the beginning of the light phase. A reduction in this activity observed during social isolation seems to compromise the activity of SCN efferents involved with alertness; social behavior; reward and stress. Furthermore, the presence of social interaction ensures adequate serotonergic and dopaminergic tone in the SCN, which may be involved with the photic response of this nucleus during synchronization to the light and dark cycle. Therefore, the establishment and maintenance of social bonds are important not only for the maintenance of health, quality of life and survival, but also for sustaining the proper functioning of the central clock.