Melanocortin receptor 3 and 4 mRNA expression in the adult female Syrian hamster brain.

Melanocortin 3 receptors (MC3R) and melanocortin 4 receptors (MC4R) are vital in regulating a variety of functions across many species. For example, the dysregulation of these receptors results in obesity and dysfunction in sexual behaviors. Only a handful of studies have mapped the expression of MC3R and MC4R mRNA across the central nervous system, with the primary focus on mice and rats. Because Syrian hamsters are valuable models for functions regulated by melanocortin receptors, our current study maps the distribution of MC3R and MC4R mRNA in the Syrian hamster telencephalon, diencephalon, and midbrain using RNAscope. We found that the expression of MC3R mRNA was lowest in the telencephalon and greatest in the diencephalon, whereas the expression of MC4R mRNA was greatest in the midbrain. A comparison of these findings to previous studies found that MC3R and MC4R expression is similar in some brain regions across species and divergent in others. In addition, our study identifies novel brain regions for the expression of MC3Rs and MC4Rs, and identifies cells that co-express bothMC3 and MC4 receptors within certain brain regions.

Aggression Results in the Phosphorylation of ERK1/2 in the Nucleus Accumbens and the Dephosphorylation of mTOR in the Medial Prefrontal Cortex in Female Syrian Hamsters.

Like many social behaviors, aggression can be rewarding, leading to behavioral plasticity. One outcome of reward-induced aggression is the long-term increase in the speed in which future aggression-based encounters is initiated. This form of aggression impacts dendritic structure and excitatory synaptic neurotransmission in the nucleus accumbens, a brain region well known to regulate motivated behaviors. Yet, little is known about the intracellular signaling mechanisms that drive these structural/functional changes and long-term changes in aggressive behavior. This study set out to further elucidate the intracellular signaling mechanisms regulating the plasticity in neurophysiology and behavior that underlie the rewarding consequences of aggressive interactions. Female Syrian hamsters experienced zero, two or five aggressive interactions and the phosphorylation of proteins in reward-associated regions was analyzed. We report that aggressive interactions result in a transient increase in the phosphorylation of extracellular-signal related kinase 1/2 (ERK1/2) in the nucleus accumbens. We also report that aggressive interactions result in a transient decrease in the phosphorylation of mammalian target of rapamycin (mTOR) in the medial prefrontal cortex, a major input structure to the nucleus accumbens. Thus, this study identifies ERK1/2 and mTOR as potential signaling pathways for regulating the long-term rewarding consequences of aggressive interactions. Furthermore, the recruitment profile of the ERK1/2 and the mTOR pathways are distinct in different brain regions.

Cesarean birth elicits long-term effects on vasopressin and oxytocin neurons in the hypothalamic paraventricular nucleus of mice.

Birth is an extraordinary event for placental mammals and occurs at a time when key developmental processes are shaping the brain. Remarkably, little is known about the contributions of birth to brain development and whether birth mode (vaginal vs. Cesarean) alters neurodevelopmental trajectories. We previously reported that Cesarean birth reduces vasopressin (VP) neuron number in the hypothalamic paraventricular nucleus (PVN) of mice at weaning. In this study, we investigated whether this effect extends to adulthood and whether birth mode affects oxytocin (OT) neurons, which are another prominent population in the PVN. We found that Cesarean-born adults had fewer VP neurons in the PVN, specifically in magnocellular regions. Interestingly, these regions also had more dying cells following a Cesarean birth, suggesting that cell death may be the underlying mechanism. The PVN of Cesarean-born adults also had smaller VP neuron somas and reduced VP efferent projections. Additionally, Cesarean-born mice showed fewer and smaller OT neurons in the PVN, but these effects were less robust than for VP neurons. We also examined VP and OT neuron number in the supraoptic and suprachiasmatic nuclei but found no effect of birth mode in these regions. Thus, Cesarean birth causes long-term effects on the VP and, to a lesser extent, OT systems in the PVN, suggesting that this region is particularly sensitive to the effects of birth mode. Our findings may help explain the social deficits reported for Cesarean-born mice, and are also of clinical significance given the widespread practice of Cesarean births across the world.

Birth elicits a conserved neuroendocrine response with implications for perinatal osmoregulation and neuronal cell death.

Long-standing clinical findings report a dramatic surge of vasopressin in umbilical cord blood of the human neonate, but the neural underpinnings and function(s) of this phenomenon remain obscure. We studied neural activation in perinatal mice and rats, and found that birth triggers activation of the suprachiasmatic, supraoptic, and paraventricular nuclei of the hypothalamus. This was seen whether mice were born vaginally or via Cesarean section (C-section), and when birth timing was experimentally manipulated. Neuronal phenotyping showed that the activated neurons were predominantly vasopressinergic, and vasopressin mRNA increased fivefold in the hypothalamus during the 2-3 days before birth. Copeptin, a surrogate marker of vasopressin, was elevated 30-to 50-fold in plasma of perinatal mice, with higher levels after a vaginal than a C-section birth. We also found an acute decrease in plasma osmolality after a vaginal, but not C-section birth, suggesting that the difference in vasopressin release between birth modes is functionally meaningful. When vasopressin was administered centrally to newborns, we found an ~ 50% reduction in neuronal cell death in specific brain areas. Collectively, our results identify a conserved neuroendocrine response to birth that is sensitive to birth mode, and influences peripheral physiology and neurodevelopment.