Neuroendocrinology applied to rabbit breeding

Successful rabbit production relies heavily on the use of adequate practices that enhance specific aspects of reproduction, such as mating, ovulation and lactation. Regardless of the type of production unit or strain of rabbits used, these processes rely on a complex chain of neuroendocrine steps that include particular hormones, peripheral stimuli and activation of discrete brain regions. Such is the case, for instance, of reflex ovulation, which occurs in response to copulation but is inhibited throughout lactation. Little is known about the mechanisms mediating lactational anoestrus and the restoration of oestrus following the cancellation of a single suckling episode (biostimulation). Nevertheless, the latter procedure (adopted worldwide to accelerate reproduction) has unwanted consequences for the doe and her litter. After successive episodes of biostimulation, the former shows a loss of fertility and body mass. In the kits, alterations are observed in their neuroendocrine response to mildly aversive stimulation in adulthood, as well as reductions in sexual behaviour. In addition to milk intake, a good nest is essential for normal litter growth and development. If this is not available, or if it deteriorates, rabbit caretakers can easily (re) build one from hair sheared off other rabbits or using synthetic material. Lactating does will nurse equally well their own or ‘alien’ young, placed inside the nest. It is crucial to have a minimum of six suckling kits in the nest, as the doe relies on this stimulation to maintain a normal nursing behaviour, i.e., only once a day throughout lactation. Recent work is revealing the similarities and differences in the responsiveness to mating among oestrous, lactating and biostimulated does. The relevance of these findings for the likelihood of reflex ovulation and the additional contribution of factors contained in the semen warrant more in-depth research. New insights on these issues, essential to reproductive neuroendocrinology, can emerge by fostering a richer interaction between academic laboratories and rabbit production settings worldwide.

Excitatory Impact of Dental Occlusion on Dorsal Motor Nucleus of Vagus

Neurons in the trigeminal mesencephalic nucleus (Vme) have axons that branch peripherally to innervate the orofacial region and project centrally to several motor nuclei in brainstem. The dorsal motor nucleus of vagus nerve (DMV) resides in the brainstem and takes a role in visceral motor function such as pancreatic exocrine secretion. The present study aimed to demonstrate the presence of Vme–DMV circuit, activation of which would elicit a trigeminal neuroendocrine response. A masticatory dysfunctional animal model termed unilateral anterior crossbite (UAC) model created by disturbing the dental occlusion was used. Cholera toxin B subunit (CTb) was injected into the inferior alveolar nerve of rats to help identify the central axon terminals of Vme neurons around the choline acetyltransferase (ChAT) positive motor neurons in the DMV. The level of vesicular glutamate transporter 1 (VGLUT1) expressed in DMV, the level of acetylcholinesterase (AChE) expressed in pancreas, the level of glucagon and insulin expression in islets and serum, and the blood glucose level were detected and compared between UAC and the age matched sham-operation control mice. Data indicated that compared with the controls, there were more CTb/VGLUT1 double labeled axon endings around the ChAT positive neurons in the DMV of UAC groups. Mice in UAC group expressed a higher VGLUT1 protein level in DMV, AChE protein level in pancreas, glucagon and insulin level in islet and serum, and higher postprandial blood glucose level, but lower fasting blood glucose level. All these were reversed at 15-weeks when UAC cessation was performed from 11-weeks (all, P < 0.05). Our findings demonstrated Vme–DMV circuit via which the aberrant occlusion elicited a trigeminal neuroendocrine response such as alteration in the postprandial blood glucose level. Dental occlusion is proposed as a potential therapeutic target for reversing the increased postprandial glucose level.

Influences of Stress and Sex on the Paraventricular Thalamus: Implications for Motivated Behavior

The paraventricular nucleus of the thalamus (PVT) is a critical neural hub for the regulation of a variety of motivated behaviors, integrating stress and reward information from environmental stimuli to guide discrete behaviors via several limbic projections. Neurons in the PVT are activated by acute and chronic stressors, however several roles of the PVT in behavior modulation emerge only following repeated stress exposure, pointing to a role for hypothalamic pituitary adrenal (HPA) axis modulation of PVT function. Further, there may be a reciprocal relationship between the PVT and HPA axis in which chronic stress-induced recruitment of the PVT elicits an additional role for the PVT to regulate motivated behavior by modulating HPA physiology and thus the neuroendocrine response to stress itself. This complex interaction may make the PVT and its role in influencing motivated behavior particularly susceptible to chronic stress-induced plasticity in the PVT, especially in females who display increased susceptibility to stress-induced maladaptive behaviors associated with neuropsychiatric diseases. Though literature is describing the sex-specific effects of acute and chronic stress exposure on HPA axis activation and motivated behaviors, the impact of sex on the role of the PVT in modulating the behavioral and neuroendocrine response to stress is less well established. Here, we review what is currently known regarding the acute and chronic stress-induced activation and behavioral role of the PVT in male and female rodents. We further explore stress hormone and neuropeptide signaling mechanisms by which the HPA axis and PVT interact and discuss the implications for sex-dependent effects of chronic stress on the PVT’s role in motivated behaviors.

Neuroendocrine Response to Exogenous Ghrelin Administration, Combined With Alcohol, in Heavy-Drinking Individuals: Findings From a Randomized, Double-Blind, Placebo-Controlled Human Laboratory Study

Background Accumulating evidence has established a role for the orexigenic hormone ghrelin in alcohol-seeking behaviors. Accordingly, the ghrelin system may represent a potential pharmacotherapeutic target for alcohol use disorder. Ghrelin modulates several neuroendocrine pathways, such as appetitive, metabolic, and stress-related hormones, which are particularly relevant in the context of alcohol use. The goal of the present study was to provide a comprehensive assessment of neuroendocrine response to exogenous ghrelin administration, combined with alcohol, in heavy-drinking individuals. Methods This was a randomized, crossover, double-blind, placebo-controlled human laboratory study, which included 2 experimental alcohol administration paradigms: i.v. alcohol self-administration and i.v. alcohol clamp. Each paradigm consisted of 2 counterbalanced sessions of i.v. ghrelin or placebo administration. Repeated blood samples were collected during each session, and peripheral concentrations of the following hormones were measured: leptin, glucagon-like peptide-1, pancreatic polypeptide, gastric inhibitory peptide, insulin, insulin-like growth factor-1, cortisol, prolactin, and aldosterone. Results Despite some statistical differences, findings were consistent across the 2 alcohol administration paradigms: i.v. ghrelin, compared to placebo, increased blood concentrations of glucagon-like peptide-1, pancreatic polypeptide, cortisol, and prolactin, both acutely and during the whole session. Lower levels of leptin and higher levels of aldosterone were also found during the ghrelin vs placebo session. Conclusion These findings, gathered from a clinically relevant sample of heavy-drinking individuals with alcohol use disorder, provide a deeper insight into the complex interplay between ghrelin and appetitive, metabolic, and stress-related neuroendocrine pathways in the context of alcohol use.

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.