Hormonal Response
hormonal response
Role of Oxytocin in regulating microglia functions to prevent brain damage of the developing brain
Every year, 30 million infants worldwide are delivered after intra-uterine growth restriction (IUGR) and 15 million are born preterm. These two conditions are the leading causes of ante/perinatal stress and brain injury responsible for neurocognitive and behavioral disorders in more than 9 million children each year. Both prematurity and IUGR are associated with perinatal systemic inflammation, a key factor associated with neuroinflammation and identified to be the best predictor of subsequent neurological impairments. Most of pharmacological candidates have failed to demonstrate any beneficial effect to prevent perinatal brain damage. In contrast, environmental enrichment based on developmental care, skin-to-skin contact and vocal/music intervention appears to confer positive effects on brain structure and function. However, mechanisms underlying these effects remain unknown. There is strong evidence that an adverse environment during pregnancy and the perinatal period can influence hormonal responses of the newborn with long-lasting neurobehavioral consequences in infancy and adulthood. Excessive cortisol release in response to perinatal stress induces pro-inflammatory and brain-programming effects. These deleterious effects are known to be balanced by Oxytocin (OT), a neuropeptide playing a key role during the perinatal period and parturition, in social behavior and regulating the central inflammatory response to injury in the adult brain. Using a rodent model of IUGR associated with perinatal brain damage, we recently reported that Carbetocin, a brain permeable long-lasting OT receptor (OTR) agonist, was associated with a significant reduction of activated microglia, the primary immune cells of the brain. Moreover this reduced microglia reactivity was associated to a long-term neuroprotection. These findings make OT a promising candidate for neonatal neuroprotection through neuroinflammation regulation. However, the causality between the endogenous OT and central inflammation response to injury has not been established and will be further studied by the lab.
Long-term effects of diet-induced obesity on gut-brain communication
Rapid communication between the gut and the brain about recently consumed nutrients is critical for regulating food intake and maintaining energy homeostasis. We have shown that the infusion of nutrients directly into the gastrointestinal tract rapidly inhibits hunger-promoting AgRP neurons in the arcuate nucleus of the hypothalamus and suppresses subsequent feeding. The mechanism of this inhibition appears to be dependent upon macronutrient content, and can be recapitulated by a several hormones secreted in the gut in response to nutrient ingestion. In high-fat diet-induced obese mice, the response of AgRP neurons to nutrient-related stimuli are broadly attenuated. This attenuation is largely irreversible following weight loss and may represent a mechanism underlying difficulty with weight loss and propensity for weight regain in obesity.