Hypothalamic Neuropeptide Brain Protection: Focus on Oxytocin

Abstract

Oxytocin (OXT) is hypothalamic neuropeptide synthetized in the brain by magnocellular and parvo cellular neurons of the paraventricular (PVN), supraoptic (SON) and accessory nuclei (AN) of the hypothalamus. OXT acts in the central and peripheral nervous systems via G-protein-coupled receptors. The classical physiological functions of OXT are uterine contractions, the milk ejection reflex during lactation, penile erection and sexual arousal, but recent studies have demonstrated that OXT may have anti-inflammatory and anti-oxidant properties and regulate immune and anti-inflammatory responses. In the pathogenesis of various neurodegenerative diseases, microglia are present in an active form and release high levels of pro-inflammatory cytokines and chemokines that are implicated in the process of neural injury. A promising treatment for neurodegenerative diseases involves new therapeutic approaches targeting activated microglia. Recent studies have reported that OXT exerts neuroprotective effects through the inhibition of production of pro-inflammatory mediators, and in the development of correct neural circuitry. The focus of this review is to attribute a new important role of OXT in neuroprotection through the microglia–OXT interaction of immature and adult brains. In addition, we analyzed the strategies that could enhance the delivery of OXT in the brain and amplify its positive effects.

Oxytocin and Bone: Review and Perspectives

“…A systematic review of the effects of OT treatment in frontotemporal dementia reports an improvement in cognition and behavioral symptoms with a good tolerance [58]. Recent studies suggest neuroprotective effects of OT through the inhibition of the production of pro-inflammatory mediators [59]. Moreover, recent data point out the potential beneficial action of OT in vascular dementia, requiring further studies [42].…”

Altered environmental perception by parental stress and depression vulnerability: impact on mothers and offspring

“…In agreement, we observed that TNF levels were higher in depressive-like Kyoto dams in comparison with Wistar. However, there is also a large number of studies reporting that oxytocin reduces TNF production, inducing an anti-inflammatory state 54 . However, the mechanisms involved are elusive and in vitro results seem to indicate that oxytocin does not directly regulate TNF 54 .…”

“…However, there is also a large number of studies reporting that oxytocin reduces TNF production, inducing an anti-inflammatory state 54 . However, the mechanisms involved are elusive and in vitro results seem to indicate that oxytocin does not directly regulate TNF 54 . As such, it is possible that the higher TNF levels observed are constitutive in Kyoto dams, and do not seem to respond to increased oxytocin levels.…”

Targeting the Oxytocinergic System: A Possible Pharmacological Strategy for the Treatment of Inflammation Occurring in Different Chronic Diseases

“…In two different in vivo models of perinatal inflammation, administration of a selective agonist of the oxytocin receptor, carbetocin, induced a significant reduction of microglial morphological changes related to reactivity, as well as preventing the up-regulation of proinflammatory markers (including IL-6, IL-1β, TNF-α, and iNOS) and ameliorating the myelinization, which was seen both at histological and imaging examinations, ultimately improving performance at behavioral testing [ 71 ]. Therefore, the agonism to the oxytocin receptor, mediated by either the endogenous or an exogenous molecule, could exert anti-neuroinflammatory properties that could be neuroprotective in the developing brain that has been injured perinatally [ 72 , 73 , 74 ]. However, a report suggests that perinatal exposure to exogenous oxytocin could have neurodevelopmental consequences for the fetus; despite that synthetic oxytocin does not alter in vitro proliferation of neural progenitor cells, it promotes their spontaneous differentiation preferentially into neurons more than astrocytes and oligodendrocytes [ 51 ].…”