Oxytocin sets the stage for childbirth by initiating uterine contractions, lactation and maternal bonding behaviours. Mice lacking secreted oxcytocin ( Oxt −/− , Cd38 −/− ) or its receptor ( Oxtr −/− ) fail to nurture. Normal maternal behaviour is restored by peripheral oxcytocin replacement in Oxt −/− and Cd38 −/− , but not Oxtr −/− mice, implying that circulating oxcytocin crosses the blood-brain barrier. Exogenous oxcytocin also has behavioural effects in humans. However, circulating polypeptides are typically excluded from the brain. We show that oxcytocin is transported into the brain by receptor for advanced glycation end-products (RAGE) on brain capillary endothelial cells. The increases in oxcytocin in the brain which follow exogenous administration are lost in Ager −/− male mice lacking RAGE, and behaviours characteristic to abnormalities in oxcytocin signalling are recapitulated in Ager −/− mice, including deficits in maternal bonding and hyperactivity. Our findings show that RAGE-mediated transport is critical to the behavioural actions of oxcytocin associated with parenting and social bonding.

Neuroinflammation is a complex inflammatory process in the central nervous system, which is sought to play an important defensive role against various pathogens, toxins or factors that induce neurodegeneration. The onset of neurodegenerative diseases and various microbial infections are counted as stimuli that can challenge the host immune system and trigger the development of neuroinflammation. The homeostatic nature of neuroinflammation is essential to maintain the neuroplasticity. Neuroinflammation is regulated by the activity of neuronal, glial, and endothelial cells within the neurovascular unit, which serves as a “platform” for the coordinated action of pro- and anti-inflammatory mechanisms. Production of inflammatory mediators (cytokines, chemokines, reactive oxygen species) by brain resident cells or cells migrating from the peripheral blood, results in the impairment of blood-brain barrier integrity, thereby further affecting the course of local inflammation. In this review, we analyzed the most recent data on the central nervous system inflammation and focused on major mechanisms of neurovascular unit dysfunction caused by neuroinflammation and infections.

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The excitation/inhibition (E/I) balance controls the synaptic inputs to prevent the inappropriate responses of neurons to input strength, and is required to restore the initial pattern of network activity. Various neurotransmitters affect synaptic plasticity within neural networks via the modulation of neuronal E/I balance in the developing and adult brain. Less is known about the role of E/I balance in the control of the development of the neural stem and progenitor cells in the course of neurogenesis and gliogenesis. Recent findings suggest that neural stem and progenitor cells appear to be the target for the action of GABA within the neurogenic or oligovascular niches. The same might be true for the role of neuropeptides (i.e. oxytocin) in neurogenic niches. This review covers current understanding of the role of E/I balance in the regulation of neuroplasticity associated with social behavior in normal brain, and in neurodevelopmental and neurodegenerative diseases. Further studies are required to decipher the GABA-mediated regulation of postnatal neurogenesis and synaptic integration of newly-born neurons as a potential target for the treatment of brain diseases.

Current theories state that Alzheimer's disease (AD) is a vascular disorder that initiates its pathology through cerebral microvascular abnormalities. Endothelial dysfunction caused by the injury or death of endothelial cells contributes to progression of AD. Also, functional relationships between neurons, glial cells, and vascular cells within so-called neurovascular unit are dramatically compromised in AD. Several recent studies have highlighted that endothelial cells might be the target for the toxic action of heavily aggregated proteins, glia-derived cytokines, and stimuli inducing oxidative and metabolic stress in AD brains. Here, we describe the properties of the brain endothelium that contribute to its specific functions in the central nervous system, and how endothelial-neuronal-glial cell interactions are compromised in the pathogenesis of AD. We also discuss the ways in which functioning of endothelial cells can be modulated in cerebral microvessels. Understanding of molecular mechanisms of endothelial injury and repair in AD would give us novel diagnostic biomarkers and pharmacological targets.