An in vitro approach to unravel the modulation of the hypothalamic system by blood-circulating factors

Abstract

The central nervous system (CNS) and the periphery are closely associated in the regulation of body homeostasis. In fact, in both physiological and pathological conditions, the CNS showed to be targeted by peripheral system molecules, which are able to generate adaptive responses under the tight control of the hypothalamus. In spite of having a well-recognized importance, the mechanisms underlying this communication are still unclear. Two major routes have been proposed to explain the transmission of information from the periphery to the CNS: a sensory pathway, through the peripheral nerves and a humoral pathway, through the bloodstream. In the present work, in vitro blood-brain barrier cultures and hypothalamic organotypic cultures were characterized with the main goal to enable the establishment of a platform to investigate the communication between the periphery and the CNS through the humoral pathway.Index Terms-in vitro tools; blood-brain barrier cultures; hypothalamic organotypic cultures; humoral pathway I. CONTEXTThe communication between the central nervous system (CNS) and the periphery is the core of body homeostasis studies. Over the years, a bi-directional flow of information between these two systems responsible for the stabilization of body internal conditions has been well-recognized [1][2]. Indeed, physical and/or chemical stimuli generated within or outside the body and perceived by peripheral organs are able to induce an adaptive response by the central nervous system [3]. Besides the CNS activation in physiological situations, as thermoregulation, reproduction, and food intake, the transfer of information from the periphery to the CNS has demonstrated to be increased under pathological demands, as infections, traumas and tumors [2][4].Since there are different mechanisms involved in the communication between CNS and the periphery concerning body homeostasis, a unified control system is essential. In mammals, the hypothalamus has evolved to serve this purpose [5]. In fact, the hypothalamus showed to be the preferential structure to control body homeostasis due to its ability to integrate peripheral signals and to send efferent hormonal and neuronal signals to regulate peripheral organs [6].A major dilemma has been to clarify how the communication between the CNS and the peripheral organs actually occurs. Two major routes have been proposed to explain this communication: a neural pathway, by the activation of peripheral afferent nerves, and a humoral pathway, through the bloodstream [4] [7].The study of the humoral transmission of peripheral system molecules to the brain has been considerably expanded [8].Unveiling the fundamental features of this communication would be useful for the discovery of new and promising findings in nanomedicine and pharmaceutical fields, potentiating advances in drug delivery research and in the development of new CNS-targeted small and large molecules to treat wide-ranging neurological disorders [8] [9]. However, the CNS is highly protected, and for the blood-circul...