K. Fuxe

LF. Agnati

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30 Acta Clin Croat. Vol. 52, (Suppl) No. 1, 201353rd International Neuropsychiatric Pula Congress“Integration” is a key term in describing how nervous systemcan perform high level functions. A first condition to have “in-tegration” is the presence of efficient “communicationprocesses” among the parts that have to be combined into theharmonious whole. In this respect, two main types of commu-nication processes, the wiring transmission (WT) and the vol-ume transmission (VT) allow the exchange of signals not onlybetween neurons, but rather among all cell types present in thecentral nervous system (CNS). The major criterion for this clas-sification is the different characteristics of the communicationchannel with physical boundaries well delimited in the case ofWT (axons and their synapses; gap junctions) but not in thecase of VT (the extracellular fluid filled tortuous channels ofthe extracellular space and the cerebrospinal fluid (CSF) filledventricular space and sub-arachnoidal space). Recently, evidenceof subtypes of WT and VT has been obtained, namely the “tun-nelling nanotube type of WT” and the “Roamer type of VT.”In this novel type of VT microvesicles (MVs) are vesicular car-riers for intercellular communication of proteins, mtDNA andRNA flowing in the extracellular fluid of the brain along energygradients to reach target cells. In the tunnelling nanotubes pro-teins, mtDNA and RNA can migrate as well as mitochondria.Although the existence and the role of these new types of in-tercellular communication are still a matter of investigationtheir potential importance for brain function in health and dis-ease is highly likely. The second fundamental condition to have “integration” is therecognition/decoding process of signals at target cell level. As faras this point is concerned, increasing evidence emphasizes theimportance of supra-molecular allosteric complexes of recep-tors generated by direct receptor–receptor interactions or viaadapter proteins. These complexes allow a first integration ofthe incoming chemical signals already at plasma membranelevel.The two basic features of “integration” can be simultaneouslyaffected since intercellular transfer of receptors via the RoamerType of VT is possible (Guescini Exp Brain Res 318: 603-613;2012). The physiological and pathological implications of thesefindings are still unexplored. Actually, the Roamer type of VTcould also be relevant for a new approach to the Brain-BodyMedicine. As a matter of fact, not only has it been shown thatMVs can pass the blood-brain barrier (Colombo Frontiers inPhysiology 29 March 2012) but it has also been pointed out thatan anatomical connection from subarachnoid spaces alongnerves into peripheral tissues represents an important routethrough which pathogenic CSF contents, including possiblyMVs, leave the subarachnoid spaces along nerves to reach theinterstitial fluids of the respective peripheral tissues (Bechter K.NPBR 2011:51-66).NEW VISTAS ON COMMUNICATION MODES AND INTEGRATIVE MECHANISMS OF CHEMICAL SIGNALSAND THEIR POTENTIAL CLINICAL IMPACTAgnati LF., K. FuxeIrccs Lido Venezia; Department of Neuroscience Karolinska Institute StockholmACADEMIC LECTURE

New Vistas on Communication Modes and Integrative Mechanisms of Chemical Signals and their Potential Clinical Impact

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