In vitro effects of cocaine on tunneling nanotube formation and extracellular vesicle release in glioblastoma cell cultures

The effects of cocaine (150 nM, 300 nM, and 150 μM) on human glioblastoma cell cultures were studied on tunneling nanotube formation (1-h cocaine treatment) and extracellular vesicle release (1-, 3-, and 8-h cocaine treatment). Cocaine significantly increased the number of tunneling nanotubes only at the lowest concentration used. The release of extracellular vesicles (mainly exosomes) into the medium was stimulated by cocaine at each concentration used with a maximum effect at the highest concentration tested (150 μM). Moreover, cocaine (150 nM) significantly increased the number of vesicles with 61-80 nm diameter while at concentrations of 300 nM and 150 μM, and the smaller vesicles (30-40 nm diameter) were significantly increased with a reduction of the larger vesicles (41-60 nm diameter). A time dependence in the release of extracellular vesicles was observed. In view of the proposed role of these novel intercellular communication modes in the glial-neuronal plasticity, it seems possible that they can participate in the processes leading to cocaine addiction. The molecular target/s involved in these cocaine effects could be specific molecular components of plasma membrane lipid rafts and/or cocaine-induced modifications in cytoplasmic lipid composition

Adenosine Receptor Heteromers and their Integrative Role in Striatal Function

By analyzing the functional role of adenosine receptor heteromers, we review a series of new concepts that should modify our classical views of neurotransmission in the central nervous system (CNS). Neurotransmitter receptors cannot be considered as single functional units anymore. Heteromerization of neurotransmitter receptors confers functional entities that possess different biochemical characteristics with respect to the individual components of the heteromer. Some of these characteristics can be used as a “biochemical fingerprint†to identify neurotransmitter receptor heteromers in the CNS. This is exemplified by changes in binding characteristics that are dependent on coactivation of the receptor units of different adenosine receptor heteromers. Neurotransmitter receptor heteromers can act as “processors†of computations that modulate cell signaling, sometimes critically involved in the control of pre- and postsynaptic neurotransmission. For instance, the adenosine A1-A2A receptor heteromer acts as a concentration-dependent switch that controls striatal glutamatergic neurotransmission. Neurotransmitter receptor heteromers play a particularly important integrative role in the “local module†(the minimal portion of one or more neurons and/or one or more glial cells that operates as an independent integrative unit), where they act as processors mediating computations that convey information from diverse volume-transmitted signals. For instance, the adenosine A2A-dopamine D2 receptor heteromers work as integrators of two different neurotransmitters in the striatal spine module

Special issue: Proceedings of the Wenner-Gren Foundation symposium - Receptor-receptor interactions among heptaspanning membrane receptors: From structure to function - Concluding remarks

NON DISPONIBIL

Wiring and volume transmission in the central nervous system: The concept of closed and open synapses

During the past two decades, several revisions of the concepts underlying interneuronal communication in the central nervous system (CNS) have been advanced. Our group has proposed to classify intercellular communication in the CNS under two general frames: 'wiring' (WT) and 'volume' transmission (VT). WT is characterized by a single 'transmission channel' made by cellular (neuronal or glial) structures and with a region of discontinuity not larger than a synaptic cleft. VT is characterized by the diffusion from a cell source (neuronal or glial) of chemical and electrical signals in the extracellular fluid (ECF) for a distance larger than the synaptic cleft Based on morphological and functional characteristics, and in light of the distinction proposed, six main modes of intercellular communication can be recognized in the CNS: gap-junction, membrane juxtaposition, and closed synapse (which represent WT-type modes of communication); open synapse, paracrine transmission and endocrine-like transmission (which represent VT-type modes of communication). Closed and open synapses are distinguished on the basis of the sealing of the signal within or the leakage of the signal outside the synapse Intra-synaptic restriction or extra-synaptic diffusion of transmitters are insured by a number of anatomical arrangements (e.g. glial ensheathment of synapse, size of the synaptic cleft) and functional mechanisms (e.g. density and location of transmitter re-uptake sites and metabolic enzymes). Some central synapses can switch from closed to open state and vice versa, e.g. by changing the amount of transmitter released. Finally, a synapse containing several transmitters can work as an open synapse for one transmitter and as a closed synapse for another

Special issue: Proceedings of the Wenner-Gren Foundation symposium - Receptor-receptor interactions among heptaspanning membrane receptors: From structure to function - Introductory remarks

NON DISPONIBIL

Does the human brain have unique genetically determined networks coding logical and ethical principles and aesthetics? From Plato to novel mirror networksstar.

Starting from the assumption that philosophers carry out “experiments” not on concrete objects, but on concepts and relationships between concepts, it could be postulated that the philosopher's way to proceed is not basically different from that followed by scientists. From this similarity of approaches it can be considered that some philosophical problems and theories have a high impact on how to address scientific investigations. One of these issues is certainly the philosophical debate over innate ideas, which is central to the conflict between rationalist and empiricist epistemologies. We started our reflections on the possible presence of innate ideas in the human brain from the observation that there exists strong experimental support for the view that not only complex behaviours (e.g., sexual courtship, parental care) but also aesthetic and ethic judgements can be, at least in part, genetically determined. On these grounds it is suggested that neurobiological findings can give important contributions to the philosophical debate on innatism by putting forward possible explanatory models and heuristic hypotheses

A simple mathematical model of cooperativity in receptor mosaics based on the symmetry rule

The phenomenon of receptor-receptor interactions was hypothesized about 20 years ago. It has been demonstrated by now that receptor-receptor interactions between G-protein coupled receptors (GPCRs) occur at plasma membrane level and result in the reciprocal modulation of their binding characteristics (i.e., cooperativity). One of the most important feature of this phenomenon is the concept of cluster of receptors, or receptor mosaic (RM). However, no proper mathematical approach has still been available to characterize RMs as far as their receptor composition, receptor topography and order of receptor activation inside the RM. This paper tries to fill the gap. A simple mathematical approach to the cooperativity in RMs formed by dimers of identical receptors and/or by iso-receptors is proposed. To this aim the so-called symmetry rule has been considered. This approach allows to describe by means of a simple energy function the effects of receptor composition (number of dimers), spatial organisation (respective location of the dimers) and order of activation (order according to which the single receptors are ligated) on the integrative cooperativity (index) of the RMs