322,937 research outputs found
Understanding wiring and volume transmission
No full textThe proposal on the existence of two main modes of intercellular communication in the central nervous system (CNS) was introduced in 1986 and called wiring transmission (WT) and volume transmission (VT). The major criterion for this classification was the different characteristics of the communication channel with physical boundaries well delimited in the case of WT (axons and their synapses; gap junctions) but not in the case of VT (the extracellular fluid filled tortuous channels of the extracellular space and the cerebrospinal fluid filled ventricular space and sub-arachnoidal space). The basic dichotomic classification of intercellular communication in the brain is still considered valid, but recent evidence on the existence of unsuspected specialized structures for intercellular communication, such as microvesicles (exosomes and shedding vesicles) and tunnelling nanotubes, calls for a refinement of the original classification model. The proposed updating is based on criteria which are deduced not only from these new findings but also from concepts offered by informatics to classify the communication networks in the CNS. These criteria allowed the identification also of new sub-classes of WT and VT, namely the “tunnelling nanotube type of WT” and the “Roamer type of VT.” In this novel type of VT microvesicles are safe vesicular carriers for targeted intercellular communication of proteins, mtDNA and RNA in the CNS flowing in the extracellular fluid along energy gradients to reach target cells. In the tunnelling nanotubes proteins, mtDNA and RNA can migrate as well as entire organelles such as mitochondria. Although the existence and the role of these new types of intercellular communication in the CNS are still a matter of investigation and remain to be fully demonstrated, the potential importance of these novel types of WT and VT for brain function in health and disease is discussed
Influence of SAMe on the modifications of brain poliamine levels in an animal model of depression
No full textThe mechanism(s) of the antidepressant activity of S-adenosyl-L-methionine (SAMe) have not yet been elucidated. SAMe is essential for the synthesis of polyamines, which have a key role in protein synthesis, cell proliferation, and neuronal plasticity. On the other hand, accumulating data indicate that depression is associated with a reduction in regional brain volume and that antidepressants increase neurogenesis in defined brain regions and also influence neuronal plasticity. Here we show that in a validated rat model of depression (chronic unpredictable mild stress-induced anhedonia) there is a significant reduction of putrescine, spermidine and spermine in the hippocampus, and of only putrescine in the nucleus accumbens septi. SAMe, at a fully antidepressant dose (300 mg/kg i.m., daily for 7 days), completely restores the levels of putrescine in the nucleus accumbens, and restores in part the levels of both spermidine and spermine in the hippocampus. These results may suggest (i) a role for brain polyamines in depression and in reward processes, and (ii) that the antidepressant effect of SAMe may be due, at least in part, to a normalization of putrescine levels in the nucleus accumbens septi
Molecular characterization of a defensin in the IZD-MB-0503 cell line derived from immunocytes of the insect Mamestra brassicae (Lepidoptera)
No full textThe induction of anti-microbial peptides against Gram positive and negative bacteria in the IZD-MB-0503 cell line from the lepidopteranMamestra brassicae is demonstrated, while no anti-fungal activity is detected. The identification of a defensin-like molecule active againstGram positive bacteria is described for the first time in Lepidoptera. This molecule shows between 43% and 59% homology with group Adefensins from other dipteran and hymenopteran species.The induction of anti-microbial peptides against Gram positive and negative bacteria in the IZD-MB-0503 cell line from the lepidopteran Mamestra brassicae is demonstrated, while no anti-fungal activity is detected. The identification of a defensin-like molecule active against Gram positive bacteria is described for the first time in Lepidoptera. This molecule shows between 43% and 59% homology with group A defensins from other dipteran and hymenopteran species
Antidiuretic and nephrotoxic effects of putrescine in rats.
No full textPutrescine, intraperitoneally injected either into intact or into hypophysectomized rats, caused a reduction in urine volume at doses of 200–300 mg/kg. At doses of 100 mg/kg or more, there was also a significant loss of potassium. The highest dose (300 mg/kg) caused haemoglobinuria, proteinuria, increased natriuresis, increased urinary osmolarity, reduced aldosteronaemia, ectasis of glomerular capillaries and tubular damage. The underlying mechanisms(s) are probably mostly linked to the strong cationic charge of putrescine and to its binding to fixed anions of tubular-cell membrane
Neuronal correlates to consciousness. The "Hall of Mirrors" metaphor describing consciousness as an epiphenomenon of multiple dynamic mosaics of cortical functional modules.
No full textHumans share the common intuition of a self that has access to an inner ‘theater of mind’
(Baars, 2003). The problem is how this internal theater is formed. Moving from Cook's view
(Cook, 2008), we propose that the ‘sentience’ present in single excitable cells is integrated
into units of neurons and glial cells transiently assembled into “functional modules”
(FMs) organized as systems of encased networks (from cell networks to molecular
networks). In line with Hebb's proposal of ‘cell assemblies’, FMs can be linked to form
higher-order mosaics by means of reverberating circuits. Brain-level subjective awareness
results from the binding phenomenon that coordinates several FM mosaics. Thus,
consciousness may be thought as the global result of integrative processes taking place at
different levels of miniaturization in plastic mosaics. On the basis of these neurobiological
data and speculations and of the evidence of ‘mirror neurons’ the ‘Hall of Mirrors’ is
proposed as a significant metaphor of consciousness
Treatment with polyamine synthesis inhibitors reduces the positive inotropic effect of ouabain, noradrenaline and calcium
No full textPolyamines (putrescine, spermidine and spermine) are considered to act as intracellular second messengers by increasing Ca++ influx and mobilizing intracellular calcium. On the other hand, intracellular Ca++ increase is the common final step of the mechanism of action of many inotropic agents. To discover whether the functional integrity of the cardiac ornithine decarboxylase (ODC)/polyamine system is necessary to cope with a stimulated inotropism, we studied the effect of ouabain, noradrenaline, and calcium on ventricle strips obtained from rats treated with polyamine synthesis inhibitors. The combined administration of methylglioxal bis (guanylhydrazone) (MGBG) (single i.p. injection of 50 mgkg-1) and of alpha-di fluoromethylornithine (DFMO) (100 mgkg-1 every 12 h for 7 consecutive days) caused a 62.5% inhibition of ventricular ODC activity, and a significant decrease of the ventricular content of putrescine and spermidine (-59.5%, and -40.1%, respectively). While the basal isometric tension developed by ventricle strips obtained from rats treated with MGBG+DFMO was similar to that developed by ventricle strips from controls, the response to ouabain (1 microM), noradrenaline (10 microM), or Ca++ (3.6 mM) was significantly reduced. It cannot be excluded that effects of MGBG unrelated to the inhibition of polyamine synthesis may have also concurred in part to influence the effect of ouabain, Ca++ and noradrenaline adversely. However, the present results seem to indicate that the heart response to inotropic agents requires an efficient ODC/polyamine system, polyamines probably being involved in calcium ion movements or affecting the Ca++ sensitivity of contractile proteins
La comunicazione nel Sistema Nervoso Centrale
No full textAddendum all'edizione italiana sui concetti di Volume Transmission e Wiring Transmission nel Sistema Nervoso Central
Theoretical Considerations on the Topological Organization of Receptor Mosaics
No full textThe concept of Receptor Mosaic (RM) is discussed; hence the integrative functions of the assemblage of G-protein coupled receptors physically interacting in the plane of the plasma membrane. The main focus is on a hetero-trimer of G-protein coupled receptors, namely the A2A-D2-CB1 receptor trimer. A bioinformatics analysis was carried out on the amino acid sequence of these receptors to indicate domains possibly involved in the receptor-receptor interactions. Such a bioinformatic analysis was also carried out on the RM formed by mGLU R5, D2 and A2A. The importance of topology, i.e., of the reciprocal localisation of the three interacting receptors in the plan of the membrane for the RM integrative functions is underlined. However, it is also pointed out that this fundamental aspect still waits techniques capable of an appropriate investigation. Finally, it is discussed how RM topology can give hints for a structural definition of the concept of hub receptor. Thus, just as in any network, the receptor operating as a hub is the one that in the molecular network formed by the receptors has the highest number of inputs
Putrescine reverses aconitine-induced arrhythmia in rats
No full textPutrescine, (150-300 mg kg-1 i.v.) injected into anaesthetized rats reversed aconitine-induced arrhythmia and restored sinus rhythm. In the same experimental model, quinidine and lignocaine had a transient therapeutic effect, procainamide was practically ineffective and verapamil worsened the aconitine arrhythmia, causing the death of all treated animals. These data demonstrate that putrescine has an antiarrhythmic effect in an experimental model particularly resistant to usual antiarrhythmic treatments
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