1,721,140 research outputs found
Astrocyte control of the entorhinal cortex-dentate gyrus circuit: Relevance to cognitive processing and impairment in pathology
Full text linkThe entorhinal cortex-dentate gyrus circuit is centrally involved in memory processing conveying to the hippocampus spatial and nonspatial context information via, respectively, medial and lateral perforant path (MPP and LPP) excitatory projections onto dentate granule cells (GCs). Here, we review work of several years from our group showing that astrocytes sense local synaptic transmission and exert in turn a presynaptic control at PP-GC synapses. Modulation of neurotransmitter release probability by astrocytes sets basal synaptic strength and dynamic range for long-term potentiation of PP-GC synapses. Intriguingly, this astrocyte control is circuit-specific, being present only at MPP-GC (not LPP-GC) synapses, which selectively express atypical presynaptic N-methyl-D-aspartate receptors (NMDAR) suitable to activation by astrocyte-released glutamate. Moreover, the astrocytic control is peculiarly dependent on the cytokine TNFα, which at constitutive levels acts as a gating factor for the astrocyte signaling. During inflammation/infection processes, increased levels of TNFα lead to uncontrolled astrocyte glutamate release, altered PP-GC circuit processing and, ultimately, impaired contextual memory performance. The TNFα-dependent pathological switch of the synaptic control from astrocytes and its deleterious consequences are observed in animal models of HIV brain infection and multiple sclerosis, conditions both known to cause cognitive disturbances in up to 50% of patients. The review also discusses open issues related to the identified astrocytic pathway: its role in contextual memory processing, potential damaging role in Alzheimer's disease, the existence of vesicular glutamate release from DG astrocytes, and the possible synaptic-like connectivity between astrocytic output sites and PP receptive sites
The active role of astrocytes in synaptic transmission
No full textIn the central nervous system, astrocytes form an intimately connected network with neurons, and their processes closely enwrap synapses. The critical role of these cells in metabolic and trophic support to neurons, ion buffering and clearance of neurotransmitters is well established. However, recent accumulating evidence suggests that astrocytes are active partners of neurons in additional and more complex functions. In particular, astrocytes express a repertoire of neurotransmitter receptors mirroring that of neighbouring synapses. Such receptors are stimulated during synaptic activity and start calcium signalling into the astrocyte network. Intracellular oscillations and intercellular calcium waves represent the astrocyte's own form of excitability, as they trigger release of transmitter (i.e. glutamate) via a novel process sensitive to blockers of exocytosis and involving cyclooxygenase eicosanoids. Astrocyte-released glutamate activates receptors on the surrounding neurons and modifies their electrical and intracellular calcium ([Ca2+]i) state. These exciting new findings reveal an active participation of astrocytes in synaptic transmission and the involvement of neuronastrocyte circuits in the processing of information in the brain
Behavioural and biochemical effects in C57BL/6J mice after a prolonged treatment with the δ‐opiate antagonist ICI 154129
No full textA long term treatment with the δ‐selective opiate antagonist NN‐bisallyl‐Tyr‐Gly‐Gly‐ψ‐(CH2S)‐Phe‐Leu‐OH (ICI 154129) produces an increase in the number of δ‐opiate binding sites, whereas the same treatment with the non selective opiate antagonist naloxone results in an enhancement of both μ‐ and δ‐binding sites. This biochemical effect in naloxone‐pretreated mice is paralleled by a more pronounced increase in locomotor activity induced by a challenge dose of morphine. In contrast, no difference in the effect of morphine was seen in ICI 154129‐pretreated mice with respect to control. These data suggest that the locomotor response to morphine in C57 mice is not mediated through δ‐opiate receptors. 1984 Royal Pharmaceutical Society of Great Britai
[Ca2+] modulates the ratio between cycloxygenase and lipoxygenase metabolism of arachidonic acid in homogenates of hippocampal astroglial cultures
No full textWhile studying the enzymatic processing of arachidonic acid (AA) to eicosanoids in homogenates of hippocampal astrocytes, we observed that all the HPLC peaks corresponding to AA metabolites displayed significantly different levels depending on the presence or not of free Ca2+ in the incubation medium. A specific pattern was noticed, i.e. lipoxygenase (LOX) derivatives, in particular 12-hydroxyeicosatetraenoic acid (12-HETE), showed higher levels in medium containing 1 mM Ca2+, while cycloxygenase (COX) products including prostaglandins (PG) F2 alpha, E2 and D2 and 12-hydroxyhepatadecatrienoic acid (12-HHT), were higher in Ca(2+)-free medium. COX metabolism exceeded LOX metabolism by threefold in Ca(2+)-free medium, while it was only 60% of it in 1 mM Ca2+. The total amount of AA processed under the two conditions was identical. These data suggest that free [Ca2+] influences the pattern of AA metabolites formed in hippocampal astrocytes, with possible important implications in view of the distinct roles played by COX and LOX eicosanoids in synaptic transmission and neurotoxicity in this area
The tripartite synapse: glia in synaptic transmission
No full textFor decades glial cells were considered relatively passive supporters of nerve function. It was accepted that they had important roles to play in the structural, metabolic and trophic support of neurons; however, it is now also known that glial cells are active in the processes of synaptic transmission and information processing. Electrophysiological and optical imaging studies demonstrate that glia not only receive coded information concerning neighbouring synaptic events, but also integrate the exchange of rapid signals with nerve cells and exert modulatory influences at the local and long-range levels. As the specific mechanisms and functional consequences of the glial-synaptic relationship becomes clearer, so the broader relevance of these findings can be understood. The Tripartite Synapse: Glia in Synaptic Transmission introduces the concept of glial cells as active elements of the synapse and the nervous circuitry, describes the experimental evidence supporting this and suggests a revised view of brain activity based on this integrated network of interactive neurons and glia. This is a timely and international review of an exciting new field, and will be of interest to neuroscientists, neurobiologists and cell biologistsLND
"Abuso di alcol e di sostanze stupefacenti e psicotrope. Il doping." in "Psichiatria forense, criminologia ed etica psichiatrica" a cura di Vittorio Volterra
No full textSerotonergic modulation of cortical rat noradrenergic system in the mechanism of action of antidepressant drugs
No full textBehavioural and biochemical effects in C57 BL/6J mice after a prolonged treatment with the delta-opiate antagonist ICI 154129
No full textA long term treatment with the delta-selective opiate antagonist NN-bisallyl-Tyr-Gly-Gly-psi-(CH2S)-Phe-Leu-OH (ICI 154129) produces an increase in the number of delta-opiate binding sites, whereas the same treatment with the non selective opiate antagonist naloxone results in an enhancement of both mu- and delta-binding sites. This biochemical effect in naloxone-pretreated mice is paralleled by a more pronounced increase in locomotor activity induced by a challenge dose of morphine. In contrast, no difference in the effect of morphine was seen in ICI 154129-pretreated mice with respect to control. These data suggest that the locomotor response to morphine in C57 mice is not mediated through delta-opiate receptors
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