【摘 要】
：
Although neurotoxicity is a prominent feature of beta-amyloid (Aβ), recent data emphasize the existence of synaptic functional roles of the peptide which can modulate the release of several neurotrans
【机 构】
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University of Genoa Italy
【出 处】
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BIT`s 3rd Annual World Congress of NeuroTalk-2012(2012第三届国际神
论文部分内容阅读
Although neurotoxicity is a prominent feature of beta-amyloid (Aβ), recent data emphasize the existence of synaptic functional roles of the peptide which can modulate the release of several neurotransmitters (see Mura et al.PLoS One.2012;7(1):e29661).Accordingly, different Aβ isoforms and oligomers of increasing molecular dimensions may have different biological actions in a continuum from physiology to pathology, determining loss and gains of function along the course of the disease.Using both in vivo (microdialysis) and in vitro (isolated nerve endings) techniques, we indeed showed that low, non neurotoxic, Aβ 1-40 concentrations are able to modulate (predominantly, but not exclusively, to inhibit) the release of several neurotransmitters (dopamine, GABA, aspartate, glutamate) elicited by the stimulation ofpresynaptic cholinergic receptors (including various muscarinic and nicotinic subtypes).The effect is observed in several brain areas such as nucleus accumbens, caudate putamen and hippocampus.In particular, in the latter brain region, beta amyloid may regulate presynaptically the release of both excitatory and inhibitory aminoacids.Even if the exact molecular mechanisms underlying Aβ action are still largely unknown, interactions with nicotinic receptors are suggested from the literature and kinase based transduction systems downstream muscarinic receptors have been observed in our experimental conditions.In pathological conditions this Aβ-mediated synaptic modulation might be related to Aβ-driven functional alterations of neurotransmission in addition and before neurodegeneration.The dysregulation of neurotransmission may in turn produce early cognitive and non-cognitive disturbances based on the neurotransmitter systems and the brain area involved.Hence, the study of the neuromodulatory actions ofAlβ may provide clues to novel therapeutic targets and suggest caution and in depth investigation of the effects of Aβ neutralizing antibodies on neurotransmitter dynamics.
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