Microtubule Dynamics and Neuronal Excitability: Advances on Cytoskeletal Components Implicated in Epileptic Phenomena
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REVIEW PAPER
Microtubule Dynamics and Neuronal Excitability: Advances on Cytoskeletal Components Implicated in Epileptic Phenomena Giuditta Gambino1 · Valerio Rizzo1 · Giuseppe Giglia1 · Giuseppe Ferraro1 · Pierangelo Sardo1 Received: 19 May 2020 / Accepted: 5 September 2020 © The Author(s) 2020
Abstract Extensive researches have deepened knowledge on the role of synaptic components in epileptogenesis, but limited attention has been devoted to the potential implication of the cytoskeleton. The study of the development of epilepsy and hyperexcitability states involves molecular, synaptic, and structural alterations of neuronal bioelectric activity. In this paper we aim to explore the neurobiological targets involved in microtubule functioning and cytoskeletal transport, i.e. how dynamic scaffolding of microtubules can influence neuronal morphology and excitability, in order to suggest a potential role for microtubule dynamics in the processes turning a normal neuronal network in a hyperexcited one. Pathophysiological alterations of microtubule dynamics inducing neurodegeneration, network remodeling and relative impairment on synaptic transmission were overviewed. Recent researches were reported on the phosphorylation state of microtubule-associated proteins such as tau in neurodegenerative diseases and epileptic states, but also on the effect of microtubule-active agents influencing cytoskeleton destabilization in epilepsy models. The manipulation of microtubule polymerization was found effective in the modulation of hyperexcitability. In addition, it was considered the importance of microtubules and related neurotrophic factors during neural development since they are essential for the formation of a properly functional neuronal network. Otherwise, this can lead to cognitive deficits, hyperexcitability phenomena and neurodevelopmental disorders. Lastly, we evaluated the role of microtubule dynamics on neuronal efficiency considering their importance in the transport of mitochondria, cellular elements fulfilling energy requirements for neuronal activity, and a putative influence on cannabinoid-mediated neuroprotection. This review provides novel perspectives for the implication of microtubule dynamics in the development of epileptic phenomena. Keywords Hyperexcitability · Microtubules · Epilepsy · Neurodevelopment · Cannabinoids · Neuroprotection
Introduction: Epilepsy and Possible Neurobiological Targets Epilepsy is a common, chronic neurological disorder, characterized by recurring, unprovoked seizures that often requires long-term therapy with antiepileptic drugs (AEDs), unless it appears as drug-refractory (Schmidt and Löscher 2005; Tischfield et al. 2010). Epileptogenesis comprises the sequence of events leading to abnormal, hypersynchronous discharge of specific populations of cortical neurons (Bromfield et al. 2006). Epileptic seizures are characterized by * Giuseppe Giglia [email protected] 1
Department of Experimental Biomedicine, Neuroscience and Advanced Diagnostics (Bi.N.D.), Sezione Di
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