Potential Role of Drebrin A, an F-Actin Binding Protein, in Reactive Synaptic Plasticity after Pilocarpine-Induced Seizures: Functional Implications in Epilepsy
Several neurological disorders characterized by cognitive deficits, including Alzheimer's disease, down syndrome, and epilepsy exhibit abnormal spine density and/or morphology. Actin-based cytoskeleton network dynamics is critical for the regulation of spine morphology and synaptic function. In this paper, I consider the functions of drebrin A in cell shaping, spine plasticity, and synaptic function. Developmentally regulated brain protein (drebrin A) is one of the most abundant neuron-specific binding proteins of F-actin and its expression is increased in parallel with synapse formation. Drebrin A is particularly concentrated in dendritic spines receiving excitatory inputs. Our recent findings point to a critical role of DA in dendritic spine structural integrity and stabilization, likely via regulation of actin cytoskeleton dynamics, and glutamatergic synaptic function that underlies the development of spontaneous recurrent seizures in pilocarpine-treated animals. Further research into this area may provide useful insights into the pathology of status epilepticus and epileptogenic mechanisms and ultimately may provide the basis for future treatment options. 1. Introduction The human brain is composed by hundred billion neurons interconnected in order to form functional neuronal networks that control higher brain functions, such as learning, thoughts, emotions, and memory throughout life. The communication between neurons within neuronal networks is mediated via synapses. Tight control mechanisms of the formation, growth, and connectivity of synapses are crucial for accurate neural network activity and normal brain function. For example, the development, remodeling, and elimination of excitatory synapses on dendritic spines represent ways of refining the microcircuitry in the brain. Thus, when processes involved in structural synapses and/or synaptic function go awry, either during normal aging or in disease, dysfunction of the organism occurs. 2. Dendritic Spines and Functions Dendritic spines are tiny protrusions from the dendritic tree that serve as the postsynaptic component for the vast majority of excitatory synapses in the central nervous system [1–4]. These protrusions are found on most excitatory and some inhibitory neurons [2, 3, 5, 6]. The dendritic spine consists of a bulbous head connected to the dendritic shaft by a narrow neck [1, 7]. The narrow neck of the spine forms a spatially isolated compartment where molecular signals can rise and drop without diffusing to neighboring spines along the parent dendrite, thus allowing the isolation
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