Integrins, synaptic plasticity and epileptogenesis.
A number of processes are thought to contribute to the development of epilepsy including enduring increases in excitatory synaptic transmission, changes in GABAergic inhibition, neuronal cell death and the development of aberrant innervation patterns in part arising from reactive axonal growth. Recent findings indicate that adhesion chemistries and, most particularly, activities of integrin class adhesion receptors play roles in each of these processes and thereby are likely to contribute significantly to the cell biology underlying epileptogenesis. As reviewed in this chapter, studies of long-term potentiation have shown that integrins are important for stabilizing activity-induced increases in synaptic strength and excitability. Other work has demonstrated that seizures, and in some instances subseizure neuronal activity, modulate the expression of integrins and their matrix ligands and the activities of proteases which regulate them both. These same adhesion proteins and proteases play critical roles in axonal growth and synaptogenesis including processes induced by seizure in adult brain. Together, these findings indicate that seizures activate integrin signaling and induce a turnover in adhesive contacts and that both processes contribute to lasting changes in circuit and synaptic function underlying epileptogenesis.
Gall
Christine M
CM
Department of Anatomy and Neurobiology, University of California at Irvine, USA.
Lynch
Gary
G
D000818:Animals; D001921:Brain / Q000503:physiopathology*; D004827:Epilepsy / Q000503:physiopathology*; D006801:Humans; D016023:Integrins / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*
D016023:Integrins