title: Contrasting features of ERK1/2 activity and synapsin I phosphorylation at the ERK1/2-dependent site in the rat brain in status epilepticus induced by kainic acid in vivo.
abstract: Extracellular signal-regulated kinase 1/2 (ERK1/2) plays diverse roles in the central nervous system. Activation of ERK1/2 has been observed in various types of neuronal excitation, including seizure activity in vivo and in vitro. However, studies examining ERK1/2 activity and its substrate phosphorylation in parallel are scarce especially in seizure models. We have been studying the phosphorylation state of the presynaptic protein, synapsin I at ERK1/2-dependent and -independent sites in various types of seizure models and showed that ERK1/2-dependent phosphorylation of synapsin I was indeed under control of ERK1/2 activity in vivo. To further expand our study, here we examined the effects of prolonged seizure activity on ERK1/2 activity and synapsin I phosphorylation by using status epilepticus induced by kainic acid (KA-SE) in rats in vivo. In KA-SE, robust ERK1/2 activation was observed in the hippocampus, a representative limbic structure, with lesser activation in the parietal cortex, a representative non-limbic structure. In contrast, the phosphorylation level of synapsin I at ERK1/2-dependent phospho-site 4/5 was profoundly decreased, the extent of which was much larger in the hippocampus than in the parietal cortex. In addition, phosphorylation at other ERK1/2-independent phospho-sites in synapsin I also showed an even larger decrease. All these changes disappeared after recovery from KA-SE. These results indicate that the phosphorylation state of synapsin I is dynamically regulated by the balance between kinase and phosphatase activities. The contrasting features of robust ERK1/2 activation yet synapsin I dephosphorylation may be indicative of an irreversible pathological outcome of the epileptic state in vivo.
authors: Department of Information Physiology, National Institute for Physiological Sciences, Okazaki 444-8787, Japan; Department of Physiological Sciences, SOKENDAI (The Graduate University for Advanced Studies), Okazaki 444-8787, Japan. Electronic address: yamagata@nips.ac.jp.
authors: Yoko
authors: Y
authors: Yamagata
authors: Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06511, USA; Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY 10065-6399, USA.
authors: Angus C
authors: AC
authors: Nairn
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D007608:Kainic Acid / Q000633:toxicity*; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D008297:Male; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013226:Status Epilepticus / Q000139:chemically induced* / Q000473:pathology; D016704:Synapsins / Q000378:metabolism*
chemical_list: D018690:Excitatory Amino Acid Agonists; D016704:Synapsins; D048052:Mitogen-Activated Protein Kinase 3; D007608:Kainic Acid
keywords: ERK1/2; Kainic acid; Phosphorylation; Seizure; Status epilepticus; Synapsin I