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 substrat...

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Published in:Brain research 2015-11, Vol.1625, p.314-323
Main Authors: Yamagata, Yoko, Nairn, Angus C
Format: Article
Language:English
Subjects:
Animals
Brain - drug effects
Brain - metabolism
Disease Models, Animal
Enzyme Activation - drug effects
ERK1/2
Excitatory Amino Acid Agonists - toxicity
Kainic acid
Kainic Acid - toxicity
Male
MAP Kinase Signaling System - drug effects
MAP Kinase Signaling System - physiology
Mitogen-Activated Protein Kinase 3 - metabolism
Neurology
Phosphorylation
Phosphorylation - drug effects
Rats
Rats, Wistar
Seizure
Status epilepticus
Status Epilepticus - chemically induced
Status Epilepticus - pathology
Synapsin I
Synapsins - metabolism
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Summary: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.
ISSN:0006-8993
1872-6240
DOI:10.1016/j.brainres.2015.08.023