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: Yoko Yamagata, Angus C Nairn
• Journal: Brain research (Brain Res) Vol. 1625 Pg. 314-23 (Nov 02 2015) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 26320550 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Excitatory Amino Acid Agonists
• Synapsins
• Mitogen-Activated Protein Kinase 3
• Kainic Acid

Topics

• Animals
• Brain (drug effects, metabolism)
• Disease Models, Animal
• Enzyme Activation (drug effects)
• Excitatory Amino Acid Agonists (toxicity)
• Kainic Acid (toxicity)
• MAP Kinase Signaling System (drug effects, physiology)
• Male
• Mitogen-Activated Protein Kinase 3 (metabolism)
• Phosphorylation (drug effects)
• Rats
• Rats, Wistar
• Status Epilepticus (chemically induced, pathology)
• Synapsins (metabolism)