The expression changes of EphA3 receptor during synaptic plasticity in mouse hippocampus through activation of nicotinic acetylcholine receptor.
We have reported that systemic application of nicotinic agonists results in expression of a long-term potentiation-like facilitation, a model of synaptic plasticity, in the mouse hippocampus in vivo. Eph receptors and their ephrin ligands, are thought to participate in synaptic plasticity. The present study was conducted to clarify the involvement of EphA3 receptor in synaptic plasticity by investigating the time-dependent change of the expression levels of EphA3 receptor during long-term potentiation-like facilitation in the mouse hippocampus. EphA3 receptor mRNA and protein expression was found in adult mouse hippocampus. EphA3 receptor was localized in neuronal cells but not astrocytes or microglia of hippocampus. After intraperitoneal application of nicotine (3 mg/kg), the protein expression of EphA3 receptor in hippocampus increased during 2-24-h period, significantly increasing during 2-12-h period, and finally returned to the basal level in 72 h, although the mRNA expression of EphA3 receptor was not changed for 24 h. This enhanced expression of EphA3 receptor protein at 4 h was inhibited by pretreatment of mecamylamine (0.5 mg/kg, intraperitoneally), a nonselective nicotinic acetylcholine receptor antagonist. Our findings demonstrated that EphA3 receptor localized only in neuronal cells of the hippocampus was enhanced without transcriptional regulation during synaptic plasticity through activation of the nicotinic acetylcholine receptor. These results suggest that the enhancement of EphA3 receptor after synaptic plasticity may contribute to long-lasting synaptic plasticity through positive, feedforward mechanisms.
Department of Pharmaceutical Health Care, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, Himeji, Japan.
Tooru
T
Nakamura-Hirota
Keiichi
K
Kadoyama
Masaoki
M
Takano
Mieko
M
Otani
Shogo
S
Matsuyama
D000818:Animals; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009538:Nicotine / Q000378:metabolism; D036121:Receptor, EphA3 / Q000378:metabolism*; D011978:Receptors, Nicotinic / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
D011978:Receptors, Nicotinic; D009538:Nicotine; C491717:Epha3 protein, mouse; D036121:Receptor, EphA3