title: Changes in the expression of collapsin response mediator protein-2 during synaptic plasticity in the mouse hippocampus.
abstract: We have previously reported that nicotine application to the adult mouse causing long-term potentiation-like facilitation in vivo in the hippocampus can serve as a model of synaptic plasticity. The present study clarifies the involvement of collapsin response mediator protein-2 (CRMP2) in synaptic plasticity. CRMP2 was detected in hippocampal neurons of adult mice. The levels of CRMP2 mRNA and protein were increased 2-24 hr and 4-24 hr, respectively, after application of nicotine (3 mg/kg, i.p.), finally returning to the basal level by 48 hr. Furthermore, the ratio of phosphorylated CRMP2 (pCRMP2) at Thr514 residue, an inactive form, to total CRMP2 levels was not changed during synaptic plasticity expressed by nicotine, indicating an enhanced level of non-pCRMP2. This increase of CRMP2 was inhibited by blockade of nicotinic acetylcholine receptors (nAChRs) and required activation of both α4β2 and α7 nAChRs. Although the level of ubiquitinated CRMP2 was increased 8 hr after nicotine treatment, the ratio of ubiquitinated CRMP2 to total CRMP2 protein was similar for nicotine-treated and nontreated mice. This study demonstrates that the expression of CRMP2 increases in hippocampal neurons during synaptic plasticity and that the increment is due mainly to mRNA expression. We propose that CRMP2, particularly non-pCRMP2, could contribute to long-lasting synaptic plasticity.
authors.affiliation: Department of Pharmaceutical Health Care, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, Himeji, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Kadoyama
authors.affiliation: Department of Pharmaceutical Health Care, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, Himeji, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsuura
authors.affiliation: Department of Pharmaceutical Health Care, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, Himeji, Japan.
authors.forename: Tooru
authors.initials: T
authors.lastname: Nakamura-Hirota
authors.affiliation: Department of Life Sciences Pharmacy, School of Pharmaceutical Sciences, Kobe Gakuin University, Kobe, Japan.
authors.forename: Masaoki
authors.initials: M
authors.lastname: Takano
authors.affiliation: Department of Life Sciences Pharmacy, School of Pharmaceutical Sciences, Kobe Gakuin University, Kobe, Japan.
authors.forename: Mieko
authors.initials: M
authors.lastname: Otani
authors.affiliation: Department of Pharmaceutical Health Care, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, Himeji, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Matsuyama
mesh_terms: D000818:Animals; D015153:Blotting, Western; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D010766:Phosphorylation; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D018722:Nicotinic Agonists; C095114:collapsin response mediator protein-2; D009538:Nicotine
keywords: CRMP; nicotinic acetylcholine receptor; phosphorylation; synaptic plasticity; ubiquitin