| First Author | Isono T | Year | 2013 |
| Journal | Neurosci Res | Volume | 77 |
| Issue | 3 | Pages | 180-5 |
| PubMed ID | 23994236 | Mgi Jnum | J:204538 |
| Mgi Id | MGI:5532781 | Doi | 10.1016/j.neures.2013.08.005 |
| Citation | Isono T, et al. (2013) Amyloid-beta(2)(5)(-)(3)(5) induces impairment of cognitive function and long-term potentiation through phosphorylation of collapsin response mediator protein 2. Neurosci Res 77(3):180-5 |
| abstractText | Alzheimer's disease (AD) is characterized by amyloid-beta (Abeta) protein and tau deposition in the brain. Numerous studies have reported a central role of Abeta in the development of AD, but the pathogenesis is not well understood. Collapsin response mediator protein 2 (CRMP2), an intracellular protein mediating a repulsive axon guidance molecule, Semaphorin3A, is also accumulated in neurofibrillary tangles in AD brains. To gain insight into the role of CRMP2 phosphorylation in AD pathogenesis, we investigated the effects of Abeta neurotoxicity in CRMP2 phosphorylation-deficient knock-in (crmp2(ki/ki)) mice, in which the serine residue at 522 was replaced with alanine. Intracerebroventricular (i.c.v.) injection of Abeta(2)(5)(-)(3)(5) peptide, a neurotoxic fragment of Abeta protein, to wild-type (wt) mice increased hippocampal phosphorylation of CRMP2. Behavioral assessment revealed that i.c.v. injection of Abeta(2)(5)(-)(3)(5) peptide caused impairment of novel object recognition in wt mice, while the same peptide did not in crmp2(ki/ki) mice. In electrophysiological recording, wt and crmp2(ki/ki) mice have similar input-output basal synaptic transmission and paired-pulse ratios. However, long-term potentiation was impaired in hippocampal slices of Abeta(2)(5)(-)(3)(5) peptide-treated wt but not those of crmp2(ki/ki). Our findings indicate that CRMP2 phosphorylation is required for Abeta-induced impairment of cognitive memory and synaptic plasticity. |
