title: Chronic administration of N-acetyl-D-mannosamine improves age-associated impairment of long-term potentiation in the senescence-accelerated mouse.
abstract: N-Acetyl-D-mannosamine (ManNAc), a precursor of a sialic acid, is recently reported to improve the cognitive function in aged animals. However, the effect of chronic administration of ManNAc on impaired synaptic transmission and plasticity with age still remain unknown. In this study, we electrophysiologically determined the effect of chronic administration of ManNAc on deteriorated synaptic transmission and plasticity using hippocampal slices from senescence-accelerated mouse prone 8 (SAMP8) which shows age-related impairment of learning and memory. Oral administration of ManNAc for 8 weeks improved the field excitatory postsynaptic potentials (fEPSPs) in both SAMP8 and SAM resistant 1 (SAMR1), the control strain of SAMP8, at 14 months of age, but not at 6 months of age. On the other hand, ManNAc administration improved long-term potentiation (LTP), representative of long-term synaptic plasticity, of 6 month-old SAMP8 but not of age-matched SAMR1. In addition, ManNAc improved LTP of 14 month-old SAMR1 but not of age-matched SAMP8. At the same time, we checked the PPR but ManNAc did not affect the PPRs at either before or after high-frequency stimulation for LTP induction. These results indicate that chronic administration of ManNAc improves the age-dependent attenuation of synaptic transmission and LTP, and shows the availability of ManNAc treatment as potential therapeutic application for cognitive dysfunction.
authors.affiliation: Department of Veterinary Pathophysiology and Animal Health, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
authors.forename: Sakiko
authors.initials: S
authors.lastname: Taniguchi
authors.affiliation: Department of Veterinary Pathophysiology and Animal Health, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kuwahara
authors.affiliation: Department of Veterinary Pathophysiology and Animal Health, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan. Electronic address: akoito@mail.ecc.u-tokyo.ac.jp.
authors.forename: Koichi
authors.initials: K
authors.lastname: Ito
mesh_terms: D000375:Aging / Q000235:genetics / Q000502:physiology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D019706:Excitatory Postsynaptic Potentials; D006595:Hexosamines / Q000494:pharmacology*; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D051379:Mice
chemical_list: D006595:Hexosamines; C002022:N-acetylmannosamine
keywords: Aging; Long-term potentiation; N-Acetyl-d-mannosamine; Senescence-accelerated mouse