title: Increased adenosine levels in mice expressing mutant glial fibrillary acidic protein in astrocytes result in failure of induction of LTP reversal (depotentiation) in hippocampal CA1 neurons.
abstract: Astrocytes regulate the activity of neighboring neurons by releasing chemical transmitters, including ATP. Adenosine levels in the cerebrospinal fluid of mice that express a mutant human glial fibrillary acidic protein in astrocytes are slightly elevated compared to those in wild type mice and this might result from the observed increased release by mutant astrocytes of ATP, which can be used to produce adenosine. Using hippocampal slices from these mutant mice, we examined whether the increased endogenous adenosine levels in the hippocampus modulate the reversal of long-term potentiation (LTP), i.e. depotentiation (DP), in CA1 neurons. In hippocampal slices from wild type mice, a stable LTP was induced by tetanic stimulation consisting of 100 pulses at 100 Hz, and this was reversed by a train of low frequency stimulation (LFS) of 500 pulses at 1 Hz applied 30 min later. This induction of DP was inhibited by application of either 100 nM adenosine or 0.5 nM N(6)-cyclopentyladenosine, an adenosine A1 receptor agonist, during LFS, indicating that the increase in extracellular adenosine levels attenuated DP induction by acting on adenosine A1 receptors. In contrast, although a stable LTP was also induced in hippocampal slices from mutant mice, induction of DP was inhibited, but DP could be induced by application, during LFS, of 50 nM 8-cyclopentyltheophylline, an adenosine A1 receptor antagonist. These results suggest that a small increase in extracellular adenosine levels resulting from increased ATP release by astrocytes results in attenuation of DP in hippocampal CA1 neurons in the mutant mice.
authors.affiliation: Department of Physiology, Yamagata University School of Medicine, Yamagata 990-9585, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fujii
authors.affiliation: Department of Neuropsychiatry, School of Medicine, Keio University, Tokyo 160-8582, Japan.
authors.forename: Kenji F
authors.initials: KF
authors.lastname: Tanaka
authors.affiliation: Division of Neurobiology and Bioinformatics, National Institute for Physiological Sciences, Okazaki 444-8787, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ikenaka
authors.affiliation: Department of Physiology, Yamagata University School of Medicine, Yamagata 990-9585, Japan. Electronic address: yyamazak@med.id.yamagata-u.ac.jp.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Yamazaki
mesh_terms: D000241:Adenosine / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism*; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D058906:Purinergic P1 Receptor Agonists / Q000494:pharmacology; D043682:Receptor, Adenosine A1 / Q000378:metabolism
chemical_list: D005904:Glial Fibrillary Acidic Protein; D058906:Purinergic P1 Receptor Agonists; D043682:Receptor, Adenosine A1; D000241:Adenosine
keywords: ATP; Adenosine; Astrocyte; Depotentiation; Hippocampus; LTP