Journal
BRAIN RESEARCH
Volume 1578, Issue -, Pages 1-13Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.brainres.2014.07.005
Keywords
Adenosine; ATP; Astrocyte; LTP; Depotentiation; Hippocampus
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Funding
- JSPS KAKENHI [24500434, 25117005, 25350986]
- MEXT ICAKENHI [23680042]
- Grants-in-Aid for Scientific Research [24500434, 25350986, 25117005] Funding Source: KAKEN
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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 A(1) receptor agonist, during LFS, indicating that the increase in extracellular adenosine levels attenuated DP induction by acting on adenosine A(1) 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 A(1) 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. (C) 2014 Elsevier B.V. All rights reserved.
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