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.
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.
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在星形胶质细胞中表达突变型胶质纤维酸性蛋白的小鼠中，腺苷水平升高导致海马 CA1 神经元 LTP 逆转（去电位）诱导失败。
DOI：
10.1016/j.brainres.2014.07.005
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发表时间：
2014
期刊：
影响因子：
2.9
通讯作者：
Yamazaki Y.
中科院分区：
文献类型：
--
作者：
Fujii S;Tanaka KF;Ikenaka K;Yamazaki Y.
星形胶质细胞通过释放包括ATP在内的化学递质来调节邻近神经元的活动。与野生型小鼠相比，在星形胶质细胞中表达突变型人胶质细胞酸性蛋白的小鼠的脑脊液中的腺苷水平略微升高，这可能是由于观察到突变型星形胶质细胞释放ATP增加所致，ATP可用于产生腺苷。使用这些突变小鼠的海马切片，我们研究了海马中内源性腺苷水平的增加是否调节CA 1神经元中长时程增强（LTP）的逆转，即去增强（DP）。在野生型小鼠的海马切片中，通过由100 Hz的100个脉冲组成的强直刺激诱导稳定的LTP，并且这通过30 min后施加的1 Hz的500个脉冲的低频刺激（LFS）的序列逆转。在LFS期间，通过应用100 nM腺苷或0.5 nM N6-环戊基腺苷（腺苷A1受体激动剂）抑制DP的诱导，表明细胞外腺苷水平的增加通过作用于腺苷A1受体而减弱DP诱导。与此相反，虽然一个稳定的LTP也诱导突变小鼠海马切片，诱导DP被抑制，但DP可以诱导应用，在LFS期间，50 nM的8-环戊基茶碱，腺苷A1受体拮抗剂。这些结果表明，在突变小鼠海马CA 1区神经元的DP衰减的星形胶质细胞的ATP释放增加导致细胞外腺苷水平的小幅增加。
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 N6-cyclopentyladenosine, an adenosine A1receptor agonist, during LFS, indicating that the increase in extracellular adenosine levels attenuated DP induction by acting on adenosine A1receptors. 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 A1receptor 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.