Regional Variations of Spontaneous, Transient Adenosine Release in Brain Slices.
Regional Variations of Spontaneous, Transient Adenosine Release in Brain Slices.
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DOI：
10.1021/acschemneuro.7b00280
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发表时间：
2018-03-21
影响因子：
5
通讯作者：
Venton BJ
中科院分区：
文献类型：
--
作者：
Lee ST;Venton BJ
最近在体内发现了瞬时腺苷信号传导，其中浓度平均为180 nM，持续时间仅为3-4秒。为了快速筛选不同脑区腺苷的形成和调控机制，我们建立了大鼠脑切片模型，研究腺苷瞬变。在前额叶皮层（PFC）、海马（CA 1）和丘脑中比较短暂腺苷事件的频率、浓度和持续时间。PFC中的腺苷瞬变与体内相似，浓度为160 ± 10 nM，并且频繁发生，平均每50 ± 5 s发生一次。在丘脑中，瞬变不常见，每280 ± 40 s发生一次，浓度较低（110 ± 10 nM），但持续时间是PFC的两倍。在海马中，腺苷瞬变的频率低于PFC，每79 ± 7 s发生一次，但平均浓度（240 ± 20 nM）显著较高。腺苷瞬变在应用200 nM河豚毒素后大部分得以维持，这意味着它们不是活性依赖性的。对腺苷A1拮抗剂8-环戊基-1，3-二丙基黄嘌呤（DPCPX）的反应因区域而异; DPCPX对PFC无显著影响，但增加丘脑中的平均瞬时浓度以及海马中的瞬时频率和浓度。因此，可用于激活受体的腺苷的量以及用DPCPX上调腺苷信号传导的能力因脑区域而异。这是设计调节腺苷以引起神经保护作用的治疗的重要考虑。
Transient adenosine signaling has been recently discovered in vivo, where the concentration is on average 180 nM and the duration only 3-4 seconds. In order to rapidly screen different brain regions and mechanisms of formation and regulation, here we develop a rat brain slice model to study adenosine transients. The frequency, concentration, and duration of transient adenosine events were compared in the prefrontal cortex (PFC), hippocampus (CA1), and thalamus. Adenosine transients in the PFC were similar to those in vivo, with a concentration of 160 ± 10 nM, and occurred frequently, averaging one every 50 ± 5 s. In the thalamus, transients were infrequent, occurring every 280 ± 40 s, and lower concentration (110 ± 10 nM), but lasted twice as long as in the PFC. In the hippocampus, adenosine transients were less frequent than in the PFC, occurring every 79 ± 7 s, but the average concentration (240 ± 20 nM) was significantly higher. Adenosine transients are largely maintained after applying 200 nM tetrodotoxin, implying they are not activity dependent. The response to adenosine A1 antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) differed by region; DPCPX had no significant effects in the PFC, but increased the average transient concentration in the thalamus and both the transient frequency and concentration in the hippocampus. Thus, the amount of adenosine available to activate receptors, and the ability to upregulate adenosine signaling with DPCPX, varies by brain region. This is an important consideration for designing treatments that modulate adenosine in order to cause neuroprotective effects.
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影响因子：
5.3
作者：
Miranda MF;Hamani C;de Almeida AC;Amorim BO;Macedo CE;Fernandes MJ;Nobrega JN;Aarão MC;Madureira AP;Rodrigues AM;Andersen ML;Tufik S;Mello LE;Covolan L
通讯作者：
Covolan L
影响因子：
4.7
作者：
Duarte, Joao M. N.;Cunha, Rodrigo A.;Carvalho, Rui A.
通讯作者：
Carvalho, Rui A.
影响因子：
5.3
作者：
Klyuch, Boris P.;Dale, Nicholas;Wall, Mark J.
通讯作者：
Wall, Mark J.
影响因子：
5
作者：
Chauhan, Nikky K.;Young, Andrew M. J.;Gibson, Claire L.;Davidson, Colin
通讯作者：
Davidson, Colin
影响因子：
64.8
作者：
Bunsey, M;Eichenbaum, H
通讯作者：
Eichenbaum, H