Enhanced actions of adenosine in medial entorhinal cortex layer II stellate neurons in temporal lobe epilepsy are mediated via A(1)-receptor activation.
Enhanced actions of adenosine in medial entorhinal cortex layer II stellate neurons in temporal lobe epilepsy are mediated via A(1)-receptor activation.
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颞叶癫痫中内侧肠系膜II层神经元中腺苷的增强作用是通过A（1） - 受体受体激活介导的。
DOI：
10.1111/j.1528-1167.2011.03337.x
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发表时间：
2012-01
期刊：
影响因子：
5.6
通讯作者：
Patel MK
中科院分区：
文献类型：
--
作者：
Hargus NJ;Jennings C;Perez-Reyes E;Bertram EH;Patel MK
The adenosinergic system is known to exert an inhibitory affect in the brain and as such adenosine has been considered an endogenous anticonvulsant. Entorhinal cortex (EC) layer II neurons, which serve as the primary input to the hippocampus, are spared in temporal lobe epilepsy (TLE) and become hyperexcitable. Since these neurons also express adenosine receptors, the activity of these neurons may be controlled by adenosine, specifically during seizure activity when adenosine levels are thought to rise. In light of this, we determined if the actions of adenosine on medial EC (mEC) layer II stellate neurons are augmented in TLE and by which receptor subtype. Horizontal brain slices were prepared from rats exhibiting spontaneous seizures (TLE) induced by electrical stimulation and compared with age matched control rats. mEC layer II stellate neurons were visually identified and action potentials (AP) evoked by either a series of depolarizing current injection steps or via presynaptic stimulation of mEC deep layers. The effects of adenosine were compared with actions of adenosine A1 and A2A receptor-specific agonists (CPA and CGS 21680) and antagonists (DPCPX and ZM241385) respectively. Immunohistochemical and qPCR techniques were also employed to assess relative adenosine A1 receptor message and expression. mEC layer II stellate neurons were hyper-excitable in TLE, evoking a higher frequency of AP's when depolarized and generating bursts of AP's when synaptically stimulated. Adenosine reduced AP frequency and synaptically evoked AP's in a dose dependent manner (500 nM – 100 μM); however, in TLE, the inhibitory actions of adenosine occurred at concentrations that were without affect in control neurons. In both cases, the inhibitory actions of adenosine were mediated via activation of the A1 and not the A2A receptor subtype. qPCR and immunohistochemical experiments revealed an up-regulation of the adenosine A1 mRNA and an increase in A1 receptor staining in TLE neurons compared to control. Our data indicates the actions of adenosine on mEC layer II stellate neurons is accentuated in TLE due to an up-regulation of adenosine A1 receptors. Since adenosine levels are thought to rise during seizure activity, activation of adenosine A1 receptors could provide a possible endogenous mechanism to suppress seizure activity and spread within the temporal lobe.
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影响因子：
2.5
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通讯作者：
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