The antiepileptogenic effect of electrical stimulation at different low frequencies is accompanied with change in adenosine receptors gene expression in rats

Abstract

SUMMARYPurpose: Previous studies have shown that the anticonvulsant effects of low-frequency stimulation (LFS) can be affected by activation of adenosine receptors. In the present study, the effect of LFS at different frequencies on kindling rate and adenosine receptors gene expression was investigated. Methods: Animals were kindled by perforant path stimulation in a rapid kindling manner. LFS (0.5, 1, and 5 Hz) was applied after termination of each kindling stimulation. Seizure severity was measured according to behavioral and electrophysiologic parameters. At the end of the experiments, adenosine A 1 and A 2A receptor gene expression were measured. Results: The inhibitory effect of LFS on kindling acquisition was observed at all frequencies. In addition, the inhibitory action of LFS on enhancement of field excitatory postsynaptic potential slope and population spike amplitude during kindling acquisition was not affected by the LFS frequency. However, the effects of LFS on pairedpulse recordings were greater at frequency of 5 Hz. Application of LFS during kindling acquisition also prevented the kindling induced decrease in the A 1 receptor gene expression and attenuated the level of A 2A receptor gene expression in the dentate gyrus. These effects were also greater at the frequency of 5 Hz. Discussion: According to these data, it may be suggested that the antiepileptogenic effects of LFS, developed through inhibition of synaptic transmission in the dentate gyrus, is mediated somehow through preventing the decrease of A 1 receptor and through attenuating the A 2A receptor gene expression. These effects might be dependent on the frequency of LFS.

The antiepileptogenic effect of low-frequency stimulation on perforant path kindling involves changes in regulators of G-protein signaling in rat

“…In conclusion, obtained results in combined with our previous experiments (Sadegh et al, 2007;Jahanshahi et al, 2009;Mohammad-Zadeh et al, 2009) show a possible role for G i/o protein activation in mediating the antiepileptogenic effects of LFS. We summarized this information in figure 6.…”

“…Obtained results indicated that LFS administration could slow down the acquisition of perforant path rapid kindling seizures. Similar our previous reports (Mohammad-Zadeh et al, 2007;Jahanshahi et al, 2009;Mohammad-Zadeh et al, 2009), more stimulations were needed in animals that received LFS during kindling procedure to achieve higher seizure stages. In addition, their cumulative ADDs during 7 days of stimulations were lower than kindled animals.…”

“…Our previous studies showed that activation of two G protein-coupled receptors, (adenosine A 1 and galanin GalR1 and GalR2) may have a role in mediating the anticonvulsant action of LFS in perforant path kindling (Sadegh et al, 2007;Jahanshahi et al, 2009;Mohammad-Zadeh et al, 2009). We reported that the antiepileptogenic effects of LFS on perforant path kindling are exerted through activation of adenosine A 1 receptors (Jahanshahi et al, 2009;Mohammad-Zadeh et al, 2009) and are accompanied with prevention of the kindling-induced increase in cAMP levels (Mohammad-Zadeh et al, 2009). There is a strong relationship between cAMP concentration and seizure severity (Myllyla et al, 1975;Kuriyama and Kakita, 1980;Shigeru, 1983).…”

The Antiepileptic Potential of Nucleosides

“…For example, low or moderate Ado concentrations in the human cerebral cortex and hippocampus correlate well with the medium to high A 1 receptor expression in these brain regions [30,56] suggesting the involvement of Ado and its receptors in the modulation of hippocampal and cortical activity in pathological conditions such as epilepsy. It has also been supported by the demonstration of an epilepsy-induced decrease in A 1 receptor expression in chronic seizures [67,[158][159][160]228] and adaptive changes in Ado receptors after seizures [111]. Activation of A 2B receptors by elevated Ado levels may induce the release of proinflammatory interleukin-6 (IL-6) from astrocytes leading to increased expression of A 1 receptors and their functions in the brain [229,230], which may explain (i) the increase of A 1 receptor expression after seizures parallel with increasing Ado level and (ii) the higher level of IL-6 in the brain areas (e.g., in the hippocampus and cortex) of epileptic patients and rats [186,[231][232][233], which may have a protective effect against subsequent seizures [230].…”

Deep Brain Stimulation for the Treatment of Epilepsy: Circuits, Targets, and Trials

“…The anticonvulsant effects of low-frequency stimulation have been correlated with changes in adenosine receptor expression [43], and vagal nerve stimulation has been associated with alterations in a variety of neurotransmitters and hormones in cerebrospinal fluid [44]. Furthermore, the progressive improvement in outcome associated with electrical stimulation for movement disorders [45] and epilepsy (see below) [23,46], suggest that synaptic, neurochemical, and/or expression changes are occurring in response to electrical stimulation of the pathologic neural network.…”