The antiepileptogenic effect of low-frequency stimulation on perforant path kindling involves changes in regulators of G-protein signaling in rat.
G-protein coupled receptors may have a role in mediating the antiepileptogenic effect of low-frequency stimulation (LFS) on kindling acquisition. This effect is accompanied by changes at the intracellular level of cAMP. In the present study, the effect of rolipram as a phosphodiesterase inhibitor on the antiepileptogenic effect of LFS was investigated. Meanwhile, the expression of αs- and αi-subunit of G proteins and regulators of G-protein signaling (RGS) proteins following LFS application was measured. Male Wistar rats were kindled by perforant path stimulation in a semi-rapid kindling manner (12 stimulations per day) during a period of 6days. Application of LFS (0.1ms pulse duration at 1Hz, 200 pulses, 50-150μA, 5min after termination of daily kindling stimulations) to the perforant path retarded the kindling development and prevented the kindling-induced potentiation and kindling-induced changes in paired pulse indices in the dentate gyrus. Intra-cerebroventricular microinjection of rolipram (0.25μM) partially prevented these LFS effects. Twenty-four hours after the last kindling stimulation, the dentate gyrus was removed and changes in protein expression were measured by Western blotting. There was no significant difference in the expression of α-subunit of Gsand Gi/oproteins in different experimental groups. However, application of LFS during the kindling procedure decreased the expression RGS4 and RGS10 proteins (that reduce the activity of Gi/o) and prevented the kindling-induced decrease of RGS2 protein (which reduces the Gsactivity). Therefore, it can be postulated that the Gi/oprotein signaling pathways may be involved in antiepileptogenetic effect of LFS, and this is why decreasing the cAMP metabolism by rolipram attenuates this effect of LFS.
Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Simin
S
Namvar
Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Yaghoub
Y
Fathollahi
Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Mohammad
M
Javan
Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Maryam
M
Zeraati
Cellular and Molecular Research Center, Department of Physiology and Pharmacology, School of Medicine, Sabzevar University of Medical Sciences, Sabzevar, Iran.
Mohammad
M
Mohammad-Zadeh
Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Amir
A
Shojaei
Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. Electronic address: mirnajaf@modares.ac.ir.
Javad
J
Mirnajafi-Zadeh
D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use; D001703:Biophysics; D004195:Disease Models, Animal; D004558:Electric Stimulation / Q000379:methods*; D004827:Epilepsy / Q000628:therapy*; D019204:GTP-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D007696:Kindling, Neurologic; D008297:Male; D019580:Perforant Pathway / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D020889:Rolipram / Q000627:therapeutic use; D015398:Signal Transduction / Q000502:physiology*; D013997:Time Factors
D000928:Antidepressive Agents; D019204:GTP-Binding Proteins; D020889:Rolipram
Brain stimulation; Dentate gyrus; Regulators of G-protein signaling; Seizure