Increased receptor density of α2 adrenoceptors and GABAA α5 receptors in limbic brain regions in the domoic acid rat model of epilepsy

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Increased receptor density of α2 adrenoceptors and GABAA α5 receptors in limbic brain regions in the domoic acid rat model of epilepsy. / Thomsen, Majken; Lillethorup, Thea Pinholt; Wegener, Gregers; Tasker, Andrew; Landau, Anne M.

2015. Abstract from OAK Meeting 2015, Aarhus, Denmark.

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@conference{6a9e3d163bbc4590a2059f34f0aa0d88,
title = "Increased receptor density of α2 adrenoceptors and GABAA α5 receptors in limbic brain regions in the domoic acid rat model of epilepsy",
abstract = "Background: The presymptomatic events involved in epilepsy remain elusive but represent a chance to understand disease development and stop the pathogenic processes leading to chronic epilepsy. Previous studies have found increased levels of α2 adrenoceptors and decreased levels of glutamic acid decarboxylase, a catalyst of the decarboxylation of glutamate to GABA.Methods: Male Sprague-Dawley rats (N=3) were injected (s.c.) daily from postnatal day 8-14 with saline or sub-convulsive doses of the glutamate agonist DOM (20µg/kg). At ~120 days of age the rats were decapitated. The brains were removed, fresh frozen and cut into 20 µM thick slices. Autoradiography was performed using tracers of the α5 subtype of the GABAA receptor ([11C]Ro15-4513) and the α2 adrenoceptors ([3H]RX821002) to determine the binding in limbic brain regions.Results: The binding of postsynaptic GABA receptors was significantly increased in the dorsal hippocampus and basolateral amygdala of the DOM rats. A trend towards an increase in the density of α2 adrenoceptors was found throughout the limbic system of the DOM rats compared to controls.Conclusion: Although preliminary, the increase in postsynaptic GABA receptor concentrations in DOM rats may represent a compensatory up-regulation in response to reduced GABAergic input. Noradrenaline reduces neuronal excitability. Elevated receptor expression could be a protective mechanism that attempts to compensate for the lowered seizure threshold caused by DOM.",
author = "Majken Thomsen and Lillethorup, {Thea Pinholt} and Gregers Wegener and Andrew Tasker and Landau, {Anne M.}",
year = "2015",
month = "5",
language = "English",
note = "null ; Conference date: 29-05-2015 Through 29-05-2015",

}

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TY - ABST

T1 - Increased receptor density of α2 adrenoceptors and GABAA α5 receptors in limbic brain regions in the domoic acid rat model of epilepsy

AU - Thomsen, Majken

AU - Lillethorup, Thea Pinholt

AU - Wegener, Gregers

AU - Tasker, Andrew

AU - Landau, Anne M.

PY - 2015/5

Y1 - 2015/5

N2 - Background: The presymptomatic events involved in epilepsy remain elusive but represent a chance to understand disease development and stop the pathogenic processes leading to chronic epilepsy. Previous studies have found increased levels of α2 adrenoceptors and decreased levels of glutamic acid decarboxylase, a catalyst of the decarboxylation of glutamate to GABA.Methods: Male Sprague-Dawley rats (N=3) were injected (s.c.) daily from postnatal day 8-14 with saline or sub-convulsive doses of the glutamate agonist DOM (20µg/kg). At ~120 days of age the rats were decapitated. The brains were removed, fresh frozen and cut into 20 µM thick slices. Autoradiography was performed using tracers of the α5 subtype of the GABAA receptor ([11C]Ro15-4513) and the α2 adrenoceptors ([3H]RX821002) to determine the binding in limbic brain regions.Results: The binding of postsynaptic GABA receptors was significantly increased in the dorsal hippocampus and basolateral amygdala of the DOM rats. A trend towards an increase in the density of α2 adrenoceptors was found throughout the limbic system of the DOM rats compared to controls.Conclusion: Although preliminary, the increase in postsynaptic GABA receptor concentrations in DOM rats may represent a compensatory up-regulation in response to reduced GABAergic input. Noradrenaline reduces neuronal excitability. Elevated receptor expression could be a protective mechanism that attempts to compensate for the lowered seizure threshold caused by DOM.

AB - Background: The presymptomatic events involved in epilepsy remain elusive but represent a chance to understand disease development and stop the pathogenic processes leading to chronic epilepsy. Previous studies have found increased levels of α2 adrenoceptors and decreased levels of glutamic acid decarboxylase, a catalyst of the decarboxylation of glutamate to GABA.Methods: Male Sprague-Dawley rats (N=3) were injected (s.c.) daily from postnatal day 8-14 with saline or sub-convulsive doses of the glutamate agonist DOM (20µg/kg). At ~120 days of age the rats were decapitated. The brains were removed, fresh frozen and cut into 20 µM thick slices. Autoradiography was performed using tracers of the α5 subtype of the GABAA receptor ([11C]Ro15-4513) and the α2 adrenoceptors ([3H]RX821002) to determine the binding in limbic brain regions.Results: The binding of postsynaptic GABA receptors was significantly increased in the dorsal hippocampus and basolateral amygdala of the DOM rats. A trend towards an increase in the density of α2 adrenoceptors was found throughout the limbic system of the DOM rats compared to controls.Conclusion: Although preliminary, the increase in postsynaptic GABA receptor concentrations in DOM rats may represent a compensatory up-regulation in response to reduced GABAergic input. Noradrenaline reduces neuronal excitability. Elevated receptor expression could be a protective mechanism that attempts to compensate for the lowered seizure threshold caused by DOM.

M3 - Conference abstract for conference

ER -