GABAA receptor impairment in the genetic absence epilepsy rats from Strasbourg (GAERS): an immunocytochemical and receptor binding autoradiographic study.
Some aspects of the GABA and cholinergic systems have been investigated in the cortex and thalamus of GAERS Wistar rats, a model of petit-mal epilepsy, and in a non-epileptic control strain. GABA and its synthetic enzyme, glutamic acid decarboxylase (GAD), were located by immunocytochemistry; the GABAA receptors were evaluated by autoradiography of GABA-enhanced 3H-flunitrazepam binding and by immunocytochemistry using specific antibodies against the beta 2-beta 3 subunits of GABAA receptor protein. GABA and GAD immunocytochemistry did not show up any difference in density or distribution of immunoreactive elements (fibers, terminals and neurons) between epileptic and control animals, but autoradiographic and immunocytochemical studies showed a decreased enhancement of 3H-flunitrazepam binding and of beta 2-beta 3 subunits of GABAA receptor in the sensorimotor cortex and anterior thalamic areas of the epileptic strain. No differences were found in benzodiazepine receptors in the two strains. GABAB receptors were measured as 3H-baclofen binding in a crude synaptic membrane preparation and there was no difference between epileptic and control animals. Choline acetyltransferase, the synthetic enzyme for acetylcholine, and muscarinic receptor subtypes (M1 and M2), visualized respectively by an immunocytochemical procedure and binding autoradiography, did not differ in epileptic and normal rats. The data suggest an impairment of the 'GABAA system' in restricted brain regions of epileptic rats, due to a reduction of receptor beta 2-beta 3 subunits and coupling to benzodiazepine receptors despite the normal synthesis and location of the neurotransmitter.
Spreafico
R
R
Dept. of Neurophysiology, Istituto Neurologico C. Besta, Milan, Italy.
Mennini
T
T
Danober
L
L
Cagnotto
A
A
Regondi
M C
MC
Miari
A
A
De Blas
A
A
Vergnes
M
M
Avanzini
G
G
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D002540:Cerebral Cortex / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004832:Epilepsy, Absence / Q000235:genetics / Q000378:metabolism*; D005445:Flunitrazepam / Q000493:pharmacokinetics; D005968:Glutamate Decarboxylase / Q000378:metabolism; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism*; D018080:Receptors, GABA-B / Q000187:drug effects / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000187:drug effects; D013045:Species Specificity; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism; D013788:Thalamus / Q000378:metabolism
D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D011976:Receptors, Muscarinic; D005445:Flunitrazepam; D002795:Choline O-Acetyltransferase; D005968:Glutamate Decarboxylase; D000109:Acetylcholine