Alterations of the neocortical GABAergic system in the pilocarpine model of temporal lobe epilepsy: neuronal damage and immunocytochemical changes in chronic epileptic rats.
A wealth of previous studies reported pathological alterations in extrahippocampal regions in mesial temporal lobe epilepsy. Previous experimental findings have also demonstrated that the entorhinal cortex and the neocortex are damaged in different animal models of acute limbic seizures. The present study was aimed at verifying possible alterations in neocortical areas, and, in particular, structural changes of GABAergic interneurons in the sensorimotor cortex, in pilocarpine-induced chronic epilepsy in the rat. Series of sections were Nissl stained and processed for immunocytochemistry using antibodies that recognize nonphosphorylated neurofilament (SMI311), glial fibrillary acidic protein (GFAP), the calcium-binding protein parvalbumin (PV) which is expressed by a subset of cortical GABAergic neurons, the GABA transporter (GAT1), and isoform 65 of glutamic acid decarboxylase (GAD65), the GABA synthetic enzyme. Epileptic rats showed decreased cortical thickness, and diffuse gliosis was observed with GFAP antibody. Neurofilament alterations were also detected in sections processed using SMI311 antiserum. In addition, a diffuse decrease of PV, GAD65, and GAT1 immunoreactivity was observed in the sensorimotor cortex. Altered expression of PV, GAD65, and GAT1 pointed out specific neocortical disturbances in GABAergic inhibition, which could play a crucial role in seizure generation and expression. Thus, the present findings indicate that damage of GABAergic interneurons could be strictly associated with neocortical hyperexcitability in temporal lobe epilepsy.
Laboratório de Neurologia Experimental, Universidade Federal de São Paulo-Escola Paulista de Medicina, São Paulo, Brazil. valotta.nexp@epm.br
A V
AV
Silva
E R G
ER
Sanabria
E A
EA
Cavalheiro
R
R
Spreafico
D000818:Animals; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D007150:Immunohistochemistry; D008297:Male; D019579:Neocortex / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology*; D010862:Pilocarpine; D051381:Rats; D017208:Rats, Wistar; D005680:gamma-Aminobutyric Acid / Q000032:analysis / Q000502:physiology*
D010862:Pilocarpine; D005680:gamma-Aminobutyric Acid