Deficit in hippocampal long-term potentiation in monosodium glutamate-treated rats.

Rats subjected to monosodium glutamate (MSG) administration during the neonatal period present chronic neuroendocrine dysfunction associated with marked cognitive deficits. Long-term potentiation (LTP) in the hippocampus provides a model suited for the study of mammalian brain plasticity and memory formation. In the present work, we used the LTP protocol to investigate the synaptic plasticity in the hippocampal CA1 area of adult rats subjected to MSG treatment during the first 10 days of life. Synaptic transmission in CA1 area was analyzed using extracellular field recordings in response to Schaffer's collateral fiber stimulation in hippocampal slices. Animals injected with MSG exhibited a dramatic decrement of LTP field excitatory postsynaptic potentials (fEPSPs) compared to control group. Analysis of percent enhancement of fEPSP slope at 2 min after high frequency stimulation (HFS) increased by 189.3 +/- 33.2% in slices from control rats and 129.45 +/- 18.5% (p < 0.01) in slices from MSG-treated rats. Additionally, MSG-treated animals failed to maintain or consolidate LTP as revealed by a significant reduction in fEPSP slope enhancement over time after HFS. The mean fEPSP slope, 60 min after HFS, was 154.28 +/- 21% of the average baseline slope in control slices versus only 124.4 +/- 15% in MSG-treated rats (p < 0.01). At 90 min after HFS, slices from controls reached a potentiation of 44.5 +/- 2.9%, whereas the MSG group displayed an overall response enhancement of 17.65 +/- 2.7% of basal levels (p < 0.01). These findings indicate that MSG-treated rats display a chronic impairment of CA1 synaptic plasticity.

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.

Evidence that ATP participates in the pathophysiology of pilocarpine-induced temporal lobe epilepsy: fluorimetric, immunohistochemical, and Western blot studies.

PURPOSE: This study was performed to study the role of adenosine triphosphate (ATP) in the brain of pilocarpine-induced chronic epileptic rats. METHODS: ATP-mediated changes in intracellular calcium were studied by the fura-2 method. Immunohistochemistry and Western blotting methods were used to localize and quantify P2X7 receptors in these animals. RESULTS: The fluorimetric study in chronic rats revealed a biphasic response indicating the presence of P2X7 receptors. The Western blotting study showed an increase of 80% of P2X7 expression in chronic rats compared with the control group. P2X7 immunoreactivity resembled mossy fiber sprouting at the dentate gyrus of epileptic animals. CONCLUSIONS: These results suggest that purinergic receptors may participate in the pathophysiology of temporal lobe epilepsy.