The Reorganization of Hippocampal NO-Ergic Synapses Is Associated with Increased Expression of Soluble Guanilyl Cyclase Immunoreactivity an CA1 Pyramidal Neurons in Temporal Lobe Epilepsy.
Abstract number :
1.247
Submission category :
Year :
2000
Submission ID :
1404
Source :
www.aesnet.org
Presentation date :
12/2/2000 12:00:00 AM
Published date :
Dec 1, 2000, 06:00 AM
Authors :
Joao P Leite, Antonio R Martins, Vera C Terra-Bustamante, Leila Chimelli, Gilberto De Nucci, Joao A Assirati, Ferid Murad, Univ of Sao Paulo Sch of Medicine, Ribeirao Preto, Brazil; Univ of Sao Paulo Sch of Medicine, Ribeirao Preto, Brunei; Institute of B
RATIONALE:_Several studies have pointed out that nitric oxide (NO) is implicated in a variety of functions, including the control of synaptic plasticity and sensory signaling. Among other effects, NO can activate soluble guanylyl cyclase (sGC), thus increasing cGMP production. Recent evidence from our laboratory suggests that hippocampi from mesial temporal lobe epilepsy patients exhibit a loss of brain NOS-immunoreactive (bNOS-IR) neurons and an abnormal innervation of the fascia dentata (FD) molecular layer. The present study was designed to investigate whether bNOS synaptic reorganization is associated with changes on sCG expression in hippocampi from patients with temporal lobe epilepsy. METHODS: Human hippocampi of patients with hippocampal sclerosis (HS, n=22) and extrahippocampal lesions (NONHS, n=4) were compared with autopsy controls (n=18) for FD bNOS-IR puncta densities, and sGC-IR in CA1 pyramidal cells. RESULTS:_Compared to autopsy controls and NONHS, HS hippocampi had significantly greater puncta densities in the FD inner and outer molecular layers (p<0.009 and p<0.003, respectively). Pyramidal cells sGC-IR were observed in both epileptic and control groups. However, the few pyramidal cells in the Sommer's sector of HS patients were significantly more stained than controls. Computerized densitometry showed that pyramidal cells mean gray values (?SD) were 139.4 ? 10.8 for the hs group, and 98.8 ? 7.2 for necropsy controls, (ANOVA, p<0.0001). CONCLUSIONS: The abnormal innervation of bNOS-IR terminals in the epileptic hippocampi was found to be associated with sGC upregulation in CA1 pyramidal neurons. Since the activity of the NOcGMP pathway does not obey the topographical constraints imposed to conventional synaptic transmitters, target cells can be stimulated even in regions with severe deafferentation. The plastic changes described here may thus contribute to hippocampal hyperexcitability. [Supported by CNPq, FAPESP and PRONEX - Brazil]