The Class I Metabotropic Glutamate Receptor (mGluR) Antagonist, 1-Aminoindan-1,5-Dicarboxylic Acid Prevents Neuronal Loss and Limits Functional Changes in the Kainic Acid Model.
Abstract number :
1.153
Submission category :
Year :
2000
Submission ID :
3168
Source :
www.aesnet.org
Presentation date :
12/2/2000 12:00:00 AM
Published date :
Dec 1, 2000, 06:00 AM
Authors :
Martine Emond, Sebastien Meilleur, Caterina Psaropoulou, Lionel Carmant, Ste-Justine Hosp, Montreal, PQ, Canada.
RATIONALE: Intraperitoneal injections of kainic acid (KA) lead to chronic recurrent seizures, loss of hippocampal memory functions, and temporal lobe sclerosis. It is considered a model to study temporal lobe epilepsy. We showed that 1-aminoindan-1,5-dicarboxylic acid (AIDA) limits severity of recurrent seizures and memory loss. The present study was undertaken to evaluate if these beneficial effects were associated with preservation of anatomical landmarks and electrophysiological properties. METHODS: Rats were injected at P20 and P30 with either KA (8,0 mg/kg), AIDA (1,8mg/kg) or KA+AIDA (n=5/group). Controls received AIDA alone or saline. Initial and recurrent seizures were daily monitored by video. Morphological and electrophysiological changes were assessed 30 days after the injection. Cresyl violet staining was used to determine extent and location of neuronal loss, whereas occurrence of apoptosis was verified using the TUNEL method. Extracellular recordings were performed in the CA3 area of hippocampal slices in control solution (CS) and in the presence of the GABAA antagonist bicuculline (BMI) 10? M. RESULTS: At P30, the KA group showed a significant loss of pyramidal cells in layer CA3 as well as of hilar neurons. In area CA1, we found a decreased in cell density in the oriens/alveus layer. This was not observed in the KA+AIDA, AIDA and saline groups. At P20, these changes were not as marked. Maximal fEPSP amplitude, duration and number of population spikes (PS) were similar in all subgroups from animals injected at P20. PS duration and latency were consistently shorter in KA treated animals than in other groups, but this did not reach statistical significance. Also, amplitude of the PS was significantly lower in KA, but not in KA+AIDA, compared to controls in both CS and BMI (p? 0.05)._ CONCLUSIONS: : The metabotropic antagonist AIDA can reverse some of the long-term effects of the kainate-induced convulsions in the juvenile rat. Supported by Savoy Foundation for Epilepsy, NSERC and Ste-Justine Research Center.