Functional and histological consequences of quinolinic and kainic acid-induced seizures on hippocampal somatostatin neurons.
Changes in endogenous somatostatin after quinolinic and kainic acids were investigated by measuring somatostatin-like peaks by in vivo voltammetry and by assessing the distribution of somatostatin-positive neurons by immunocytochemistry. Kainic acid (0.19 nmol/0.5 microliter) or quinolinic acid (120 nmol/0.5 microliter) in doses inducing comparable electroencephalographic seizure patterns, were injected into the hippocampus of freely moving rats. Somatostatin-like peaks were measured every 6 min for 3 h by a carbon fiber electrode implanted in the proximity of the injection needle. Kainic acid kept somatostatin-like peaks significantly higher than saline from 48 min after the injection till the end of the recording. Somatostatin-like peaks were dramatically elevated by quinolinic acid, reaching a maximum of 482% 60 min after the injection. Three days later, administration of kainic acid resulted in selective degeneration of CA3 pyramidal neurons but did not affect the number of somatostatin-positive cells, while quinolinic acid induced cell loss in all pyramidal layers and complete degeneration of somatostatin-positive cells in the whole hippocampus. Thus, the quantitative difference in somatostatin release in response to doses of kainic and quinolinic acids inducing comparable electroencephalographic seizure patterns was reflected in a substantial difference in the neurodegenerative consequences. In both models, the release of somatostatin in response to seizures may be interpreted as a "defense" mechanism aimed at reducing the spread of excitation in the tissue.
Istituto di Ricerche Farmacologiche, Mario Negri, Milano, Italy.
A
A
Manfridi
G L
GL
Forloni
A
A
Vezzani
F
F
Fodritto
M G
MG
De Simoni
D000818:Animals; D002470:Cell Survival; D003543:Cysteamine / Q000494:pharmacology; D004569:Electroencephalography; D004827:Epilepsy / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology*; D007608:Kainic Acid / Q000633:toxicity*; D008297:Male; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D017378:Quinolinic Acid; D011805:Quinolinic Acids / Q000633:toxicity*; D051381:Rats; D013004:Somatostatin / Q000378:metabolism*
D011805:Quinolinic Acids; D013004:Somatostatin; D003543:Cysteamine; D017378:Quinolinic Acid; D007608:Kainic Acid