Protective effects of cortistatin (CST-14) against kainate-induced neurotoxicity in rat brain.
Cortistatin (CST-14) is a recently discovered endogenous peptide which shares similarity to somatostatin and binds to somatostatin receptors. In this study, we show that CST-14 exhibits anticonvulsive and neuroprotective effects in rats. Injection of rats with kainic acid (KA; 10 mg/kg; i.p.) generated a strong seizure activity which was attenuated by the i.c.v. application of 1 and 10 nmol CST-14 when given 10 min before KA. Moreover, 3 days after KA injection, a marked loss of neurons in cortex and hippocampus of rats was observed which was inhibited by pretreatment with CST-14. An immunohistochemical analysis using specific antibodies revealed that KA reduced immunoactive sst2A and sst3 somatostatin receptors in the hippocampus-an effect which was largely prevented by pretreatment with CST-14. Superfusion of hippocampal slices with CST-14 also reduced the stimulated release of 3H-d-aspartate. We conclude that CST-14 exerts neuroprotective effects by binding to somatostatin receptors which in turn leads to a reduced release of excitotoxic neurotransmitters.
Braun
H
H
Department of Pharmacology and Toxicology, Otto-von-Guericke University, Leipziger Str.44, D-39120, Magdeburg, Germany.
Schulz
S
S
Becker
A
A
Schröder
H
H
Höllt
V
V
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D002404:Catheterization; D002452:Cell Count / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D007608:Kainic Acid / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D009474:Neurons / Q000187:drug effects; D009479:Neuropeptides / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017481:Receptors, Somatostatin / Q000032:analysis / Q000096:biosynthesis; D012640:Seizures / Q000188:drug therapy / Q000517:prevention & control
D009479:Neuropeptides; D017481:Receptors, Somatostatin; C099323:cortistatin; C103631:somatostatin receptor 3; C106140:somatostatin receptor sst2A; D007608:Kainic Acid