Serotonin may have neurotoxic properties.
Serotonin (5HT), a major platelet secretory product, has been shown to suppress CNS function in vivo. As part of an ongoing project to study interactions between neuron and platelet, we used organotypic explant cultures of rat spinal cord to study if 5HT had a morphologically demonstrable neurotoxic effect. The results suggest that serotonin may be neurotoxic, and that this effect may be prevented by ketanserin, a specific 5HT2 antagonist. Related experiments, using acetylcholinesterase (AChE) enzyme activity as a biochemical parameter, indicate that 5HT hastens the decline of enzyme activity. The concentrations of 5HT at which neurotoxicity was demonstrated were comparable to the calculated 5HT concentration potentially present in the vicinity of an acute cerebral thrombus. These findings could provide new insight into the mechanism of ischemic neuronal injury.
Joseph
R
R
Department of Neurology, Henry Ford Hospital, Detroit, MI 48202.
Tsering
C
C
Grunfeld
S
S
Welch
K M
KM
D000110:Acetylcholinesterase / Q000032:analysis; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D002452:Cell Count; D016923:Cell Death; D004305:Dose-Response Relationship, Drug; D002542:Intracranial Embolism and Thrombosis / Q000503:physiopathology; D007650:Ketanserin / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000032:analysis; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology; D051381:Rats; D012701:Serotonin / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity*; D013116:Spinal Cord / Q000187:drug effects*
D009419:Nerve Tissue Proteins; D012701:Serotonin; D007650:Ketanserin; D000110:Acetylcholinesterase