GM1 ganglioside attenuates the behavioral deficits but not the granule cell damage produced by intradentate colchicine.
Bilateral injection of 3.5 micrograms of colchicine into the dentate gyrus produced hyperactivity, impaired retention of a passive avoidance task, and enhanced the motor stimulant effects of a dopaminergic agonist (apomorphine) and the analgesic effects of morphine. In contrast, there was no alteration in scopolamine-induced hyperactivity. These effects were associated with a decrease in the thickness of the granule cell layer in both the superior and inferior blade of the dentate gyrus and a coincident decrease in the size of the overlying dentate molecular layer. Intraperitoneal injection of monosialoganglioside GM1 (30 mg/kg) beginning 3 days prior to surgery and continuing for 25 days following surgery appeared to limit the extent and duration of these behavioral effects. GM1 facilitated recovery of motor activity and attenuated the impaired retention of the passive avoidance task and the alterations in pharmacological sensitivity following intradentate injection of colchicine. Despite the facilitative effects of GM1 on behavior histological analysis of the hippocampus did not reveal a protective effect of this compound on colchicine-induced granule cell destruction. The results of these studies suggest that intradentate injection of colchicine is a useful model of human diseases where only restricted populations of neurons are damaged. Furthermore, these studies indicate that the use of monosialoganglioside GM1 might be a useful primary or adjunct approach to the treatment of neurodegenerative disorders and their behavioral sequelae.
Walsh
T J
TJ
Department of Psychology, Rutgers University, New Brunswick, NJ 08903.
Emerich
D F
DF
Schmechel
D E
DE
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D003078:Colchicine / Q000494:pharmacology*; D005677:G(M1) Ganglioside / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008568:Memory / Q000502:physiology*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344; D012153:Retention, Psychology / Q000187:drug effects / Q000502:physiology*; D012601:Scopolamine / Q000494:pharmacology
D005677:G(M1) Ganglioside; D012601:Scopolamine; D001058:Apomorphine; D003078:Colchicine