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Neuroprotective effects of (+/-)-kavain in the MPTP mouse model of Parkinson's disease.
Synapse. 2001 Apr; 40(1):47-54.S

Abstract

This is the first study to investigate the potential protective effects of the lipophilic kavapyrone (+/-)-kavain in the experimental MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) model of Parkinson's disease (PD). Male C57BL/6 mice were treated with (+/-)-kavain (50, 100, or 200 mg/kg i.p.) or vehicle 60 min before and 60 min after a single administration of MPTP (30 mg/kg s.c.) or saline, respectively. Mice were sacrificed after 7 days and the neostriatum was analyzed for dopamine and its metabolites using HPLC with electrochemical detection. Furthermore, nigral sections were processed for tyrosine hydroxylase (TH) immunocytochemistry. To determine the effects of (+/-)-kavain (200 mg/kg) on MPTP metabolism, HPLC analysis of striatal MPP(+) (1-methyl-4-phenylpyridinium) levels was performed. MPTP treatment alone led to a significant depletion of striatal dopamine levels to 12.61% of saline controls. The lower dosages of (+/-)-kavain (50 and 100 mg/kg) showed only a nonsignificant attenuation of MPTP-induced dopamine depletion, but a high dosage of (+/-)-kavain (200 mg/kg) significantly antagonized the dopamine depletion to 58.93% of saline control values. Remarkably, the MPTP-induced decrease of TH-immunoreactivity as well as the loss of nigral neurons was completely prevented by (+/-)-kavain (200 mg/kg). Striatal MPP(+) levels were not altered by (+/-)-kavain treatment. In conclusion, we found that MPTP metabolism was not influenced by (+/-)-kavain and postulate the antiglutamatergic effects of (+/-)-kavain for its protective effects against MPTP toxicity. (+/-)-Kavain may be a novel candidate for further preclinical studies in animal models of PD and other disorders with glutamatergic overactivity.

Authors+Show Affiliations

Institute of Pharmacology and Toxicology, Faculty of Pharmacy, University of Marburg, Marburg, Germany.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11170221

Citation

Schmidt, N, and B Ferger. "Neuroprotective Effects of (+/-)-kavain in the MPTP Mouse Model of Parkinson's Disease." Synapse (New York, N.Y.), vol. 40, no. 1, 2001, pp. 47-54.
Schmidt N, Ferger B. Neuroprotective effects of (+/-)-kavain in the MPTP mouse model of Parkinson's disease. Synapse. 2001;40(1):47-54.
Schmidt, N., & Ferger, B. (2001). Neuroprotective effects of (+/-)-kavain in the MPTP mouse model of Parkinson's disease. Synapse (New York, N.Y.), 40(1), 47-54.
Schmidt N, Ferger B. Neuroprotective Effects of (+/-)-kavain in the MPTP Mouse Model of Parkinson's Disease. Synapse. 2001;40(1):47-54. PubMed PMID: 11170221.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neuroprotective effects of (+/-)-kavain in the MPTP mouse model of Parkinson's disease. AU - Schmidt,N, AU - Ferger,B, PY - 2001/2/15/pubmed PY - 2001/5/5/medline PY - 2001/2/15/entrez SP - 47 EP - 54 JF - Synapse (New York, N.Y.) JO - Synapse VL - 40 IS - 1 N2 - This is the first study to investigate the potential protective effects of the lipophilic kavapyrone (+/-)-kavain in the experimental MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) model of Parkinson's disease (PD). Male C57BL/6 mice were treated with (+/-)-kavain (50, 100, or 200 mg/kg i.p.) or vehicle 60 min before and 60 min after a single administration of MPTP (30 mg/kg s.c.) or saline, respectively. Mice were sacrificed after 7 days and the neostriatum was analyzed for dopamine and its metabolites using HPLC with electrochemical detection. Furthermore, nigral sections were processed for tyrosine hydroxylase (TH) immunocytochemistry. To determine the effects of (+/-)-kavain (200 mg/kg) on MPTP metabolism, HPLC analysis of striatal MPP(+) (1-methyl-4-phenylpyridinium) levels was performed. MPTP treatment alone led to a significant depletion of striatal dopamine levels to 12.61% of saline controls. The lower dosages of (+/-)-kavain (50 and 100 mg/kg) showed only a nonsignificant attenuation of MPTP-induced dopamine depletion, but a high dosage of (+/-)-kavain (200 mg/kg) significantly antagonized the dopamine depletion to 58.93% of saline control values. Remarkably, the MPTP-induced decrease of TH-immunoreactivity as well as the loss of nigral neurons was completely prevented by (+/-)-kavain (200 mg/kg). Striatal MPP(+) levels were not altered by (+/-)-kavain treatment. In conclusion, we found that MPTP metabolism was not influenced by (+/-)-kavain and postulate the antiglutamatergic effects of (+/-)-kavain for its protective effects against MPTP toxicity. (+/-)-Kavain may be a novel candidate for further preclinical studies in animal models of PD and other disorders with glutamatergic overactivity. SN - 0887-4476 UR - https://www.unboundmedicine.com/medline/citation/11170221/Neuroprotective_effects_of__+/___kavain_in_the_MPTP_mouse_model_of_Parkinson's_disease_ DB - PRIME DP - Unbound Medicine ER -