title: BL-1023 improves behavior and neuronal survival in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-intoxicated mice.
abstract: The therapeutic potential of BL-1023, a chemical combination of L-3,4-dihydroxyphenylalanine (L-DOPA) and gamma-aminobutyric acid (GABA), was investigated in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxicated mice. Such animals exhibit nigrostriatal degeneration, characteristic of human Parkinson's disease. Drug was administered during and after the development of MPTP-induced nigrostriatal lesions followed by measures of motor function and behavior, surviving nigrostriatal dopaminergic neurons and termini, and striatal dopamine levels. When administered after lesion development, BL-1023 improved motor function of MPTP-mice as measured by rotarod, total floor and vertical plane movements, and stereotypic movements in open field activity tests compared to MPTP-mice without treatment. This also paralleled modest nigral dopaminergic neuronal protection. Such significant improvements in motor function, behaviors, and dopaminergic neuronal numbers were not seen when BL-1023 was administered during MPTP-induced lesion development. The data demonstrate select abilities of BL-1023 to increase dopaminergic neuronal survival and improve motor function in MPTP-mice.
authors.affiliation: Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, 985880 Nebraska Medical Center (DRC I 8008), Omaha, NE 68198-5880, USA.
authors.forename: J A L
authors.initials: JA
authors.lastname: Hutter-Saunders
authors.forename: L M
authors.initials: LM
authors.lastname: Kosloski
authors.forename: J M
authors.initials: JM
authors.lastname: McMillan
authors.forename: N
authors.initials: N
authors.lastname: Yotam
authors.forename: T
authors.initials: T
authors.lastname: Rinat
authors.forename: R L
authors.initials: RL
authors.lastname: Mosley
authors.forename: H E
authors.initials: HE
authors.lastname: Gendelman
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D004338:Drug Combinations; D007150:Immunohistochemistry; D007980:Levodopa / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000473:pathology; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: C559977:BL-1023; D004338:Drug Combinations; D018696:Neuroprotective Agents; D007980:Levodopa; D005680:gamma-Aminobutyric Acid