Intervention with 7,8-dihydroxyflavone blocks further striatal terminal loss and restores motor deficits in a progressive mouse model of Parkinson’s disease

• Published in: Neuroscience 2015-04, Vol.290, p.454-471
• Main Authors: Sconce, M.D, Churchill, M.J, Moore, C, Meshul, C.K
• Format: Article
• Language: English
• Subjects: 7,8-dihydroxyflavone; Animals; Antiparkinson Agents - pharmacology; collateral sprouting; Corpus Striatum - drug effects; Corpus Striatum - pathology; Corpus Striatum - physiopathology; Flavones - pharmacology; Forelimb - drug effects; Forelimb - physiopathology; Intracellular Signaling Peptides and Proteins - metabolism; Male; Mice, Inbred C57BL; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - metabolism; Motor Activity - drug effects; Motor Activity - physiology; motor behavior; mouse model; MPTP; MPTP Poisoning - drug therapy; MPTP Poisoning - pathology; MPTP Poisoning - physiopathology; Neurology; Parkinson’s disease; Phosphorylation - drug effects; Random Allocation; Receptor, trkB - metabolism; Substantia Nigra - drug effects; Substantia Nigra - pathology; Substantia Nigra - physiopathology; Tyrosine 3-Monooxygenase - metabolism
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2014.12.080

Highlights • 7,8-DHF intervention blocks further loss of TH within the dorsolateral striatum in a progressive MPTP mouse model of PD. • Intervention with 7,8-DHF did not prevent further loss of TH-labeled neurons within the SNpc. • Mice administered 7,8-DHF showed an increase in SCG10 levels in the dorsolateral striatum, providing evidence for sprouting. • 7,8-DHF crosses the BBB and activates the MAPK pathway within the dorsolateral striatum even with continued MPTP treatment. • Behavioral deficits were recovered in animals administered 7,8-DHF despite 4 weeks of MPTP administration.