ly-344864 and Parkinson-Disease

Parkinson's disease is characterized by progressive decline in motor function due to degeneration of nigrostriatal dopaminergic neurons, as well as other deficits including cognitive impairment and behavioural abnormalities. Mitochondrial dysfunction, leading to loss of ATP-dependent cellular functions, calcium overload, excitotoxicity and oxidative stress, is implicated in the pathophysiology of Parkinson's disease. Using the 5-HT. Male C57BL/6 mice underwent bilateral intrastriatal 6-hydroxydopamine or saline injections and daily treatment with 2 mg·kg. Increased mitochondrial DNA content and nuclear- and mitochondrial-encoded mRNA and protein expression was observed in specific brain regions of LY344864-treated naïve and lesioned mice, indicating augmented MB. LY344864 attenuated TH-ir loss in the striatum and substantia nigra compared to vehicle-treated lesioned animals. LY344864 treatment also increased locomotor activity in 6-hydroxydopamine lesioned mice, while vehicle treatment had no effect.. These data revealed that LY344864-induced MB attenuates dopaminergic neuron loss and improves behavioural endpoints in this model. We suggest that stimulating MB may be beneficial for the treatment of Parkinson's disease and that the 5-HT

Topics: Animals; Carbazoles; Corpus Striatum; Fluorobenzenes; Locomotion; Male; Mice; Mitochondria; Organelle Biogenesis; Oxidopamine; Parkinson Disease; Receptor, Serotonin, 5-HT1F; Receptors, Serotonin; Substantia Nigra; Tyrosine 3-Monooxygenase