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A novel neurotrophic factor protects rat brain against a striatal neurotoxin and improves locomotion when administered to the damaged brain, according to a new study. Mesencephalic astrocyte-derived neurotrophic factor (MANF) is expressed in the vertebrate striatum and is upregulated in cerebral ischemia. To test its potential in PD, investigators injected various doses into the striatum of rats either before or after unilateral lesioning with 6-OHDA, a common model of PD, in which amphetamine-induced rotation is used to monitor damage to the striatum. When MANF was injected 6 hours before lesioning, rotation was reduced significantly compared to vehicle-treated rats when measured at 4 weeks post-lesion, though not at 2 weeks. The dose-response curve was bell-shaped, with 10 micrograms providing better response than either higher or lower doses, a phenomenon also seen with other neurotrophic factors. MANF given 4 weeks after lesioning reduced the cumulative number of amphetamine-induced rotations over time, and was superior to GDNF in this measure. GDNF is a neurotrophic factor that has produced mixed results in clinical trials in PD. The distribution volume for a single injection of MANF was larger than that for GDNF. Both MANF and GDNF slowed the loss of TH+ cells in the striatum compared to vehicle at 4 weeks after lesioning, though neither altered the density of TH+ fibers. "Our results suggest that MANF reduces amphetamine-induced turning behavior and protects dopaminergic neurons and striatal axons at least as well as GDNF," the authors conclude. "Because MANF readily diffuses in the striatum in rats, it may do the same in human brain and be beneficial for the treatment of parkinsonian patients." Mesencephalic astrocyte-derived neurotrophic factor is neurorestorative in rat model of Parkinson's disease MJ Voutilainen, S Back, E Porsti, L Toppinen, L Lindgren, P Lindholm, J Peranen, M Saama, RK Tuominen J Neurosci 2009;29:9651-9659 ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn