title: Activin A Inhibits MPTP and LPS-Induced Increases in Inflammatory Cell Populations and Loss of Dopamine Neurons in the Mouse Midbrain In Vivo.
abstract: Parkinson's disease is a chronic neurodegenerative disease characterized by a significant loss of dopaminergic neurons within the substantia nigra pars compacta region and a subsequent loss of dopamine within the striatum. A promising avenue of research has been the administration of growth factors to promote the survival of remaining midbrain neurons, although the mechanism by which they provide neuroprotection is not understood. Activin A, a member of the transforming growth factor β superfamily, has been shown to be a potent anti-inflammatory following acute brain injury and has been demonstrated to play a role in the neuroprotection of midbrain neurons against MPP+-induced degeneration in vitro. We hypothesized that activin A may offer similar anti-inflammatory and neuroprotective effects in in vivo mouse models of Parkinson's disease. We found that activin A significantly attenuated the inflammatory response induced by both MPTP and intranigral administration of lipopolysaccharide in C57BL/6 mice. We found that administration of activin A promoted survival of dopaminergic and total neuron populations in the pars compacta region both 8 days and 8 weeks after MPTP-induced degeneration. Surprisingly, no corresponding protection of striatal dopamine levels was found. Furthermore, activin A failed to protect against loss of striatal dopamine transporter expression in the striatum, suggesting the neuroprotective action of activin A may be localized to the substantia nigra. Together, these results provide the first evidence that activin A exerts potent neuroprotection and anti-inflammatory effects in the MPTP and lipopolysaccharide mouse models of Parkinson's disease.
authors.affiliation: Neuroscience Department, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.
authors.forename: Sandy
authors.initials: S
authors.lastname: Stayte
authors.affiliation: Neuroscience Department, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.
authors.forename: Peggy
authors.initials: P
authors.lastname: Rentsch
authors.affiliation: FH Krems University of Applied Science, Krems, Austria.
authors.forename: Anna R
authors.initials: AR
authors.lastname: Tröscher
authors.affiliation: FH Krems University of Applied Science, Krems, Austria.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Bamberger
authors.affiliation: Pharmacology Department, Bosch Institute, Sydney Medical School, The University of Sydney, Sydney, Australia.
authors.forename: Kong M
authors.initials: KM
authors.lastname: Li
authors.affiliation: Neuroscience Department, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.|School of Life Sciences, University of Technology Sydney, Sydney, Australia.
authors.forename: Bryce
authors.initials: B
authors.lastname: Vissel
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D028341:Activins / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002470:Cell Survival / Q000187:drug effects*; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000473:pathology; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008070:Lipopolysaccharides; D020267:MPTP Poisoning / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008636:Mesencephalon / Q000187:drug effects* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D008070:Lipopolysaccharides; C422405:activin A; D028341:Activins; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine