Abstract
Parkinson’s disease (PD) is a chronic neurodegenerative disease characterized by a significant loss of dopaminergic neurons within the substantia nigra pars compacta (SNpc) and a subsequent loss of dopamine (DA) within the striatum. Despite advances in the development of pharmacological therapies that are effective at alleviating the symptoms of PD, the search for therapeutic treatments that halt or slow the underlying nigral degeneration remains a particular challenge. Activin A, a member of the transforming growth factor β superfamily, has been shown to play a role in the neuroprotection of midbrain neurons against 6-hydroxydopamine (6-OHDA) in vitro, suggesting that activin A may offer similar neuroprotective effects in in vivo models of PD. Using robust stereological methods, we found that intrastriatal injections of 6-OHDA results in a significant loss of both TH positive and NeuN positive populations in the SNpc at 1, 2, and 3 weeks post-lesioning in drug naïve mice. Exogenous application of activin A for 7 days, beginning the day prior to 6-OHDA administration, resulted in a significant survival of both dopaminergic and total neuron numbers in the SNpc against 6-OHDA-induced toxicity. However, we found no corresponding protection of striatal DA or dopamine transporter (DAT) expression levels in animals receiving activin A compared to vehicle controls. These results provide the first evidence that activin A exerts potent neuroprotection in a mouse model of PD, however this neuroprotection may be localized to the midbrain.
Highlights
Parkinson’s disease (PD) is a chronic neurodegenerative disease characterized by significant loss of dopaminergic neurons within the substantia nigra pars compacta (SNpc) and a subsequent loss of dopamine (DA) within the striatum
As we demonstrated that activin A treatment is able to protect against both dopaminergic and total neuron loss induced by 6-OHDA toxicity, it would be reasonable to presume that activin A treatment would result in a concurrent protection of striatal DA levels
Despite decades of preclinical and clinical research, the current pharmacological therapies for PD remain ineffective in the long term and are unable to halt ongoing nigrostriatal degeneration
Summary
Parkinson’s disease (PD) is a chronic neurodegenerative disease characterized by significant loss of dopaminergic neurons within the substantia nigra pars compacta (SNpc) and a subsequent loss of dopamine (DA) within the striatum. While the use of levodopa (L-Dopa) has provided considerable benefits in the treatment of the motor symptoms, one of the remaining. Activin A Is Neuroprotective in the 6-OHDA Mouse Model collection and analysis, decision to publish, or preparation of the manuscript
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