Abstract
Osteoblasts derived osteocalcin (OCN) is recently reported to be involved in dopaminergic neuronal development. As dopaminergic neuronal injury in the substantia nigra (SN) is a pathological hallmark of Parkinson’s disease (PD), we investigated whether OCN could exert protective effects on 6-hydroxydopamine (6-OHDA)-induced PD rat model. Our data showed that the OCN level in the cerebrospinal fluid (CSF) in PD rat models was significantly lower than that in controls. Intervention with OCN could improve the behavioral dysfunction in PD rat models and reduce the tyrosine hydroxylase (TH) loss in the nigrostriatal system. In addition, OCN could inhibit the astrocyte and microglia proliferation in the SN of PD rats. In vitro studies showed that OCN significantly ameliorated the neurotoxicity of 6-OHDA through the AKT/GSK3β signaling pathway. In summary, OCN plays a protective role against parkinsonian neurodegeneration in the PD rat model, suggesting a potential therapeutic use of OCN in PD.
Highlights
Parkinson’s disease (PD) is one of the most common neurodegenerative diseases characterized by cardinal movement disorders, including bradykinesia, tremor and rigidity (Postuma et al, 2015; Obeso et al, 2017), and its nonmotor symptoms, such as cognitive dysfunction, are increasingly recognized (Crowley et al, 2018)
To test the novel hypothesis that OCN exerts protective effects in PD, in the current study, we investigated whether intrastriatal (i.s.) injection or intraperitoneal (i.p.) injection of OCN could ameliorate the behavioral deficits in 6-hydroxydopamine (6-OHDA)-induced PD rat models and whether OCN treatment could reduce dopaminergic neuronal loss in the nigrostriatal pathway
Since AKT/GSK3β signal transduction impairment is believed to be associated with dopaminergic neuronal dysfunction in PD (Morissette et al, 2010; Chen et al, 2017), we explored whether the protective function of OCN
Summary
Parkinson’s disease (PD) is one of the most common neurodegenerative diseases characterized by cardinal movement disorders, including bradykinesia, tremor and rigidity (Postuma et al, 2015; Obeso et al, 2017), and its nonmotor symptoms, such as cognitive dysfunction, are increasingly recognized (Crowley et al, 2018). Dopaminergic neuronal degeneration, with the consequences of loss of dopaminergic neurons in the substantia nigra (SN) and depletion of dopamine (DA) in the striatum, are the main pathological events in PD (Maetzler and Berg, 2018). Since its first description 200 years ago, numerous efforts have been made to explore the underlying mechanisms of PD (Balestrino and Schapira, 2018) and to identify molecules inside (Parisiadou et al, 2014; Steinkellner et al, 2018) and outside of the brain (Weng et al, 2007; Chou et al, 2008; Guo et al, 2017) responsible for disease development or progression. Due to its complexity and heterogeneity in pathogenesis, there is a need to think about PD in new ways and find novel means to manage this debilitating disorder (Maetzler and Berg, 2018). The cross-talk between bone and brain was suggested by a series of works from Karsenty’s group revealing that bone-derived osteocalcin (OCN) is important for brain development (Obri et al, 2018)
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