Abstract
Parkinson's disease (PD) is accompanied by motor impairments due to the loss of dopaminergic neurons in the nigrostriatal pathway. Levodopa (L-dopa) has been the gold standard therapy for PD since the 1960s; however, its neurotoxic features accelerate PD progression through auto-oxidation or the induction of dyskinetic movements. Ukgansan (UGS) is a well-known prescription for treating PD in traditional medicines of East Asia, and its anti-PD function has been experimentally evaluated. The present study investigated whether UGS attenuates (1) motor dysfunction and dopaminergic neuronal damage when co-treated with L-dopa and (2) L-dopa-induced dyskinesia (LID) in 6-hydroxydopamine (6-OHDA)-induced PD mice. Although L-dopa was found to reduce motor dysfunctions, it failed to decrease the dopaminergic neuronal damage and increased the expression of dopamine receptor 1 (D1R) and 2 (D2R) in the 6-OHDA-injected mouse striatum. Co-treatment with UGS resulted in normal striatal histology and ameliorated motor impairments. In addition, UGS suppressed the dyskinesia induced by chronic L-dopa treatment while restoring the dopaminergic neurons in the striatum. For the underlying mechanism, UGS reduced the overexpression of D1R-related signaling proteins, such as phosphorylated extracellular signal-regulated kinase, ΔFosB, and c-fos in the striatum. Overall, the results suggest that the effect of UGS could be complementary to L-dopa by ameliorating motor dysfunction, restoring the dopaminergic neurons, and suppressing the dyskinetic movements in PD.
Highlights
Parkinson’s disease (PD), one of the most typical neurodegenerative diseases, accounts for 1–2% of the population over 65 years of age, presenting motor dysfunctions such as bradykinesia, tremor, rigidity, and postural instability (Jankovic, 2008)
UGS Reduced the Dopaminergic Neuronal Damage Induced by 6-OHDA in the Mouse ST and substantia nigra pars compacta (SNpc) When Co-treated With L-Dopa, Reduction did not Occur in the L-Dopa Only Treatment
We investigated whether (1) the combined treatment of UGS with L-dopa attenuates motor functions in 6-OHDA-induced parkinsonian mice compared to L-dopa single treatment and whether (2) UGS ameliorates dyskinesia in response to chronic administration of L-dopa
Summary
Parkinson’s disease (PD), one of the most typical neurodegenerative diseases, accounts for 1–2% of the population over 65 years of age, presenting motor dysfunctions such as bradykinesia, tremor, rigidity, and postural instability (Jankovic, 2008). These manifestations are caused by the lack of dopamine via loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the striatum (ST) (De Lau and Breteler, 2006). There are some critical limitations of L-dopa since its effects are merely symptomatic and not as fundamental One such limitation is that L-dopa may accelerate dopaminergic neuronal death during the progression of PD (Fahn et al, 2004). Though the mechanisms of LID have not been clearly revealed, it is closely related with the hyperactivation of the dopamine receptor 1 (D1R)-related signaling pathway in striatal projection neurons (Feyder et al, 2011; Fieblinger et al, 2014)
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