Evaluating Dose- and Time-Dependent Effects of Vitamin C Treatment on a Parkinson’s Disease Fly Model

Abstract

Parkinson's disease (PD) is a common neurodegenerative disorder and characterized by progressive locomotive defects and loss of dopaminergic neurons (DA neuron). Currently, there is no potent therapy to cure PD, and the medications merely support to control the symptoms. It is difficult to develop an effective treatment, since the PD onset mechanism of PD is still unclear. Oxidative stress is considered as a major cause of neurodegenerative diseases, and there is increasing evidence for the association between PD and oxidative stress. Therefore, antioxidant treatment may be a promising therapy for PD. Drosophila with knockdown of dUCH, a homolog of UCH-L1 which is a PD-related gene, exhibited PD-like phenotypes including progressive locomotive impairments and DA neuron degeneration. Moreover, knockdown of dUCH led to elevated level of ROS. Thus, dUCH knockdown flies can be used as a model for screening of potential antioxidants for treating PD. Previous studies demonstrated that curcumin at 1 mM and vitamin C at 0.5 mM could improve PD-like phenotypes induced by this knockdown. With the purpose of further investigating the efficiency of vitamin C in PD treatment, we used dUCH knockdown Drosophila model to examine the dose- and time-dependent effects of vitamin C on PD-like phenotypes. The results showed that although vitamin C exerted neuroprotective effects, high doses of vitamin C and long-term treatment with this antioxidant also resulted in side effects on physiology. It is suggested that dose-dependent effects of vitamin C should be considered when used for treating PD.

Enhanced accumulation of reduced glutathione by Scopoletin improves survivability of dopaminergic neurons in Parkinson’s model

“…A large number of antioxidant based strategies focusing on ascorbic acid, deferoxamine, cucurmin etc has been investigated for management of the PD symptoms but without any translatable benefits 47 , 48 ; thus requiring elucidation of better alternatives with robust antioxidant capabilities to promote neuronal health in PD. Natural derivatives have been increasingly appreciated for their potency in prevention and management of neurodegenerative diseases 35 , 49 , 50 .…”

Antioxidant Therapies for Neuroprotection—A Review

“…Vitamin C, also known as ascorbic acid, is an essential water-soluble antioxidant that performs many important functions in the body [96,105]. It is considered as an ideal antioxidant as it is characterized by a low reduction potential that allows for its reaction with various ROS [106].…”

“…In the body, vitamin C is involved in many physiological processes, such as the formation of collagen as a co-factor [108] and the conversion of cholesterol to bile acids [109]. Moreover, vitamin C is present in the brain in high concentrations, participating in processes such as neuronal differentiation, maturation, and survival, dopamine and norepinephrine biosynthesis, neurotransmission modulation, and neuronal protection against glutamate toxicity [105,110]. However, by contrast to most mammals that produce vitamin C from glucose in the liver, humans cannot synthesize it due to the lack of L-gulonolactone enzyme and are dependent on dietary sources [105,111].…”

“…Several studies have shown that vitamin C deficiencies could be related to neurodegenerative disorders, such as Parkinson’s, Alzheimer’s, and Huntington’s diseases and amyotrophic sclerosis [105,110]. Particularly, a clinical study showed that the administration of vitamin C and/or E supplements, resulted in a decrease of the risk of cognitive decline in older persons ≥65 years old [112].…”

“…Therefore, it can provide a potential treatment for stress-related cognitive decline [113]. Moreover, a study performed on a Drosophila model with Parkinson’s disease-like phenotypes caused by the knockdown of the Parkinson’s disease-related gene homologue dUCH, which are characterized by locomotive impairments and neurodegeneration, showed that the administration of vitamin C at high doses leads to significant side effects, and long-term treatment could prevent the degeneration of dopaminergic neurons [105]. The effect of vitamin C in lipopolysaccharide-induced cognitive impairment as a model for neuroinflammatory cognitive dysfunction was also investigated.…”