Dietary Vitamin E as a Protective Factor for Parkinson's Disease: Clinical and Experimental Evidence.

Tommaso Schirinzi,Antonio Pisani,Giulia Di Lazzaro,Giuseppina Martella,Vito Luigi Colona,Paola Imbriani,Mariangela Pierantozzi,Mohammad Alwardat,Donatella Franco,Nicola Biagio Mercuri,Paola Sinibaldi Salimei

doi:10.3389/fneur.2019.00148

Abstract

Effective disease-modifying treatments are an urgent need for Parkinson's disease (PD). A putative successful strategy is to counteract oxidative stress, not only with synthetic compounds, but also with natural agents or dietary choices. Vitamin E, in particular, is a powerful antioxidant, commonly found in vegetables and other components of the diet. In this work, we performed a questionnaire based case-control study on 100 PD patients and 100 healthy controls. The analysis showed that a higher dietary intake of Vitamin E was inversely associated with PD occurrence independently from age and gender (OR = 1.022; 95% CI = 0.999–1.045; p < 0.05), though unrelated to clinical severity. Then, in order to provide a mechanistic explanation for such observation, we tested the effects of Vitamin E and other alimentary antioxidants in vitro, by utilizing the homozygous PTEN-induced kinase 1 knockout (PINK1−/−) mouse model of PD. PINK1−/− mice exhibit peculiar alterations of synaptic plasticity at corticostriatal synapses, consisting in the loss of both long-term potentiation (LTP) and long-term depression (LTD), in the absence of overt neurodegeneration. Chronic administration of Vitamin E (alpha-tocopherol and the water-soluble analog trolox) fully restored corticostriatal synaptic plasticity in PINK1−/− mice, suggestive of a specific protective action. Vitamin E might indeed compensate PINK1 haploinsufficiency and mitochondrial impairment, reverting some central steps of the pathogenic process. Altogether, both clinical and experimental findings suggest that Vitamin E could be a potential, useful agent for PD patients. These data, although preliminary, may encourage future confirmatory trials.

Highlights

Parkinson’s disease (PD) is a common neurodegenerative disorder, idiopathic, and multifactorial, mainly due to the loss of dopaminergic neurons in the Substantia Nigra pars compacta (SNpc) and to excessive brain accumulation of α-synuclein positive cytoplasmic Lewy bodies (LB)
PD and CTL were homogeneous in age and gender distribution; Vitamin E intake (VEI) was significantly higher in CTL (38.4 mg ± 17.8) than PD (31.6 mg ± 13.5; Statistical analysis was conducted on Log-transformed values, resulting p < 0.05)
(>5 observations for each experimental condition; T-test, p > 0.05; Table 2). Trolox fully rescued both the forms of synaptic plasticity either after acute or chronic administration (LTD protocol: 55.88 ± 6.01% of control; n = 16; t-test p < 0.05 Figure 1C; long-term potentiation (LTP) protocol: 175.30 ± 4.88% of control; n = 10; t-test p < 0.05 Figure 1D, Table 2); alpha-tochoperol restored in chronic conditions (LTD protocol: 56.9 ± 4.21% of control; n = 8; t-test p < 0.05; LTP protocol: 177.2 ± 6.36% of control; n = 6; t-test p < 0.05, Table 2). Both the clinical retrospective analysis and our electrophysiological experiments demonstrate that Vitamin E might exert potential beneficial effects in PD

Summary

Introduction

Parkinson’s disease (PD) is a common neurodegenerative disorder, idiopathic, and multifactorial, mainly due to the loss of dopaminergic neurons in the Substantia Nigra pars compacta (SNpc) and to excessive brain accumulation of α-synuclein positive cytoplasmic Lewy bodies (LB). Effective disease modifying treatments represent an unmet clinical need [1,2,3]. Successful neuroprotection may imply a combined approach against the different partners of neurodegeneration [4]. Since oxidative stress is a major player of the neurodegenerative process in PD, the modulation of redox balance has been extensively explored as a potential strategy to prevent neural death and disease progression. Different antioxidant agents are under investigation in several clinical trials [5,6,7,8,9]. An antioxidant-rich diet could represent a viable option to boost antioxidant pathways counteracting neurodegeneration

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Conclusion