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Implication of vitamin A in neuroprotection of dopaminergic neurons in a rat model of Parkinson's disease

Abstract : Parkinson’s disease (PD) is a brain disease caused by a loss of dopaminergic neurons in the substantia nigra pars compacta (SNc), leading to strong motor impairments. Vitamin A, through the action of its active metabolite retinoic acid (RA), is involved in the development, differentiation and protection of SNc dopaminergic neurons. However, the bioavailability of retinoic acid in the brain decreases with aging. Prior reports suggest that altered vitamin A signaling is implicated in the etiology of Parkinson’s disease, though the mechanisms are poorly understood. Here we hypothesize that nutritional supplementation with vitamin A may reduce dopaminergic cells loss by increasing RA levels in the brain, thus delaying the progression of the disease. We showed that rats deprived of vitamin A became progressively impaired in their motor functions and were unable to perform correctly the rotarod test after thirteen weeks of deprivation. However, locomotor functions were improved after just three weeks of vitamin A supplementation. To assess the effect of vitamin A supplementation, we modeled Parkinson’s disease in rat. Dopaminergic neurons were selectively deleted with unilateral injection of 6-hydroxydopamine (6-OHDA) toxin into rat’s striatum. Rats fed a vitamin A supplemented diet (20UI/g) for five weeks prior to the toxin injection exhibited an improvement in rotarod test compared to rats fed with control diet (5UI/g). Degeneration of dopaminergic terminals was assessed with stereological analysis of tyrosine hydroxylase staining in the striatum. Finally, dopamine levels in striatum were measured with HPLC. These preliminary data established the link between dietary vitamin A and dopaminergic system in PD. Future work will focus on establishing its underlying mechanisms and molecular basis.
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https://hal.inrae.fr/hal-02737346
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Submitted on : Tuesday, June 2, 2020 - 7:07:01 PM
Last modification on : Tuesday, September 7, 2021 - 2:52:06 PM

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  • HAL Id : hal-02737346, version 1
  • PRODINRA : 477818

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Anaïs Marie, Julien Leroy, Véronique Pallet, Sylvie Vancassel, Clémentine Bosch-Bouju. Implication of vitamin A in neuroprotection of dopaminergic neurons in a rat model of Parkinson's disease. 13. IBAGS Meeting, Apr 2019, Biaritz, France. 2019, Scientific Programme. ⟨hal-02737346⟩

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