Developmental methylmercury toxicity in a 6- hydroxydopamine Parkinsonian rat model: evaluating Searsia chirindensis as a potential neuroprotectant.
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Date
2017
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Abstract
Methylmercury (MeHg) pollution in South Africa has escalated due to increased demand from industrial
sources such as coal-fired power stations. This had led to a growing interest in the effects of this metal
toxin on human health. Prenatal MeHg exposure has been suggested to be a silent neurotoxicant, which
may display its effects when triggered by a further neurotoxic insult. MeHg exposure during the perinatal
period leads to neurodevelopmental deficits resulting in motor and cognitive dysfunction. This suggests
that developmental MeHg exposure may predispose to the development of neurodegenerative diseases
such as Parkinson’s disease (PD). In this study, we investigate the effects of prenatal MeHg exposure at
adolescence and furthermore when subjected to an additional neurotoxic insult in a parkinsonian rat
model. Behavioural tests were conducted to assess motor deficits with neurochemical assessment of trace
element levels, total antioxidant capacity, dopamine and cytokine concentrations as well as gene
expression profiling. We also investigated a novel plant extract Searsia chirindensis (SC) as a potential
neuroprotectant by alleviating neurotoxicity. Overall the results of our study show that prenatal MeHg
exposure disrupts trace element homeostasis at adolescence asymptomatically however, these imbalances
are exaggerated following a further neurotoxic insult leading to motor deficits. Treatment with SC
reduced motor deficits in MeHg-exposed offspring as reflected by higher dopamine levels. Contrastingly,
treatment in the absence of MeHg exacerbated motor deficits with higher copper levels and upregulation
of antioxidant genes fth1 and nqo1 in response to the neurotoxic effect. Therefore the overall total
antioxidant capacity was not affected by SC. We also investigated the effect of SC on normal body
parameters to assess for toxicity. Our findings showed that SC did not affect either liver or renal function
and therefore does not affect the homeostasis of other body systems. Therefore conclusively our study
showed that developmental MeHg exposure results in altered trace element homeostasis which may
predispose to the development of neurodegenerative diseases such as Parkinson’s. We also showed that
SC stem-bark extract reduced motor deficits caused by 6-hydroxydopamine in MeHg-exposed offspring
but exacerbated neurotoxicity in its absence. SC also did not have any adverse effect on the homeostasis
of other body systems. Overall, this suggests that SC has potential as a neuroprotectant however further
studies must be conducted to fully elucidate the mechanisms involved in its effect.
Description
Doctoral Degree. University of KwaZulu-Natal, Durban.