Untangling the Role of Metallothionein- III in Cadmium Induced Alteration in Brain Biogenic Amines: Protective Potential of Quercetin

Cadmium, a non-transition heavy metal, is largely responsible for the development of neurological and neurodegenerative disorders. Epidemiological and prevalence studies suggest that high exposure to cadmium and consecutive high cumulation in the human body pose a high risk of various diseases. It has been identified that cadmium-induced motor deficits in rats are due to alterations in canonical and noncanonical Cyclic Adenosine (cAMP)-dependent PKA/DARRP32/PP1α associated with decreased Deficiency of Adenosine Deaminase 2 (DA-D2) receptors in the corpus striatum. Continuing those studies, current studies have been executed to untangle the role of Metallothionein- III in cadmium-induced alterations in biogenic amines in selected brain regions of rats. Treatment of rats with cadmium (5mg/kg, per oral) for 28 days caused a marked decrease in neurotransmitter levels in various brain regions while there was no significant change in DA turnover as compared to controls. Further, there was a striking increase in the levels of Metallothionein (MT-III) and levels of cadmium in these brain regions. Insilico studies involving ADMET Regression analysis further confirmed the changes wherein it has been shown that the cadmium easily crosses the blood-brain barrier and accumulates in the brain regions, binds with the Metallothionein and produces neurotoxicity. Interestingly, simultaneous exposure with quercetin (25mg/kg, per oral) was found to protect cadmium-induced alterations. The results exhibit that cadmium-induced alteration in biogenic amines may be associated with increased levels of metallothionein in the brain, predicting the toxicity of cadmium.