Global DNA methylation profiling of manganese-exposed human neuroblastoma SH-SY5Y cells reveals epigenetic alterations in Parkinson’s disease-associated genes

Manganese (Mn) is an essential trace element required for optimal functioning of cellular biochemical pathways in the central nervous system. Elevated exposure to Mn through environmental and occupational exposure can cause neurotoxic effects resulting in manganism, a condition with clinical symptoms identical to idiopathic Parkinson’s disease. Epigenetics is now recognized as a biological mechanism involved in the etiology of various diseases. Here, we investigated the role of DNA methylation alterations induced by chronic Mn (100 µM) exposure in human neuroblastoma (SH-SY5Y) cells in relevance to Parkinson’s disease. A combined analysis of DNA methylation and gene expression data for Parkinson’s disease-associated genes was carried out. Whole-genome bisulfite conversion and sequencing indicate epigenetic perturbation of key genes involved in biological processes associated with neuronal cell health. Integration of DNA methylation data with gene expression reveals epigenetic alterations to PINK1, PARK2 and TH genes that play critical roles in the onset of Parkinsonism. The present study suggests that Mn-induced alteration of DNA methylation of PINK1–PARK2 may influence mitochondrial function and promote Parkinsonism. Our findings provide a basis to further explore and validate the epigenetic basis of Mn-induced neurotoxicity

Manganese exposure: linking down-regulation of miRNA-7 and miRNA-433 with α-synuclein overexpression and risk of idiopathic Parkinson's disease

Manganese is an essential trace element however elevated environmental and occupational exposure to this element has been correlated with neurotoxicity symptoms clinically identical to idiopathic Parkinson's disease. In the present study we chronically exposed human neuroblastoma SH-SY5Y cells to manganese (100 μM) and carried out expression profiling of miRNAs known to modulate neuronal differentiation and neurodegeneration. The miRNA PCR array results reveal alterations in expression levels of miRNAs, which have previously been associated with the regulation of synaptic transmission and apoptosis. The expressions of miR-7 and miR-433 significantly reduced upon manganese exposure. By in silico homology analysis we identified SNCA and FGF-20as targets of miR-7 and miR-433. We demonstrate an inverse correlation in expression levels where reduction in these two miRNAs causes increases in SNCA and FGF-20. Transient transfection of SH-SY5Y cells with miR-7 and miR-433 mimics resulted in down regulation of SNCA and FGF-20 mRNA levels. Our study is the first to uncover the potential link between manganese exposure, altered miRNA expression and parkinsonism: manganese exposure causes overexpression of SNCA and FGF-20 by diminishing miR-7 and miR-433 levels. These miRNAs may be considered critical for protection from manganese induced neurotoxic mechanism and hence as potential therapeutic targets

Investigations on Fe-doped strontium barium niobate, single phase ferroelectric and magnetodielectric compounds

To understand possible interaction between magnetic and electric order parameters of Fe-doped SrxBa1-xNb2O6 (SBN), Fe-doped Sr0.5Ba0.5Nb2O6 (SBN50) and Sr0.4Ba0.6Nb2O6 (SBN40) are synthesized and investigated. Synthesis has been carried out via ceramic route. The paper reports synthesis, crystal structure, dielectric properties, P–E hysteresis loops, M–H hysteresis loops and magneto-capacitance of the Fe-doped SBN compositions. All the compositions are observed to exhibit a useful value of magneto-capacitance, especially at frequencies less than 10 kHz

Effect of Ni doping on ferroelectric, dielectric and magneto dielectric properties of strontium barium niobate ceramics

119-124To understand possible interactions between magnetic and electric order parameters of Ni doped SrxBa1-xNb2O6, Ni doped Sr0.5Ba0.5Nb2O6 (SBN50) and Sr0.4 Ba0.6 Nb2 O6 (SBN40) are synthesized and investigated. Synthesis has been carried out via ceramic route. The paper reports the synthesis, crystal structure, dielectric properties, PE hysteresis loops, M-H hysteresis loops and magneto-capacitance of the Ni doped SBN compositions. All the compositions are observed to exhibit a useful value of magneto-capacitance, especially at frequencies less than 10 kHz