cDNA Array Analysis of Gene Expression Profiles in Brain of Mice Exposed to Manganese

Abstract

This study is performed to detect changes of gene expression in substantia nigra (SN) and striatum in manganese (Mn)-exposed mice brain. The cDNA array is a recently developed molecular biological method that can detect the differential expression of several hundreds of genes simultaneously and is therefore advantageous in the study of trace metal intoxication effect at the genetic level. Using this technology, we discovered 5 genes in the mouse striatum and 9 genes in SN changed by more than 50% following Mn exposure. Depression were observed in two genes (neural cell adhesion protein BIG2, heavy neurofilament subunit genes) in striatum and three genes (light neurofilament subunit, brain acyl-CoA synthetase II, heavy neurofilament subunit genes) in the SN. However three genes (N-acetylglucosaminyltransferase I, S100β β β β β, and synaptonemal complex protein I genes) in striatum and six genes (noggin, striatin, Ost oncogene, S100β β β β β, calcium/calmodulindependent protein kinase kinase beta, and N-acetylglucosaminyltransferase I genes) in SN were elevated following Mn exposure. Immunohistochemical study revealed that protein levels of S100β β β β β also increased following Mn treatment. Activated astrocytes overexpressing S100β β β β β are invariably and intimately associated with decreased expression of heavy and light neurofilament subunits which is a distinguishing feature of neurodegeneration by Mn exposure. All our findings suggested that neuronal degenerations occur in SN as well as striatum of mice exposed to Mn.

Assessment of dry season surface, ground, and treated water quality in the Cape Coast municipality of Ghana

“…However, excessive Mn is also toxic to the brain and can produce an irreversible syndrome resembling Parkinson's disease (Donaldson 1987;Baek et al 2003Baek et al , 2004Olanow 2006). This neurologic syndrome, known as "manganism" (Latchoumycandane et al 2005;Wasserman et al 2006) is thus characterized by a Parkinson-like condition with weakness, anorexia, apathy, slowed speech, emotionless facial expression, and slow movement of the limbs.…”

“…Mn is an essential element for metalloproteins, such as glutamate synthetase, mitochondrial superoxide dismutase (Prohaska 1987;Baek et al 2004). However, excessive Mn is also toxic to the brain and can produce an irreversible syndrome resembling Parkinson's disease (Donaldson 1987;Baek et al 2003Baek et al , 2004Olanow 2006).…”

Manganese and its Role in Parkinson’s Disease: From Transport to Neuropathology

“…In a genome-wide study on cultured human astrocytes (Sengupta et al 2007), Mn-induced expression changes were noted in genes involved in inflammation (upregulated), DNA replication, and repair (downregulated). Gene expression on Mn-treated mice brains (Baek et al 2004) mainly showed an upregulation of the S100β gene, and the increase of the protein was confirmed by immunohistochemistry. Instead, neurofilament subunit genes were downregulated in the striatum and in the substantia nigra.…”

“…The few studies available have addressed gene expression changes in Mn-treated cells of human (Sengupta et al 2007) or rodent origin (Baek et al 2004;HaMai et al 2006). In a genome-wide study on cultured human astrocytes (Sengupta et al 2007), Mn-induced expression changes were noted in genes involved in inflammation (upregulated), DNA replication, and repair (downregulated).…”

A Pilot Study of Gene Expression Analysis in Workers with Hand-Arm Vibration Syndrome

“…A particular study which assessed in vitro cytogenetic effects of exposure to lowvibration regimes failed to detect an increase in SCE frequency in peripheral blood lymphocytes [4][5][6] . Occupational exposure to whole-body vibration and low frequency noise may have genotoxic effects in humans expressed as an increase in sister chromatid exchange levels in lymphocytes.…”