Creatine as a neuroprotective agent in manganese-induced neurotoxicity

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Shatha I. Farah (Creator)
Institution
The University of North Carolina at Greensboro (UNCG )
Web Site: http://library.uncg.edu/
Advisor
Keith Erikson

Abstract: Manganese (Mn) is a trace metal that is essential for optimal functioning of mammalian systems. However, excessive exposure to Mn is known to cause an extrapyramidal disease. Presently, Mn-induced neurotoxicity has no cure. In these studies, we examined the effectiveness of creatine therapy on models of Mn neurotoxicity. Primary astrocytes were cultured and divided into five groups: controls (CN), Mn group (300 μM MnCl2 for 24 hour), creatine group (1 mM creatine monohydrate for 24 hour), Mn followed by creatine treatment group (MnCr), and creatine treatment followed by Mn exposure group (CrMn). Results showed a significant increase in Mn concentrations in Mn and CrMn groups (p < 0.05), with Mn group showing a significant decrease in cellular viability and creatine attenuating the toxic effects of Mn in the MnCr and CrMn groups. A significant elevation in glutamate-aspartate transporter gene expression was seen in CrMn compared to CN, and glutathione peroxidase (GPx) gene expression was significantly decreased in MnCr and CrMn groups. Based on this study, we concluded that creatine may have some sort of neuroprotection in Mn-exposed primary cultured astrocytes. Following the astrocyte study, four brain regions from male Sprague-Dawley rats exposed to 1 g MnCl2 /L in water (Mn; n=6), given intraperitoneal injections of 75 g/kg body weight monohydrate creatine (Cr; n=6), or exposed to Mn and creatine injections (MnCr; n=6), or received no creatine injection with no exposure to Mn (CN; n=6) were dissected and processed. The effect of waterborne exposure to Mn and creatine treatment on gene expression profiles showed a statistical trend for an increase in glutamate-transporter-1 gene expression in MnCr group in the globus pallidus (GP) (p=0.066) and caudate-putamen (CP) (p=0.052) when compared to CN. A statistical trend for increased GPx gene expression was observed in Cr group of the substania nigra (SN) (p= 0.055) and MnCr group of cortex (CX) (p=0.051). Heme oxygenase-1 (HMX-1) in the Mn group of SN showed a statistical trend for increased gene expression (p= 0.072) when compared to CN, and GP showed a statistical trend towards an increased HMX-1 expression in Mn group (p = 0.08) when compared to MnCr group. Finally, brain cytosolic creatine kinase gene expression was significantly lowered in the MnCr group of SN when compared to CN. Our study suggests that subchronic waterborne exposure to Mn does not cause significant changes on markers of oxidative stress and creatine treatment exerts some neuroprotection overall.

Additional Information

Publication
Thesis
Language: English
Date: 2011
Keywords
Creatine, Manganese, Neuroprotection, Neuroprotective, Neurotoxicity, Parkinson
Subjects
Creatine $x Therapeutic use $x Effectiveness
Manganese $x Toxicology