Altered striatal dopamine release following a sub-acute exposure to manganese

• Published in: Journal of neuroscience methods Vol. 202; no. 2; pp. 182 - 191
• Main Authors: Khalid, Madiha, Aoun, Rabab A., Mathews, Tiffany A.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.11.2011
• Subjects: Animals; Caudate–putamen; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Corpus Striatum - physiopathology; Disease Models, Animal; Dopamine - analysis; Dopamine - deficiency; Dopamine - secretion; Dopamine D2 receptors; Dopamine transporter; Male; Manganese - analysis; Manganese - toxicity; Manganese Poisoning - metabolism; Manganese Poisoning - physiopathology; Mice; Mice, Inbred C57BL; Microdialysis; Parkinsonian Disorders - chemically induced; Parkinsonian Disorders - metabolism; Parkinsonian Disorders - physiopathology; Voltammetry; Voltammetry; Caudate–putamen; Dopamine transporter; Mice; Microdialysis; Dopamine D2 receptors
• ISSN: 0165-0270; 1872-678X
• DOI: 10.1016/j.jneumeth.2011.06.019

► Tissue content, microdialysis, and FSCV used to study sub-acute Mn treated mice. ► Sub-acute Mn treatment to mice over 7 days; neurochemical analysis over 21 days. ► Tissue content confirmed the accumulation of striatal Mn 21 days past final treatment. ► Microdialysis elucidated attenuation in basal and potassium stimulated DA levels. ► FSCV shows lowered release with no difference in DA transporter or D2 receptors. Certain metals that are necessary for regulating biological function at trace levels hold the potential to become neurotoxic when in excess. Specifically, chronic exposure to high levels of manganese leads to manganism, a neurological disorder that exhibits both motor and learning deficits similar to Parkinson's disease. Since Parkinson's disease symptomatology is primarily attributed to dopamine neurodegeneration in the striatum, dopamine system dysfunction has been implicated in the onset of manganism. In this study, dopamine system function in the dorsal striatum was evaluated in C57Bl/6 mice, 1, 7, and 21 days following repeated injections of manganese(II) chloride (50 mg/kg, subcutaneous) intermittently for 7 days. Tissue content analysis confirmed the presence of persistent accumulation of manganese in the striatum up to 21 days after cessation of treatment. In vitro fast scan cyclic voltammetry examined the effect of sub-acute manganese on electrically stimulated dopamine release and uptake in the striatum. While no difference was observed in uptake rates following manganese treatment, dopamine release was attenuated on days 7 and 21, compared to control levels. Basal levels of extracellular dopamine determined by the zero net flux microdialysis method were significantly lower in manganese-treated mice at 7 days post-treatment. On the other hand, potassium stimulated increases in extracellular dopamine were attenuated at all three time points. Together, these findings indicate that repeated manganese exposure has long-term effects on the regulation of exocytotic dopamine release in the striatum, which may be involved in the mechanism underlying manganese toxicity.