Trace Elements in Medicine (Moscow)
2018, 19(4): 16-19
ORIGINAL PAPERS

INTRANASAL EXPOSURE TO MANGANESE INDUCES ACTIVATION OF CALPAINS IN RAT STRIATUM

I. Ivleva¹, N. Pestereva¹, Z. Muruzheva¹, M. Tikhomirova², M. Karpenko^1,3

¹ Department of Physiology (Pavlov's), Institute of Experimental Medicine, Akademika Pavlova Street, 12, St. Petersburg, Russia
² Institute of Molecular Life Sciences, University of Zurich, Winterthurer strasse 190CH-8057, Zurich, Switzerland
³ Department of Biophysics, PHNT, Peter the Great St. Petersburg Polytechnic University, 29 Polytechnicheskaya St., St. Petersburg, Russia

DOI: 10.19112/2413-6174-2018-19-4-16-19 

ABSTRACT. Manganese (Mn) is an essential trace element. However, at abnormally high intake levels, Mn starts to predominantly accumulate in the brain and cause neurotoxicity. Chronic exposure to excessive Mn levels can lead to a variety of Parkinson-like psychiatric and motor disturbances, termed manganism. Brain regions primarily affected by Mn are the basal ganglia, which is again similar to Parkinson disease. Treatment of manganism with levodopa and EDTA did not lead to a significant beneficial effect. For this reason, a search for new targets and pharmacological agents for treatment of Mn intoxication has become necessary. Another well described feature of Parkinson disease is a hyperactivation of a calpain system. Calpains are intracellular Ca2+-dependent cysteine proteases. Uncontrolled activation of calpains leads to neuronal death especially in dopaminergic neurons. Here, we provide an evidence to support the involvement of the calcium-dependent proteases, calpains, in the pathogenesis of manganism in a rat model. The participation of calpain-1 and calpain-2 was monitored in the striatum. Mn induced an increase of the activity of calpain-2 in the striatum, where the activity of calpain-1 was also increased but not its mRNA. We have also shown that Mn directly activates calpain-1 like calcium but not calpain-2 in vitro. We propose that calpains can be potential therapeutic targets for manganism.

KEYWORDS: manganese, manganism, neurodegeneration, calpains.