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Medicina is published by MDPI from Volume 54 Issue 1 (2018). Articles in this Issue were published by another publisher in Open Access under a CC-BY (or CC-BY-NC-ND) licence. Articles are hosted by MDPI on as a courtesy and upon agreement with Lithuanian Medical Association, Lithuanian University of Health Sciences, and Vilnius University.
Open AccessArticle

Mildronate as a Regulator of Protein Expression in a Rat Model of Parkinson’s Disease

Department of Pathology, Faculty of Medicine, University of Latvia, Riga, Latvia
Department of Pharmacology, Faculty of Medicine, University of Latvia, Riga, Latvia
Latvian Institute of Organic Synthesis, Riga, Latvia
Author to whom correspondence should be addressed.
Medicina 2011, 47(10), 79;
Received: 29 September 2011 / Accepted: 31 October 2011 / Published: 5 November 2011
Background. Mildronate (3-[2,2,2-trimethylhydrazinium] propionate dihydrate) traditionally is a well-known cardioprotective drug. However, our recent studies convincingly demonstrated its neuroprotective properties. The aim of the present study was to evaluate the influence of mildronate on the expression of proteins that are involved in the differentiation and survival of the nigrostriatal dopaminergic neurons in the rat model of Parkinson’s disease (PD). The following biomarkers were used: heat shock protein 70 (Hsp70, a molecular chaperone), glial cell line-derived nerve growth factor (GDNF, a growth factor promoting neuronal differentiation, regeneration, and survival), and neural cell adhesion molecule (NCAM).
Material and Methods
. PD was modeled by 6-hydroxydopamine (6-OHDA) unilateral intrastriatal injection in rats. Mildronate was administered at doses of 10, 20, and 50 mg/kg for 2 weeks intraperitoneally before 6-OHDA injection. Rat brains were dissected on day 28 after discontinuation of mildronate injections. The expression of biomarkers was assessed immunohistochemically and by Western blot assay.
. 6-OHDA decreased the expression of Hsp70 and GDNF in the lesioned striatum and substantia nigra, whereas in mildronate-pretreated (20 and 50 mg/kg) rats, the expression of Hsp70 and GDNF was close to the control group values. NCAM expression also was decreased by 6-OHDA in the striatum and it was totally protected by mildronate at a dose of 50 mg/kg. In contrast, in the substantia nigra, 6-OHDA increased the expression of NCAM, while mildronate pretreatment (20 and 50 mg/kg) reversed the 6-OHDA-induced overexpression of NCAM close to the control values.
Conclusion. The obtained data showed that mildronate was capable to regulate the expression of proteins that play a role in the homeostasis of neuro-glial processes.
Keywords: mildronate; protein expression; neuroprotection mildronate; protein expression; neuroprotection
MDPI and ACS Style

Isajevs, S.; Isajeva, D.; Beitnere, U.; Jansone, B.; Kalvinsh, I.; Klusa, V. Mildronate as a Regulator of Protein Expression in a Rat Model of Parkinson’s Disease. Medicina 2011, 47, 79.

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