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Published on: January 7, 2014
Mildronate as a regulator of protein expression in a rat model of Parkinson's disease
Sergejs Isajevs1, Darja Isajeva, Ulrika Beitnere
1Department of Pathology, University of Latvia, Riga. Latvia. sergisajevs@inbox.lv
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.
Results:
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.
Insights
Mildronate demonstrates neuroprotective effects in a rat model of Parkinson's disease by regulating key proteins involved in neuronal survival and differentiation. This study highlights mildronate's potential in managing neurodegenerative conditions.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Mildronate, traditionally a cardioprotective agent, exhibits neuroprotective properties.
- Parkinson's disease (PD) is characterized by the degeneration of nigrostriatal dopaminergic neurons.
- Key proteins like Hsp70, GDNF, and NCAM are crucial for neuronal survival and differentiation.
Purpose of the Study:
- To investigate the effect of mildronate on the expression of Hsp70, GDNF, and NCAM in a rat model of PD.
- To evaluate mildronate's neuroprotective potential against 6-hydroxydopamine (6-OHDA)-induced neurodegeneration.
Main Methods:
- Parkinson's disease was modeled using unilateral intrastriatal 6-OHDA injections in rats.
- Mildronate was administered intraperitoneally at varying doses (10, 20, 50 mg/kg) for two weeks prior to 6-OHDA injection.
- Biomarker expression (Hsp70, GDNF, NCAM) was assessed using immunohistochemistry and Western blot.
Main Results:
- 6-OHDA reduced Hsp70 and GDNF expression, which was restored by mildronate (20 and 50 mg/kg).
- Mildronate (50 mg/kg) completely protected against 6-OHDA-induced decrease in striatal NCAM expression.
- Mildronate reversed 6-OHDA-induced overexpression of NCAM in the substantia nigra.
Conclusions:
- Mildronate effectively regulates proteins involved in neuro-glial homeostasis.
- The findings suggest mildronate possesses significant neuroprotective capabilities in the context of Parkinson's disease.
- Mildronate's ability to modulate key neuronal survival and differentiation markers warrants further investigation for PD treatment.
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