RGD Reference Report - Mildronate as a regulator of protein expression in a rat model of Parkinson's disease. - Rat Genome Database

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Mildronate as a regulator of protein expression in a rat model of Parkinson's disease.

Authors: Isajevs, S  Isajeva, D  Beitnere, U  Jansone, B  Kalvinsh, I  Klusa, V 
Citation: Isajevs S, etal., Medicina (Kaunas). 2011;47(10):552-9.
RGD ID: 5686884
Pubmed: PMID:22186119   (View Abstract at PubMed)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Parkinson's disease  ISOHspa4 (Rattus norvegicus)5686884; 5686884protein:decreased expression:striatum (rat)RGD 
Parkinson's disease  IEP 5686884protein:decreased expression:striatum (rat)RGD 
Parkinsonism  ISOGdnf (Rattus norvegicus)5686884; 5686884protein:decreased expression:brainRGD 
Parkinsonism  IEP 5686884protein:decreased expression:brainRGD 

Objects Annotated

Genes (Rattus norvegicus)
Gdnf  (glial cell derived neurotrophic factor)
Hspa4  (heat shock protein family A (Hsp70) member 4)

Genes (Mus musculus)
Gdnf  (glial cell line derived neurotrophic factor)
Hspa4  (heat shock protein 4)

Genes (Homo sapiens)
GDNF  (glial cell derived neurotrophic factor)
HSPA4  (heat shock protein family A (Hsp70) member 4)


Additional Information