Molecular markers of endogenous neuroprotection in the brain of rats with experimental Parkinson's disease treated with various pharmacotherapy regimens.

OBJECTIVE

Aim: To study apoptotic processes and their role in the formation of premature dopaminergic neurodegeneration, to identify key biomarkers for early diagnosis and implementation of complex measures towards braking the progression of PD in the early stages, to develop possible treatment regimens with a specific neuroprotective effect on the dopaminergic system.

PATIENTS AND

METHODS

Materials and

Methods

The experiment involved 90 Wistar rats (6 months old, 220-290 g). Parkinsonism was induced by the neurotoxin MPTP (N-methyl4-phenyl-1,2,3,6-tetrahydropyridine). Intact animals received saline (1 ml/100 g, i.p.); the control group received MPTP followed by saline. Rats were divided into nine groups: I - intact; II - PD control; III - PD + Amantadine (AM); IV - PD + AM + Cerebrocurin; V - PD + AM + Pramistar; VI - PD + AM + Gliatilin; VII - PD + AM + Noophen; VIII - PD + AM + Pronoran; IX - PD + AM + Melatonin.

RESULTS

Results

The data obtained indicate that neuroprotective therapy of PD with drugs such as melatonin, cerebrocurin, pronoran, and gliatilin in combination with amantadine leads to an increase in the expression of the HIF-1α, HIF-3α, and HSP70 genes, and can also serve as a molecular marker for the activation of endogenous neuroprotection mechanisms under experimental PD conditions.

CONCLUSION

Conclusions

We have experimentally demonstrated a new target of neuroprotection in PD conditions - apoptosis of dopamine-producing neurons and substantiated modulators of this process - drugs for combined therapy with amantadine (melatonin, cerebrocurin, pronoran, and gliatilin) as promising drugs for PD treatment.