Molecular Markers of Endogenous Neuroprotection in the Brain of Rats With Experimental Parkinson's Disease and on the Background of Using New Pharmacotherapy Schemes

Abstract

Parkinson's disease (PD) is one of the most common neurodegenerative diseases in the elderly.
 The aim of the study. To study apoptotic processes and their role in the formation of dopaminergic neurodegeneration and to develop new treatment regimens with a specific neuroprotective effect on the dopaminergic system.
 Materials and methods. The study was carried out on 90 Wistar rats at the age of 6 months weighing 220–290 grams. Parkinsonism was induced by the administration of the neurotoxin MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) to experimental rats with neuroprotective treatment: I – Intact (passive control); II – animals with experimental Parkinson's disease (PD, active control); III – PD + Amantadine (AM) IV – PD + AM + Cerebrocurin; V – PD + AM + Pramistar; VI – PD + AM + Gliatilin; VII – PD + AM + Noofen; VIII – PD + AM + Pronoran; IX – PD + AM + Melatonin.
 Results. The obtained data 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, HSP70 genes, bcl-2 proteins and decrease c-fos proteins with caspase-3 as markers of apoptosis and can also serve as a molecular marker for the activation of endogenous neuroprotection mechanisms under the conditions of an experimental PD.
 Conclusions. The study 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 the treatment of PD.