TITLE:
Synthetic Peptides Affect the Expression of Gdnf and Gdnf Receptors in Rats with 6-OHDA-Induced PD-Like Parkinsonism
AUTHORS:
Elena V. Filatova, Maria I. Shadrina, Timur A. Kolomin, Ludmila A. Andreeva, Nikolay F. Myasoedov, Petr A. Slominsky
KEYWORDS:
6-OHDA, Parkinson’s Disease, Semax, DNSP-5, Gene Expression
JOURNAL NAME:
World Journal of Neuroscience,
Vol.6 No.4,
October
19,
2016
ABSTRACT: Parkinson’s
disease (PD) is the second most common severe neurodegenerative disorder. It is
characterized by progressive degeneration of dopaminergic neurons in the
substantia nigra pars compacta. Unfortunately, PD remains incurable. Therapy
based on regulatory peptides, particularly neuroprotective peptides, which can
sustain or activate neuron plasticity to enable their survival and function in
difficult environments and after violated homeostasis, is a promising approach
to cure PD. Some studies show that the synthetic analogs of natural peptides
may be used as an etiological or at least a complementary therapy in PD.
Therefore, in the present pilot study, we investigated the effects of the
synthetic peptides Semax and dopamine neuron stimulating peptide (DNSP-5), and
a new synthetic Semax-DNSP-5 hybrid peptide (SD) on the functioning of brain
neurons. An analysis of the levels of dopamine (DA), noradrenaline (NA),
5-hydroxytriptamine (5-HT), an expression analysis of Gdnf and Gdnf receptor genes Gfra1, Gfra2, Gfra3, Gfra4, and Gfral in various regions of the brain of
rats with 6-OHDA-induced PD-like parkinsonism, and a study of the motor
activity of the rats in an “open field” test showed that DNSP-5 and SD elevated
the level of DA in the nonlesioned striatum. DNSP-5 also increased the
expression of Gfra1 and Gfra2 in the nonlesioned striatum and
lesioned substantia nigra (SN) which suggested that DNSP-5 had compensatory and neuroprotective properties. SD
demonstrated similar, albeit less pronounced effects to DNSP-5 on DA metabolism
and gene expression. Of the peptides studied, only SD tended to increase the
horizontal and vertical activity of rats. In conclusion, these findings suggest
that DNSP-5 and SD have potential neuroprotective properties and may stimulate
the surviving DA neurons.