Investigation of the effect of vasoactive intestinal peptide (VIP) on alpha-synuclein accumulation in Striatum and Substantia nigra and neurogenesis in experimental Parkinson models

Aim : Our aim is to evaluate the potential effect of VIP, renowned for neuromodulatory, neurotrophic and neuroprotective effects, on alpha-synuclein accumulation and neurogenesis in 6-hydroxydopamine (6-OHDA) and rotenone experimental Parkinson model rats. Methods: For rotenone and 6-OHDA models, 36 Sprague-Dawley rats weighing 200-250 grams were used as control/sham, toxicated and toxicated VIP treated groups (n=6). 6-OHDA model was established by stereotaxic injection of 6-OHDA intrastriatally, rotenone model was achieved by 2.5 mg/kg/day injection of rotenone intraperitoneally for eight weeks. Both treatment groups received 25 ng/kg VIP every other day throughout eight weeks, other groups received an equal volume of saline intraperitoneally. Locomotor activity test was performed in eighth week. After sacrification, olfactory bulb, subventricular zone (SVZ), dentate gyrus, striatum and subtantia nigra sections were immunohistochemically stained. Section images were analysed using Image-J and data was compared statistically. Results: While VIP treatment exerted an increase comparable to controls in locomotor activity lowered by rotenone (p<0,05), caused no alterations in 6-OHDA model. No significant alteration in alpha-synuclein aggregation was observed in rotenone groups. In SVZ, while VİP showed no effect on nestin immunoreactivity elevation in toxicated groups (p<0,05), it increased doublecortin immunoreactivity in 6-OHDA model compared to sham and toxicated groups (p<0,05). VİP did not exert significant alterations in remaining parameters. Conclusion: Alterations in neurogenesis process was compared simultaneously in rotenone and 6-OHDA Parkinson models, in-vivo VIP treatment increased SVZ neuroblast area in 6-OHDA but not rotenone model, providing a differential effect of VIP in distinct models. Keywords: Parkinson's disease, 6-hydroxydopamine, rotenone, neurogenesis, alpha-synuclein, vasoactive intestinal peptide.