TGF-β3 Overexpression Mitigates Cognitive Impairments and Neuroinflammation in a Rat Model of Early Parkinson?s Disease

Congreso; XL SAN Meeting; 2025

Parkinson ́ s disease is a complex pathology marked neurodegeneration in dopaminergic neurons of the nigrostriatal system. The early prodromal phase has been recognized for the presence of nonmotor symptoms that could be predictive of later motor disease. By inducing dopaminergic neuron death with 6-hydroxydopamine (6-OHDA) in male Wistar rats we have observed alterations in cognitive functions within 3 weeks of the surgery. We aimed to test the potential of TGF-β3, a trophic and anti-inflammatory factor, to mitigate these early changes. We administered an adenoviral vector containing the TGF-β3 gene (RAd-TGF-β3), or its control, 14 days after 6-OHDA (or vehicle) surgery. On day 21 we performed the Barnes Maze test, the Novel Object Recognition test and the Modified Y-Maze. We found that RAd-TGF-β3 in animals with 6-OHDA induced a better performance in these tests compared to animals administered with the control vector. At this time we demonstrated an antiinflammatory effect measuring pro-inflammatory factors? expression (IL-1, IL-6, TNF-α) in the hippocampus, as well as glial activation markers (CYP46, IGF-1), observing a reduction with RAdTGF-β3 in comparison to 6-OHDA animals. Moreover, latency values in Barnes Maze correlate more with expression values of TNF-α than with other cytokines. We conclude that the overexpression of TGF-β3 can overcome the damaging processes induced by 6-OHDA and therefore has potential to treat parkinsonism?s early impairments.