Disorders of the Nervous System
Author: Matías Jávega Cometto | Email: matias.javega@unc.edu.ar
Matías Jávega Cometto1°, Leandro Gabriel Champarini1°,Aracely Janneth Naranjo Viteri1°, Rosana Crespo1°, Claudia Beatriz Hereñú1°
1° Instituto de Farmacología Experimental de Córdoba (IFEC-CONICET), Departamento de Farmacología Otto Orsingher, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina
Non-motor symptoms in Parkinson’s disease (PD), such as anxiety disorders and cognitive impairments, significantly impact patients’ quality of life and often appear before motor symptoms. These observations suggest that brain regions involved in cognitive functions, like the hippocampus, are affected along with the classic dopaminergic nigrostriatal pathway. Treatments should therefore target not just neuronal loss but also processes that contribute to damage in these regions like inflammation and oxidative stress. TGF-β3, a member of the TGF-β trophic factor family known for its anti-inflammatory properties and role in dopaminergic neuron differentiation, shows promise as a therapeutic approach. This study assessed the effect of intracisternal administration of the TGF-β3 gene via an adenoviral vector (rAD-TGF-β3) in a Parkinson’s disease rat model induced by 6-hydroxydopamine (6-OHDA). Results demonstrated that 6-OHDA impaired cognitive and anxiety-like behaviors before mild motor disabilities appeared, accompanied by increased inflammation in the hippocampus and reduced dopaminergic markers in the striatum. rAD-TGF-β3 administration mitigated these behavioral alterations, decreased hippocampal inflammation, and eventually restored dopaminergic markers in the striatum at a later time. These results suggest that TGF-β3 gene therapy may be a promising treatment strategy for Parkinson’s disease for both its motor and non-motor symptoms.