Disorders of the Nervous System
Author: Matías Jávega Cometto | Email: firstname.lastname@example.org
Matías Jávega Cometto 1°, Leandro Gabriel Champarini 1°, Aracely Janneth Naranjo Viteri 1°, Rosana Crespo 1°, Claudia Beatriz Hereñú 1°
1° Instituto de Farmacología Experimental de Córdoba (IFEC-CONICET), Departamento de Farmacología Otto Orsingher, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina
Parkinson’s disease is a neurodegenerative disorder associated with neuroinflammation and characterized by the progressive loss of nigro-striatal dopaminergic neurons. Our study focuses on the striatum area (CPu), where these neurons establish their synapses, and on non-motor symptoms that usually precede the motor deficits that occur in late stages of the disease. We have shown that 3 weeks after bilateral intrastriatal administration of selective neurotoxin 6-hydroxydopamine (6-OHDA) in Wistar male rats, the animals showed cognitive deficits and anxiety-like behavior that preceded motor disabilities. TGF-β3 is a cytokine that regulates cell proliferation, neurite outgrowth, and anti-inflammatory effects in the central nervous system. We aimed to generate overexpression of TGF-β3 with therapeutic goals in neuronal and glial cells. The introduction of the rat TGF-β3 coding sequence carried in a recombinant adenoviral vector (rAD-TGFβ3) into the cerebrospinal fluid 14 days after 6-OHDA administration, reduced cognitive impairment and anxiety-like behavior evaluated through behavioral tests. Through qRT-PCR and Western blot analysis of CPu samples we studied the expression of inflammatory cytokines and the content of presynaptic proteins. We conclude that rAD-TGFβ3 could be a possible therapeutic approach to restore and modulate the mentioned changes in the 6-OHDA Parkinson animal model.