TGF-β Gene Therapy Attenuates Behavioral Impairments and Manifestations of Dopaminergic Neurodegeneration induced by 6-hydroxydopamine in rats

JÁVEGA COMETTO, MATÍAS; CHAMPARINI, LEANDRO GABRIEL; NARANJO VITERI, ARACELY JANNETH; HEREÑÚ, CLAUDIA BEATRIZ

San Luis

Congreso; SAN 2023 Annual Meeting; 2023

Sociedad Argentina de Neurociencias

Parkinson’s disease is a neurodegenerative disorder associated with neuroinflammationand characterized by the progressive loss of nigro-striatal dopaminergic neurons. Ourstudy 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 latestages of the disease. We have shown that 3 weeks after bilateral intrastriataladministration of selective neurotoxin 6-hydroxydopamine (6-OHDA) in Wistar male rats,the animals showed cognitive deficits and anxiety-like behavior that preceded motordisabilities. TGF-β3 is a cytokine that regulates cell proliferation, neurite outgrowth, andanti-inflammatory effects in the central nervous system. We aimed to generateoverexpression of TGF-β3 with therapeutic goals in neuronal and glial cells. Theintroduction of the rat TGF-β3 coding sequence carried in a recombinant adenoviralvector (rAD-TGFβ3) into the cerebrospinal fluid 14 days after 6-OHDA administration,reduced cognitive impairment and anxiety-like behavior evaluated through behavioraltests. Through qRT-PCR and Western blot analysis of CPu samples we studied theexpression of inflammatory cytokines and the content of presynaptic proteins. Weconclude that rAD-TGFβ3 could be a possible therapeutic approach to restore andmodulate the mentioned changes in the 6-OHDA Parkinson animal model.