TGF-beta 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; CRESPO ROSANA; HEREÑÚ CLAUDIA BEATRIZ

Congreso; XXXVIII Annual Meeting of the SAN 2023; 2023

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