TGF-β3 Gene Administration Mitigates Hippocampal Alterations in a Parkinson?s disease Model

Ciudad Autónoma de Buenos Aires

Congreso; SAN 2024 Annual Meeting; 2024

Sociedad Argentina de Neurociencias

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 GF-β trophic factor famil 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 ia an adeno iral ector (rAD-TGF-β3) in a Parkinson?s disease rat model induced b 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 therap ma be a promising treatment strateg for Parkinson?s disease for both its motor and non-motor symptoms.