Long-term expression of a synthetic gene encoding the antiinflammatory peptide thymulin.

MOREL GR, BROWN OA, SOSA YE, HEREÑU CB,ZUCCOLILLI GO, PORTIANSKY EL, DAEDENNE M, GOYA RG

Huerta Grande, Cordoba

Taller; VIII Taller Argentino de Neurociencias; 2006

Internacional Brain Researche Organization (IBRO).

Thymulin is a thymic peptide with antiinflammatory activity in the brain. We constructed a recombinant adenoviral vector, RAd-FTS, expressing a synthetic DNA sequence encoding met-FTS, a biologically active analog of thymulin and used it to implement central gene transfer in rats. Thymulin content in  brain tissue was determined by bioassay. Reporter gene expression in the susbstantia nigra (SN) and medial basal hypothalamus (MBH) was quantitated by enzymohistochemistry or fluorescence microscopy using an appropriate image analysis software. Stereotaxic brain injection of RAd-FTS induced steady expression levels of met-FTS for at least 90  days, whereas expression of adenovirally-transferred reporter genes coding for green fluorescent protein fused to HSV thymidine kinase (GFP-TK)fus or E. coli beta-galactosidase (beta-gal), declined rapidly and was no longer detectable at post-injection day 14 and 60, respectively. We conclude that RAd-FTS constitutes a suitable biotechnological tool for the assessment of neuroprotective thymulin gene therapy in animal models of nigral and hypothalamic dopaminergic neurodegeneration induced by pro-inflammatory agents.