The effect of short-term administration of (-)-deprenyl and isatin on the expressions of some genes in the mouse brain cortex
Valerii Fedchenko, Alexander Globa, Alexei Kaloshin, Inga Kapitsa, Lubov Nerobkova, Elena Val’dman, Olga Buneeva, Vivette Glover, Alexei Medvedev
Med Sci Monit 2008; 14(12): BR269-273
Isatin (indoledione 2,3) is an endogenous indole found in the mammalian brain, peripheral tissues, and body fluids. It exhibits many neurophysiological and neuropharmacological effects. It shares some common molecular targets with (-)-deprenyl, a neuroprotective pharmacological drug. Some isatin effects imply a possible influence of gene expression; however, no isatin-responsive genes have yet been identified.
Material and Method: In this study the effects of a three-week administration of isatin (20 mg/kg) or (-)-deprenyl (1 mg/kg) on the expressions of several putative isatin/deprenyl-responsive genes in the mouse cortex were compared using real-time PCR.
Results: Both treatments caused similarly significant decreases in superoxide dismutase (SOD) mRNA. Treatment of mice with either drug decreased glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA, although only in the deprenyl-treated mice was this significant (p<0.01). No significant changes were found in cortex mRNA content of monoamine oxidase A or monoamine oxidase B.
Conclusions: The results suggest that isatin and (-)-deprenyl have some common target genes and this supports the idea that isatin may be an endogenous partial functional agonist of (-)-deprenyl. Since GAPDH mRNA expression is sensitive to the pharmacological treatments, these results also question the applicability of GAPDH as a reference gene in gene expression studies.
Keywords: Selegiline - pharmacology, Polymerase Chain Reaction, Monoamine Oxidase Inhibitors - pharmacology, Mice, Mice, Inbred C57BL, Male, Isatin - pharmacology, Glyceraldehyde-3-Phosphate Dehydrogenases - metabolism, Superoxide Dismutase - metabolism, Gene Expression Regulation - drug effects, Cerebral Cortex - metabolism, Animals