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01 December 2008

The effect of short-term administration of (-)-deprenyl and isatin on the expressions of some genes in the mouse brain cortex

Valerii FedchenkoABD, Alexander GlobaBC, Alexei KaloshinB, Inga KapitsaB, Lubov NerobkovaB, Elena Val’dmanAB, Olga BuneevaBCDE, Vivette GloverADFG, Alexei MedvedevACDEFG

Med Sci Monit 2008; 14(12): BR269-273 :: ID: 869474

Abstract

Background
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, Isatin - pharmacology, Glyceraldehyde-3-Phosphate Dehydrogenases - metabolism, Superoxide Dismutase - metabolism, Gene Expression Regulation - drug effects, Cerebral Cortex - metabolism

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750