Identification of differentially expressed genes induced in the rat brain by acetyl- l-carnitine as evidenced by suppression subtractive hybridisation

• Published in: Brain research. Molecular brain research. 2004-12, Vol.132 (1), p.57-63
• Main Authors: Traina, Giovanna, Valleggi, Simona, Bernardi, Rodolfo, Rizzo, Milena, Calvani, Menotti, Nicolai, Raffaella, Mosconi, Luigi, Durante, Mauro, Brunelli, Marcello
• Format: Article
• Language: English
• Subjects: 14-3-3 protein; 14-3-3 Proteins - biosynthesis; 14-3-3 Proteins - genetics; Acetyl- l-carnitine; Acetylcarnitine - metabolism; Acetylcarnitine - pharmacology; Animals; ATP synthase lipid-binding protein; Biological and medical sciences; Brain - drug effects; Brain - metabolism; Down-Regulation - drug effects; Down-Regulation - genetics; Energy Metabolism - drug effects; Energy Metabolism - genetics; Fundamental and applied biological sciences. Psychology; Gene Expression Profiling; Gene Expression Regulation - drug effects; Gene Expression Regulation - genetics; Gene Library; Heat shock protein; Heat-Shock Proteins - biosynthesis; Heat-Shock Proteins - genetics; Hirudo medicinalis; HSP72 Heat-Shock Proteins; Male; Mitochondrial Proton-Translocating ATPases - biosynthesis; Mitochondrial Proton-Translocating ATPases - genetics; Nerve Growth Factors - metabolism; Nerve Growth Factors - pharmacology; Nerve Tissue Proteins - biosynthesis; Nerve Tissue Proteins - genetics; Nucleic Acid Hybridization - methods; Rats; Rats, Wistar; RNA, Messenger - drug effects; RNA, Messenger - metabolism; Suppression subtractive hybridisation; Up-Regulation - drug effects; Up-Regulation - genetics; Vertebrates: nervous system and sense organs
• ISSN: 0169-328X; 1872-6941
• DOI: 10.1016/j.molbrainres.2004.09.006

Acetyl- l-carnitine (ALC) is a molecule widely present in the central nervous system (CNS) formed by the reversible acetylation of carnitine. It acts by stimulating energy metabolism. Reported neurobiological effects of this substance include modulation of brain energy and phospholipid metabolism; cellular macromolecules (including neurotrophic factors and neurohormones); synaptic transmission of multiple neurotransmitters. ALC is of considerable interest for its clinical application in Alzheimer's disease and in the treatment of painful neuropathies. There are experimental data that it affects attention and antagonizes deterioration of ability to learn, improving long-term memory. Moreover, ALC influences nonassociative learning of sensitization type in Hirudo medicinalis. These findings are suggesting that ALC might exert its effects by means of new protein synthesis. ALC or saline solution was injected intraperitoneally each day for 21 days in rats. Poly(A) + RNAs were isolated from control and treated rat brain. Suppression subtractive hybridisation (SSH) method was applied for the generation of subtracted cDNA libraries and the subsequent identification of differentially expressed transcripts after treatments. The technique generates an equalized representation of differentially expressed genes irrespective of their relative abundance, and it is based on the construction of forward and reverse cDNA libraries that allow the identification of the genes that are regulated or switched off/on after ALC treatment. We identified two modulated genes, the isoform γ of 14-3-3 protein and a precursor of ATP synthase lipid-binding protein, and one gene switched on by the treatment, the heat shock protein hsp72.