Gene expression is modulated by acetyl-l-carnitine treatment in the rat brain

Acetyl-l-carnitine (ALC) has been shown to exhibit many neuromodulatory and neurotrophic actions on neuron activity. ALC is also a potential source of acetyl groups for the synthesis of acetylcholine in the mammalian brain. Several investigations reported that ALC treatment produces long lasting effects in learning processes, suggesting an involvement of gene modulation. The ALC action on gene expression is recently revealed by suppression subtractive hybridisation method (SSH) studies. SSH method was applied for the generation of subtracted cDNA libraries and the subsequent identification of differentially expressed transcripts after treatment of rats with ALC. 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 after ALC treatment. In recent experiments we have singled out an up-modulation of either 14,3,3 protein or of heat shock protein, contributing to establish a cytoprotective state in inflammation, neurodegenerative disorders, and aging. In addition, we showed that treatment produces a down-regulation on ATP-synthase lipid-binding protein gene expression. This effect has implications in ceroid lipofuscinosis pathology (Traina et al., Mol. Brain Res, 132, 57-63, 2004). More recently, we have observed that ALC treatment positively increases lisosomial H+-ATPase, also involved in lipofuscinosis, and VDAC1 gene expression. VDAC might exert an antiapoptotic role, and, seems to have a pivotal role on synaptic plasticity. In addition, ALC down-regulates ferritin-H expression. This gene seems involved in cell growth and differentiation. Our data on gene expression, therefore, might be of relevant importance for a human treatment of many clinical malignancies.