Gene and protein expression profiling of the fat-1 mouse brain

• Published in: Prostaglandins, leukotrienes and essential fatty acids leukotrienes and essential fatty acids, 2009, Vol.80 (1), p.33-42
• Main Authors: Ménesi, Dalma, Kitajka, Klára, Molnár, Eszter, Kis, Zoltán, Belleger, Jérome, Narce, Michael, Kang, Jing X, Puskás, László G, Das, Undurti N
• Format: Article
• Language: English
• Subjects: Adult and adolescent clinical studies; Advanced Basic Science; Alzheimer's disease; Animals; Biological and medical sciences; Brain - anatomy & histology; Brain - metabolism; Caenorhabditis elegans - genetics; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Endocrinology & Metabolism; Fat-1; Fatty Acid Desaturases - genetics; Fatty Acid Desaturases - metabolism; Fatty Acids, Unsaturated - chemistry; Fatty Acids, Unsaturated - metabolism; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Profiling; Gene Expression Regulation; Inflammation; Male; Medical sciences; Mice; Mice, Transgenic; Neurology; Neuronal dysfunction; Oligonucleotide Array Sequence Analysis; Organic mental disorders. Neuropsychology; Polyunsaturated fatty acids; Protein Array Analysis; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Vertebrates: endocrinology
• ISSN: 0952-3278; 1532-2823
• DOI: 10.1016/j.plefa.2008.11.006

Abstract Polyunsaturated fatty acids (PUFAs) are essential structural components of all cell membranes and, more so, of the central nervous system. Several studies revealed that n-3 PUFAs possess anti-inflammatory actions and are useful in the treatment of dyslipidemia. These actions explain the beneficial actions of n-3 PUFAs in the management of cardiovascular diseases, inflammatory conditions, neuronal dysfunction, and cancer. But, the exact molecular targets of these beneficial actions of n-3 PUFAs are not known. Mice engineered to carry a fat-1 gene from Caenorhabditis elegans add a double bond into an unsaturated fatty acid hydrocarbon chain and convert n-6 to n-3 fatty acids. This results in an abundance of n-3 eicosapentaenoic acid and docosapentaenoic acid specifically in the brain and a reduction in n-6 fatty acids of these mice that can be used to evaluate the actions of n-3 PUFAs. Gene expression profile, RT-PCR and protein microarray studies in the hippocampus and whole brain of wild-type and fat-1 transgenic mice revealed that genes and proteins concerned with inflammation, apoptosis, neurotransmission, and neuronal growth and synapse formation are specifically modulated in fat-1 mice. These results may explain as to why n-3 PUFAs are of benefit in the prevention and treatment of diseases such as Alzheimer's disease, schizophrenia and other diseases associated with neuronal dysfunction, low-grade systemic inflammatory conditions, and bronchial asthma. Based on these data, it is evident that n-3 PUFAs act to modulate specific genes and formation of their protein products and thus, bring about their various beneficial actions.