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

Prostaglandins Leukot Essent Fatty Acids. 2009 Jan;80(1):33-42. doi: 10.1016/j.plefa.2008.11.006. Epub 2009 Jan 9.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / anatomy & histology
  • Brain / metabolism*
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins* / genetics
  • Caenorhabditis elegans Proteins* / metabolism
  • Fatty Acid Desaturases* / genetics
  • Fatty Acid Desaturases* / metabolism
  • Fatty Acids, Unsaturated / chemistry
  • Fatty Acids, Unsaturated / metabolism
  • Gene Expression Profiling*
  • Gene Expression Regulation
  • Male
  • Mice
  • Mice, Transgenic
  • Oligonucleotide Array Sequence Analysis*
  • Protein Array Analysis*

Substances

  • Caenorhabditis elegans Proteins
  • Fatty Acids, Unsaturated
  • fat-1 protein, C elegans
  • Fatty Acid Desaturases