Overexpression of dopamine receptor genes and their products in the postnatal rat brain following maternal n-3 fatty acid dietary deficiency

J Neurochem. 2005 Dec;95(6):1550-62. doi: 10.1111/j.1471-4159.2005.03513.x. Epub 2005 Nov 23.


A combination of PCR-Select cDNA subtraction and gene array hybridization was used to identify differentially expressed genomic markers in brains of rats fed for 3 weeks in utero and 2 weeks after birth on an n-3 polyunsaturated fatty acid (PUFA)-deficient diet supplied to dams. Total RNA was isolated, switch mechanism at 5'-end of the RNA transcripts (SMART) applied and used for PCR-Select subtraction of PUFA-deficient and adequately-fed control preparations. Subtracted and amplified ds-cDNA end-products were fragmented, terminally labeled with biotin-ddUTP and hybridized with a RN-U34A gene array. A 10-fold increase in potential genes with log2(Tester/Driver) = 1.4 was found compared with traditional gene array technology when the same chip was tested using non-subtracted targets. Reverse transcription-real-time relative PCR confirmed 30% of the transcripts. Among the validated transcripts, D1 and D2 receptors for dopamine (DA), were most prominent among a number of over-expressed neurotransmitter receptors and retinoic acid receptor (RXR alpha-2 and alpha-1). Immunohistochemical staining of brain sections from 2-week-old pups revealed a substantial enrichment of the D2 receptor in discrete regions of the mesolimbic and mesocortical pathways as well as in a large number of brain areas from the n-3 PUFA-deficient pups. Punches of the same areas run on western blots showed similar results. The overwhelming expression of D1 and D2 receptors may be attributed to a behavioral hypersensitivity caused by the possible impairment of DA production during brain development, which may have implications in certain disorders of the nervous system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn / physiology*
  • Blotting, Western
  • Brain Chemistry / genetics*
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / physiology
  • DNA, Complementary / biosynthesis
  • Diet
  • Fatty Acids / administration & dosage
  • Fatty Acids, Omega-3 / physiology*
  • Female
  • Gene Expression / physiology
  • Gene Expression Regulation
  • Gene Library
  • Immunohistochemistry
  • In Situ Hybridization
  • Limbic System / metabolism
  • Limbic System / physiology
  • Nerve Tissue Proteins / metabolism
  • Oligonucleotide Array Sequence Analysis
  • RNA / biosynthesis
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Dopamine / biosynthesis*
  • Receptors, Dopamine / genetics*
  • Receptors, Dopamine D1 / physiology
  • Receptors, Dopamine D2 / physiology
  • Reverse Transcriptase Polymerase Chain Reaction


  • DNA, Complementary
  • Fatty Acids
  • Fatty Acids, Omega-3
  • Nerve Tissue Proteins
  • Receptors, Dopamine
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • RNA