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

F. Kuperstein, E. Yakubov, P. Dinerman, S. Gil, R. Eylam, N. Salem, Ephraim Yavin

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

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 α-2 and α-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.

Original languageEnglish (US)
Pages (from-to)1550-1562
Number of pages13
JournalJournal of Neurochemistry
Volume95
Issue number6
DOIs
StatePublished - Dec 2005

Keywords

  • Attention deficit hyperactivity disorder
  • Docosahexaenoic acid deficiency
  • Dopamine receptors
  • Gene array
  • Genomic markers
  • Suppression subtractive hybridization

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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