title: Induction of the immediate early gene c-jun in human spinal cord in amyotrophic lateral sclerosis with concomitant loss of NMDA receptor NR-1 and glycine transporter mRNA.
abstract: The aetiology of the sporadic form of amyotrophic lateral sclerosis (ALS) is poorly understood although abnormalities in glutamate and glycine transport have been implicated which both could contribute to a neurodegenerative process mediated through the N-methyl-D-aspartate (NMDA) receptor. In this study we have used in situ hybridization to investigate whether any changes in the expression of NMDA receptors, the glycine transporter or glutamate-mediated injury responses are detectable in ALS. Two immediate early genes were investigated as markers of neuronal injury responses, c-jun and zif-268, both constitutively expressed in the spinal cord. Levels of c-jun mRNA were most abundant in intermediate grey and layer IX of the ventral horn containing motor neurones. This pattern was markedly changed in ALS with large increases (2-3 fold) in c-jun mRNA occurring in dorsal and ventral horn. The marked increase in c-jun mRNA was also substantiated by slot blot analysis of tissue homogenates of spinal cord and a parallel induction of zif-268 mRNA was also seen. NMDA receptor NR-1 mRNA was widely distributed in control spinal cord with the highest concentrations occurring in layers IX, X, intermediate grey and dorsal horn. The ALS cases showed a selective decrease in the level of NR-1 mRNA in the ventral region (50%) whilst no significant decrease was detected in the dorsal region. Quantitation of tissue homogenates with dorsal and ventral regions combined also yielded a significant decrease of 40% which supports the analysis from in situ hybridization densitometry.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Biochemistry, Charing Cross and Westminster Medical School, London, UK.
authors.forename: L
authors.initials: L
authors.lastname: Virgo
authors.forename: J
authors.initials: J
authors.lastname: de Belleroche
mesh_terms: D000328:Adult; D000368:Aged; D026921:Amino Acid Transport Systems, Neutral; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018076:DNA, Complementary; D005260:Female; D017781:Genes, Immediate-Early / Q000235:genetics; D005998:Glycine / Q000235:genetics / Q000378:metabolism*; D050487:Glycine Plasma Membrane Transport Proteins; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism*
chemical_list: D026921:Amino Acid Transport Systems, Neutral; D002352:Carrier Proteins; D018076:DNA, Complementary; D050487:Glycine Plasma Membrane Transport Proteins; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D005998:Glycine