Expression of the Genes Coding for Ornithine Decarboxylase and Its Regulatory Protein Antizyme in the Developing Rat Brain

Abstract

The ontogenic expression of the genes coding for ornithine decarboxylase (ODC) and its inhibitory protein, antizyme (AZ), was studied in the rat brain between embryonic day (E) 16 and postnatal day (P) 66. The level of ODC mRNA in whole brain was maximal at P2 and rapidly declined by P7 to a low level that was maintained into the adult. Levels of AZ mRNA also peaked at P2, and high levels were sustained into the adult. Regional studies indicated that between P2 and P60 ODC mRNA levels declined in the cerebral cortex, hippocampus and brainstem. These changes reflect the ontogenic pattern of protein levels and enzyme activity suggesting control of this enzyme may occur at the level of transcription. The level of AZ mRNA markedly increased in the cerebellum between P10 and P60. The level of ODC and AZ mRNA at P5 was not altered after continuous suppression of ODC enzyme activity by a-difluoromemylornithine between P0 and P5. This suggests that ODC gene expression is not subject to product-related feedback inhibition during this period. Immunohistochemical localisation of ODC protein at P5 revealed ubiquitous distribution of immunoreactivity with higher levels in the hippocampus, cerebral cortex and discrete nuclei in the brainstem. ODC protein was undetectable in the adult rat brain.

Antizyme Inhibitor 2-Deficient Mice Exhibit Altered Brain Polyamine Levels and Reduced Locomotor Activity

“…On the other hand, the levels of Odc mRNA showed a gradual decrease, reaching low levels at day seventeen, followed by an increase from day twenty that remained increasing until day sixty. These results agree with previous studies, where discrepancies between ODC and Odc mRNA levels were observed during brain development [17,33], suggesting the post-transcriptional or translational regulation of ODC activity in the brain. Since antizymes negatively affect ODC, the fall in ODC activity found during the postnatal period may be related to the increase in the expression of both Az1 and Az2.…”

“…Many studies have demonstrated the existence of ODC in the brain of adult rats and mice, as well as important changes in its activity during brain development [16][17][18]. However, less is known about the expression and function of their regulatory proteins AZs and AZINs in the brain.…”

Inward-Rectifying Potassium (Kir) Channels Regulate Pacemaker Activity in Spinal Nociceptive Circuits during Early Life

“…The polyamines spermine and spermidine block K ir channels with a much higher (10-to-100 fold) potency than Mg 2+ (Lopatin et al, 1994; Fakler et al, 1995) and are highly expressed within lamina I of the spinal cord (Laube et al, 2002), where they are synthesized from the amino acids arginine and methionine via the activation of ornithine decarboxylase (Tabor and Tabor, 1984). Interestingly, ornithine decarboxylase expression in the rat brain is highest at birth and declines rapidly during the first week of life (Pujic et al, 1995). In addition, polyamine levels in the CNS can be modulated by sensory experience during development (Aizenman et al, 2002).…”

Expression of ODC and its regulatory protein antizyme in the adult rat brain

“…A few immunohistochemical studies on ODC expression in CNS have been published since the first demonstration of the ODC-immunoreactivity in CNS neurons (Cintra et al, 1987), but these have focused on the developmental pattern of expression (Dorn et al, 1987;Müller et al, 1993) or on the effect of pathological stimuli on expression (Müller et al, 1991;Bernstein and Müller, 1995;Ichikawa et al, 1997). ODC and Az expression has been compared only in rat motoneurons (Junttila et al, 1995) using immunocytochemistry and in the developing rat brain using in situ hybridization (Pujic et al, 1995). The present study provides for the first time detailed and comparative information about ODC and Az expression in the adult mammalian brain.…”