Ornithine Decarboxylase in Human Brain: Influence of Aging, Regional Distribution, and Alzheimer's Disease

Abstract

Although experimental animal data have implicated ornithine decarboxylase, a key regulatory enzyme of polyamine biosynthesis, in brain development and function, little information is available on this enzyme in normal or abnormal human brain. We examined the influence, in autopsied human brain, of postnatal development and aging, regional distribution, and Alzheimer's disease on the activity of ornithine decarboxylase. Consistent with animal data, human brain ornithine decarboxylase activity was highest in the perinatal period, declining sharply (by '-60%) during the first year of life to values that remained generally unchanged up to senescence. In adult brain, a moderately heterogeneous regional distribution of enzyme activity was observed, with high levels in the thalamus and occipital cortex and low levels in cerebellar cortex and putamen. In the Alzheimer's disease group, mean ornithine decarboxylase activity was significantly increased in the temporal cortex (+76%), reduced in occipital cortex(-70%), and unchanged in hippocampus and putamen. In contrast, brain enzyme activity was normal in patients with the neurodegenerative disorder spinocerebellar ataxia type I. Our demonstration of ornithine decarboxylase activity in neonatal and adult human brain suggests roles for ornithine decarboxylase in both developing and mature brain function, and we provide further evidence for the involvement of abnormal polyamine system activity in Alzheimer's disease. Key Words: Human brain-Ornithine decarboxylase-Polyamine system-Development-Aging -Alzheimer's disease.

Cellular Polyamines Promote the Aggregation of α-Synuclein

“…Polyamines in Neurodegeneration and Neuroprotection-The concentrations of polyamines are maintained during neurodegeneration associated with PD and AD (37), although the activities of ornithine decarboxylase and spermidine/spermidine acetyl transferase, the key enzymes in the biosynthetic pathway of polyamines, increase significantly (39,60). Polyamines are scavengers for free radicals and protect cells from free radical-induced oxidative damage, a process that promotes aggregation of ␣-synuclein (21,61).…”

“…Spermine may serve to protect neuronal cells from oxidative stress (38), a condition known to induce aggregation of the amyloid A␤ peptide, the major component of amyloid deposits associated with Alzheimer's disease. It was also shown in cultured neuronal cells that the A␤ peptide combined with spermine is more toxic than the peptide alone (39). A possible role for these cations in the aggregation of ␣-synuclein has not been proposed.…”

Developmental Neurotoxicity of Toluene in Rats as Measured by L‐Ornithine Decarboxylase in Cerebellum

“…It seems to be so that whenever tissue is growing or differentiating, increased ornithine decarboxylase activity and consequently a high polyamine concentrations are observed. Ornithine decarboxylase activity is highest around the day of birth and then steadily declines in the progressively developing nervous system, which has been shown in cerebellar granule neurones from rats (Sparapani et al 1998), in cerebral cortices from rats (Ichikawa et al 1997(Ichikawa et al & 1998 and in cerebellar cortices from man (Morrison et al 1998). A more recent study systematically analyses the age variation in rat brain activity, and the highest activity was shown at gestational day 19, followed by a sharp decline in the progressively developing brain (Lam et al 2002).…”

Disrupted Spermine Homeostasis: A Novel Mechanism in Polyglutamine-Mediated Aggregation and Cell Death

“…8). Despite disruption of synthetic pathways, changes in intracellular spermine levels are difficult to observe because of multilevel homeostatic mechanisms controlling spermine concentrations (Porter et al, 1990;Halmekyto et al, 1991;Fogel-Petrovic et al, 1996;Hayashi et al, 1996;Pietila et al, 1997;Morrison et al, 1998;Kepka-Lenhart et al, 2000;Suppola et al, 2001). SSAT, the enzyme that catalyzes the back-conversion of spermine to N-acetyl forms, is tightly regulated by intracellular spermine.…”