Polyamines in Human Brain: Regional Distribution and Influence of Aging

Abstract

Although much evidence has implicated polyamines in brain development and function, little information is available on these substances in human brain. We examined the influence of regional distribution and aging on putrescine, spermidine, and spermine levels in autopsied human brain. In the adult brain, concentrations of spermidine were the highest, followed by spermine and putrescine. All three polyamines showed a distinct and uneven distribution profile among the 10 examined brain areas. Spermidine levels were especially high in white matter and thalamus (20 and 9.3 nmol/mg of protein, respectively), whereas spermine concentrations were highest in cerebellar cortex (3.4 nmol/mg of protein). High levels of putrescine were observed in cerebral cortices, putamen, and hippocampus (0.7–1.2 nmol/mg of protein), with lowest levels in cerebellum and thalamus (0.3–0.5 nmol/mg of protein). No statistically significant influence of aging (1 day to 103 years; n = 57) on either putrescine or spermine levels in occipital cortex was observed. In contrast, spermidine levels increased markedly from birth, reaching maximal levels at ∼40 years of age (+228% increase in the mean 41‐year‐old group vs. 6‐week‐old group), which were maintained up to senescence. These observations in human brain thus differ from those reported in the rodent, in which levels of all three polyamines show a pronounced postnatal reduction. Our data support the notion that polyamines may have roles in both postnatal brain development and in mature brain function.

Safety and tolerability of spermidine supplementation in mice and older adults with subjective cognitive decline

“…Concentration of polyamines in the body is sustained by endogenous biosynthesis, microbial activity in the intestines, and exogenous food intake. However, it has been shown that intracellular polyamine concentrations of several organs decline with age in animals [2] and humans [3-6]. …”

Systemic administration of polyaminergic agents modulate fear conditioning in rats

“…The polyamines putrescine, spermine, and spermidine are present in almost all cells but at particularly high concentrations in the vertebrate nervous system, including cerebral structures known to participate in memory formation, such as the amygdala and hippocampus (Morrison et al 1995). In fact, electrophysiological and neurochemical evidence suggest that polyamines modulate α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (Pellegrini-Giampietro 2003;Stromgaard and Mellor 2004) and N-methyl-Daspartate (NMDA) receptors (McGurk et al 1990; Ransom and Stec 1988;Sacaan and Johnson 1990;Sprosen and Woodruff 1990), which are excitatory ionotropic glutamate receptors implicated in learning and memory (Cammarota et al 2004;Izquierdo et al 2000;Jasnow et al 2004;Sprosen and Woodruff 1990;Stote and Fanselow 2004).…”

Maintained regulation of polyamines in spinal cord from patients with amyotrophic lateral sclerosis

“…Polyamines have also been found to be stable over a 24-h postmortem period at + 4 jC in whole rat brain [39].…”

“…Studies of the effect of aging on polyamine levels in human brain have shown a slow decrease in the concentration of spermidine after the fifth decade of life with no significant changes in the levels of putrescine and spermine [38,39]. In the rat brain, no significant differences in polyamine levels have been found between adult and aged animals, whereas in spinal cord, significantly higher levels of putrescine and spermidine were found in the aged rats [42].…”