Neurotransmitter and carbohydrate metabolism during aging and mild hypoxia

Alterations in the metabolism of the glucose derived neurotransmitters may underlie some of the deficits in brain function that can accompany aging. We examined the whole brain syntheses of acetylcholine (ACh), alanine, aspartate, glutamate, gamma-aminobutyrate (GABA), glutamine and serine in two strains (C57BL and BALB/c) of aged mice (3, 10 and 30 months). ACh synthesis in C57BL and BALB/c mice declined 41 and 44% at 10 months and 64 and 75% by 30 months. Incorporation of [U-14C]glucose into amino acids generally decreased with aging, but it was not depressed as much as ACh formation. The only significant reductions in the amino acids in the 30 month old mice of both strains were in the syntheses of GABA (46 and 32%) and glutamine (44 and 55%). These changes may make the aged brain more vulnerable to metabolic insults, since mild anemic hypoxia decreased the syntheses of all the neurotransmitters at all ages even further. ACh synthesis in hypoxic 30 month old mice was only 9-11% of the 3 month old nonhypoxic mice, whereas amino acid formation ranged from 18-55% of the 3 month old nonhypoxic mice. Carbohydrate metabolism and its response to metabolic insults was also altered by age in both strains. The 30 month old mice had higher brain lactate concentrations than the 3 month old mice. The combination of hypoxia and aging further depressed oxidative metabolism, since a greater increase in brain lactates occurred in the aged hypoxilism and its response to metabolic insults was also altered by age in both strains. The 30 month old mice had higher brain lactate concentrations than the 3 month old mice. The combination of hypoxia and aging further depressed oxidative metabolism, since a greater increase in brain lactates occurred in the aged hypoxilism and its response to metabolic insults was also altered by age in both strains. The 30 month old mice had higher brain lactate concentrations than the 3 month old mice. The combination of hypoxia and aging further depressed oxidative metabolism, since a greater increase in brain lactates occurred in the aged hypoxic mice than in young hypoxic mice. Thus, aging may reduce the ability of the brain to adapt to metabolic insults.