The effects of aging on levels of neurotransmitters were determined in two regions of the cerebral cortex in rhesus monkeys (Macaca mulatta). Choline acetyltransferase (ChAT) activity as well as somatostatin, neuropeptide Y, and substance P immunoreactivities were analyzed in the right caudal cingulate gyrus and in the left and right inferior occipital poles in five age groups: 4-6 years; 8-11 years; 20-25 years; 26-29 years; and 31-34 years. Neuroactive amino acids and markers for monoamine transmitters were analyzed only in the youngest (4-6 years) and oldest (31-34 years) animals. Across the five age groups studied. ChAT activity as well as somatostatin and neuropeptide Y immunoreactivities were significantly decreased bilaterally in occipital poles of the 31- to 34-year-old group. There were no significant age-related differences in substance P immunoreactivity. In 4-6-year-old vs. 31-34-year-old monkeys, levels of amino acid neurotransmitters were unchanged. However, there were significant reductions in norepinephrine, serotonin and its metabolites, kynurenine, and 4-hydroxyphenyllactic acid in occipital poles of the 31- to 34-year-old monkeys. No significant neurochemical changes were detected in the cingulate cortex. These findings demonstrate that aged nonhuman primates show reductions in cortical markers for a variety of neurotransmitters, including acetylcholine, somatostatin, neuropeptide Y, norepinephrine, and serotonin but that these changes do not occur uniformly in the neocortex.

Aging↗

PubMedDate not supplied

Blockade of 1-methyl-4-phenylpyridinium ion (MPP+) nigral toxicity in the rat by prior decortication or MK-801 treatment: a stereological estimate of neuronal loss.

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, (MPTP), produces a parkinsonian syndrome both in man and in experimental animals. Its toxicity is mediated by a metabolite, the 1-methyl-4-phenylpyridinium ion (MPP+). When injected into the striatum, MPP+ is accumulated by dopaminergic nerve terminals and retrogradely transported to the substantia nigra pars compacta (SNc) where it causes neuronal degeneration. MPP+ accumulates in mitochondria and blocks complex I of the electron transport chain. A proposed mechanism of neurotoxicity is excitotoxic neuronal degeneration induced by this energy depletion. We examined whether either prior decortication or administration of the N-methyl-D-aspartate (NMDA) receptor antagonist, (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801) could prevent or diminish the selective nigral neuronal degeneration that follows unilateral intrastriatal injection of MPP+. We quantified the extent of neuronal death in the SNc ipsilateral and contralateral to the injections on Nissl-stained sections with unbiased stereological techniques. One week after injection of MPP+, approximately 75% of the SNc neurons were lost on the side of the injection. The loss was a consequence of the reduction in both SNc volume and neuronal density. Both prior decortication or the administration of MK-801 for 2 days nearly completely prevented MPP(+)-induced neuronal loss in the ipsilateral SNc. These results are consistent with an NMDA receptor mediated excitotoxic mechanism for MPP(+)-induced nigral toxicity.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗