Effect of nickel on aromatic amino acids and biogenic amines in brain of guinea pigs

Nickel chloride was administered daily for 60 days to male guinea pigs. The levels of tyrosine and tryptophan were increased in both serum and brain after this treatment. Brain dopamine levels increased by 18%, but norepinephrine (NE), 5-hydroxytryptamine (5-HT) and their metabolites did not show significant change. The increased level of dopamine induced by nickel may be of significance in view of evidence that metal ions play a rôle in the metabolism of brain biogenic amines.     

Effects of acute and chronic phenelzine on regional monoamine metabolism in rats and its potentiation by deuterium substitution

Summary Phenelzine is a monoamine oxidase inhibitor with antidepressant properties. The present study investigated effects of acute (1–2 mg kg^–1 4h s.c.) and chronic (0.25–2 mg kg^–1 day^–1 Alzet miniosmotic pumps, 13 days s.c.) administration of phenelzine on regional monoamine metabolism in rats. The effects of these phenelzine treatments were compared with those of equivalent doses of a deuterated form of the drug (phenelzine-d₄). The following brain regions and compounds were assessed using high performance lipuid chromatography with electrochemical detection: Striatum: dopamine, DOPAC, HVA, 5-HT, 5-HIAA; hypothalamus: dopamine, 5-HT, 5-HIAA, noradrenaline; hippocampus: 5-HT, 5-HIAA, noradrenaline; frontal cortex: dopamine, noradrenaline, 5-HT, 5-HIAA. Acute drug administration increased levels of dopamine, 5-HT and noradrenaline with the exception of dopamine in the hypothalamus and frontal cortex and 5-HT in the hypothalamus. DOPAC, HVA and 5-HIAA levels were decreased. After chronic administration amine levels increased with the exception of dopamine administration amine levels increased with the exception of dopamine in the hypothalamus. The respective acid metabolites were also decreased. These effects of phenelzine were markedly potentiated by deuterium which was substituted for hydrogen in the side chain. The potentiation of these effects was enhanced with chronic administration, differences between phenelzine and phenelzine-d₄ effects being more marked at lower doses.     

The effect of alcoholism on salsolinol and biogenic amines in human brain

Chronic alcoholics with a well documented history of alcohol abuse were divided at autopsy into two groups, intoxicated alcoholics (IA, with blood ethanol levels) and sober alcoholics (SA, without blood ethanol levels). Norepinephrine (NE), 4-hydroxy-3-methoxyphenyl-glycol (HMPG), 5-hydroxyindoleacetic acid (5-HIAA), dopamine (DA), salsolinol (SAL) and methylated salsolinol (M-SAL) in caudate nucleus and putamen from the two groups of alcoholics and an age-matched control group were analysed with gas chromatography-mass spectrometry. HMPG was significantly increased in the brains of the alcoholics compared to controls (IA, P less than 0.001 and SA, P less than 0.05) indicating an increased NE turnover in the brains of alcoholics. 5-HIAA, the major 5-hydroxytryptophan (5-HT) metabolite, was increased in the caudate nucleus from SA (P less than 0.05) compared to controls and IA. This could be interpreted as an increased turnover of 5-HT at abstinence. SAL can be formed from DA and acetaldehyde and/or pyruvate. SAL was found in all brains studied. The levels were about 1% of the dopamine concentrations. SAL had a tendency to be increased in brains of IA compared to control brains. The most remarkable finding was that SAL was significantly decreased in both the caudate nucleus and putamen from SA compared to controls and IA. M-SAL showed tendencies in the same directions as SAL. DA did not show any significant changes, but tended to be lower in SA.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of ultrafine diesel exhaust particles on oxidative stress generation and dopamine metabolism in PC-12 cells

A major constituent of urban air pollution is diesel exhaust, a complex mixture of gases, chemicals, and particles. Recent evidence suggests that exposure to air pollution can increase the risk of a fatal stroke, cause cerebrovascular damage, and induce neuroinflammation and oxidative stress that may trigger neurodegenerative diseases, such as Parkinson's disease. The specific aim of this study was to determine whether ultrafine diesel exhaust particles (DEPs), the particle component of exhaust from diesel engines, can induce oxidative stress and effect dopamine metabolism in PC-12 cells. After 24 h exposure to DEPs of 200 nm or smaller, cell viability, ROS and nitric oxide (NO₂) generation, and levels of dopamine (DA) and its metabolites, (dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)), were evaluated. Results indicated cell viability was not significantly changed by DEP exposure. However, ROS showed dramatic dose-dependent changes after DEP exposure (2.4 fold increase compared to control at 200 μg/mL). NO₂ levels were also dose-dependently increased after DEP exposure. Although not in a dose-dependent manner, upon DEP exposure, intracellular DA levels were increased while DOPAC and HVA levels decreased when compared to control. Results suggest that ultrafine DEPs lead to dopamine accumulation in the cytoplasm of PC-12 cells, possibly contributing to ROS formation. Further studies are warranted to elucidate this mechanism.