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1.
To investigate the hypothesis that manganese toxicity may affect the development of the monoamine oxidases (MAOs) in brain, the regional distributions of the A (serotonin-oxidizing) and B (benzylamine-oxidizing) forms of MAO were determined in manganese-treated (1 mg or 10 mg of MnCl2·4H2O per ml of drinking water from conception onwards until the rats were used for experiments) and untreated male rats during various stages of postnatal development. The age-related variations in regional M AO-A activities (especially in pons and medulla and in cerebellum) were more marked than those in regional MAO-B activities. The MAO-A:MAO-B activity ratios decreased in all regions during development. Chronic manganese treatment (at the specified doses) did not significantly alter the age-related changes in regional MAO-A and MAO-B activities; nor were the A:B activity ratios affected. The results suggest that there is differential expression of MAO isoforms in various brain regions during postnatal development but the expression is not affected by chronic manganese toxicity. 相似文献
2.
To investigate the hypothesis that neurotoxic metals can exert their toxicity through the direct inhibition of monoamine oxidases (MAOs), the effects of several neurotoxic metal ions on type A (MAO-A) and type B (MAO-B) monoamine oxidase activities in rat forebrain nonsynaptic mitochondria and rat liver mitochondria were studied. At pathophysiological levels (10–100 M), Cu2+ and Cd2+ are good inhibitors of brain mitochondrial MAO-A and, to a lesser extent, liver mitochondrial MAO-A. The inhibition of MAO-B activities in brain and liver mitochondria by Cu2+ and Cd2+ is only detected at the higher end of the concentration range (i.e., 50–100 M). At the pathophysiological level of 0.5 mM, Al3+ only inhibits brain mitochondrial MAO-A but at the higher level of 2.5 mM, it inhibits both forms of MAO in brain as well as liver mitochondria. Even at toxic levels (e.g., 5 mM), neither Mn2+ nor Li+ inhibits the activities of MAO-A and MAO-B in brain and liver mitochondria. Our results are consistent with the hypothesis that some neurotoxic metals can exert their toxicity through the direct inhibition of the isoforms of MAO. Our data also suggest that the selective inhibition of brain MAO-A by Cu2+ and Cd2+ may assume pathophysiological importance in the neurotoxicity of copper and cadmium. 相似文献
3.
Endogenous GLP‐1 alters postprandial functional connectivity between homeostatic and reward‐related brain regions involved in regulation of appetite in healthy lean males: A pilotstudy
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Anne Christin Meyer‐Gerspach PhD Huynh Giao Ly PhD Stefan Borgwardt MD Patrick Dupont MD Christoph Beglinger MD Lukas Van Oudenhove MD Bettina K. Wölnerhanssen MD 《Diabetes, obesity & metabolism》2018,20(10):2330-2338
4.
Effect of dehydroepiandrosterone (DHEA) on monoamine oxidase activity,lipid peroxidation and lipofuscin accumulation in aging rat brain regions 总被引:1,自引:1,他引:1
Dehydroepiandrosterone (DHEA), one of the major steroid hormones, and its ester have recently received attention with regard to aging and age-related diseases like Alzheimer and others. DHEA is synthesized de novo in the brain and its substantial fall with age has been shown to be associated with neuronal vulnerability to neurotoxicity processes. Thus, DHEA is considered to be a neuroactive pharmacological substance with potential antiaging properties. A prominent feature that accompanies aging is an increase in monoamine oxidase (MAO). Increased MAO activity with correlated increase in lipid peroxidation in the aging rat brain supports the hypothesis that catecholamine oxidation is an important source of oxidative stress. The progressive accumulation of lipofuscin in neuronal cells is one of the most characteristic age related changes, an increase in body weight was also observed at 24 months. The objective of this study was to observe the changes in monoamine oxidase activity, lipid peroxidation levels and lipofuscin accumulation occurring in aging rat brain regions, and to see whether these changes are restored to normal levels after exogenous administration of DHEA (30 mg/kg/day for 1 month). The results obtained in the present work revealed that normal aging was associated with significant increases in the activity of monoamine oxidase, lipid peroxidation levels and lipofuscin accumulation in brain regions of 4, 14 and 24 months age group male rats. The present study showed that DHEA treatment significantly decreased monoamine oxidase activity, lipid peroxidation and lipofuscin accumulation in brain regions of aging rats, the increased body weight at 24 months also decreased more than the age matched controls. It can therefore be suggested that DHEA's beneficial effects seemed to arise from its antioxidant, antiobesity, antilipofuscin, antilipidperoxidative and thereby anti-aging actions. The results of this study will be useful for pharmacological modification of the aging process and development of new drugs for age related disorders. 相似文献
5.
The effects of in vitro treatment with ammonium chloride, hepatic encephalopathy (HE) due to thioacetamide (TAA) induced liver failure and chronic hyperammonemia produced by i. p. administration of ammonium acetate on the activity of the two malate-aspartate shuttle enzymes: aspartate aminotransferase (AAT), malate dehydrogenase (MDH), and on the pyruvate carboxylase (PC) activity were examined in synaptic and nonsynaptic mitochondria from rat brain. With regard to the shuttle enzymes the response to ammonium ions in vitro (3mM NH4Cl) was observed in nonsynaptic mitochondria only, and was manifested by a 27% decrease of AAT activity and a 16% decrease of MDH activity. By contrast, both in vivo conditions primarily affected the synaptic mitochondrial enzymes: TAA-induced HE produced a 26% decrease of synaptic mitochondrial AAT and a 50% decrease of synaptic mitochondrial MDH. Hyperammonemia inhibited synaptic mitochondrial AAT by 30% and synaptic mitochondrial MDH by 45%. HE produced no effect at all in nonsynaptic mitochondria while hyperammonemia produced a 30% increase in the AAT activity, but no changes in MDH. All the experimental conditions affected the nonsynaptic mitochondrial PC: ammonium chloride in vitro produced a 20% decrease, TAA-induced HE — a 30% decrease, whereas hyperammonemia inhibited the enzyme by 53%. The PC activity in synaptic mitochondria was very low (about 2% of that measured in nonsynaptic mitochondria), which is consistent with the primarily astrocytic localization of the enzyme. 相似文献
6.
Circadian variations in the monoamine levels and monoamine oxidase activity in different regions of the rat brain as a function of age 总被引:1,自引:0,他引:1
Time-related changes in the levels of norepinephrine (NE), dopamine (DA), 5-hydroxytryptamine (5-HT) and monoamine oxidase (EC 1.4.3.4, MAO) activity have been studied in the cerebral cortex, cerebellum, medulla oblongata, hypothalamus, striatum and midbrain of 21 day, 3, 6, 12 and 24 month old rats maintained at 12 hours of light and 12 hours of dark condition. Maximum NE level was seen during the dark phase in all the regions of 3, 6, 12 and 24 month old rats, whereas in 21 day old, the maximum NE level occurred during the light phase. In the cerebral cortex and in the cerebellum of 21 day old rat DA was absent at all times. In all the other age groups, the maximum DA level was seen during the dark phase, while for 5-HT higher level was during the light phase in all the age groups. MAO activity of 3, 6, 12 and 24 month old rats showed the peak activity at the beginning of the light phase (06:00 hours), whereas cerebral cortex, cerebellum and medulla oblongata of 21 day old rat had its peak MAO activity at 14:00 hours and at 22:00 hours in other regions. 相似文献
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Van Der Sanden MJ Nagy K Semsei I Zs -Nagy I 《Archives of gerontology and geriatrics》1995,20(3):273-282
The enzyme activities of trypsin (using an artificial substrate, Nalpha-benzoyl-L-arginine-ethylester = BAEE), xanthine oxidase (XOD) and superoxide dismutase (SOD) were measured in the absence and presence of various concentrations of the following inert, water-soluble polymer viscogens: polyvinylpyrrolidone (PVP-40), polyethyleneglycol (PEG-6000) and bovine serum albumin (BSA). Enzyme activities measured in the absence of viscogens were taken as 100%. In the presence of the viscogens, enzyme activities decreased considerably as follows: (i) Trypsin: to 2 or 12% in reaction mixtures containing 64 mg/ml PVP-40 or 481 mg/ml PEG-6000, respectively. (ii) XOD: to 29.3% in a reaction mixture containing 116 mg/ml PVP-40, to 68.9% in a medium containing 266 mg/ml PEG-6000, and 38.1% in the presence of 138 mg/ml BSA. (iii) SOD: to 40.0, 19.9 and 16.6% in the same media as listed for XOD, respectively. The observations are consistent with the predictions of the molecular enzyme kinetic model (MEKM), and are also of importance for the membrane hypothesis of aging, since the latter explains the loss of cell functions by an age-dependent increase of intracellular density which may cause serious enzyme inhibitions. 相似文献
9.
Blumenau C Berger E Fauteck JD Madeja M Wittkowski W Speckmann EJ Musshoff U 《Journal of pineal research》2001,30(3):139-146
Melatonin-sensitive receptors were expressed in Xenopus laevis oocytes following an injection of mRNA from rat brain. The administration of 0.1-100 micromol/L melatonin to voltage-clamped oocytes activates calcium-dependent chloride currents via a pertussis toxin-sensitive G protein and the phosphoinositol pathway. To determine which melatonin receptor type (mt1, MT2, MT3) is functionally expressed in the Xenopus oocytes, we used (i) agonists and antagonists of different receptor types to characterize the pharmacological profile of the expressed receptors and (ii) a strategy of inhibiting melatonin receptor function by antisense oligonucleotides. During pharmacological screening administration of the agonists 2-iodomelatonin and 2-iodo-N-butanoyl-5-methoxytryptamine (IbMT) to the oocytes resulted in oscillatory membrane currents, whereas the administration of the MT3 agonist 5-methoxycarbonylamino-N-acetyltryptamine (GR135,531) exerted no detectable membrane currents. The melatonin response was abolished by a preceding administration of the antagonists 2-phenylmelatonin and luzindole but was unaffected by the MT3 antagonist prazosin and the MT2 antagonist 4-phenyl-2-propionamidotetralin (4-P-PDOT). In the antisense experiments, in the control group the melatonin response occurred in 45 of 54 mRNA-injected oocytes (83%). Co-injection of the antisense oligonucleotide, corresponding to the mt1 receptor mRNA, caused a marked and significant reduction in the expression level (13%; P < 0.001). In conclusion, the results demonstrate that injection of mRNA from rat brain in Xenopus oocytes induced the expression of the mt1 receptor which is coupled to the phosphoinositol pathway. 相似文献
10.
Maria-Cristina Carrillo Kenichi Kitani Chiyoko Minami Wakako Maruyama 《Geriatrics & Gerontology International》2007,7(3):279-284
Objective: Age-related changes in endogenous antioxidant enzyme activities have been widely discussed in relation to mechanisms of organismic aging. However, some discrepancies in this regard can be seen in the published work. The present study aimed to clarify past discrepancies using BN/Bi rats in which no study has been reported in the past.
Methods: Antioxidant enzyme activities such as superoxide dismutase (SOD) and catalase (CAT) were compared in several brain regions and the liver between young (8–9 months) and old (27–29 months) BN/BiRijHsd rats of both sexes.
Results: CAT activities in brain regions were quite comparable between young and old rats of both sexes. SOD activity changes with age also were not remarkable, with the exception of significantly lower Mn-SOD activities in substantia nigra and hippocampus of old male rats and significantly higher activities of Cu/Zn-SOD in substantia nigra of old female rats in comparison with respective values in young rats. CAT activities in the liver tended to be lower in old male rats, while in females the opposite was observed. SOD activities in the liver stayed essentially unchanged with age in males, while in females total as well as Cu/Zn-SOD activities were more than twofold higher in old animals.
Conclusion: These data coupled with previously reported results, indicate that no generalization can be made in terms of age-related changes in antioxidant enzyme activities. These differences emphasize the need of "public observations" in any attempt to generate a theory for mechanisms of aging based on antioxidant enzyme activity changes with age. 相似文献
Methods: Antioxidant enzyme activities such as superoxide dismutase (SOD) and catalase (CAT) were compared in several brain regions and the liver between young (8–9 months) and old (27–29 months) BN/BiRijHsd rats of both sexes.
Results: CAT activities in brain regions were quite comparable between young and old rats of both sexes. SOD activity changes with age also were not remarkable, with the exception of significantly lower Mn-SOD activities in substantia nigra and hippocampus of old male rats and significantly higher activities of Cu/Zn-SOD in substantia nigra of old female rats in comparison with respective values in young rats. CAT activities in the liver tended to be lower in old male rats, while in females the opposite was observed. SOD activities in the liver stayed essentially unchanged with age in males, while in females total as well as Cu/Zn-SOD activities were more than twofold higher in old animals.
Conclusion: These data coupled with previously reported results, indicate that no generalization can be made in terms of age-related changes in antioxidant enzyme activities. These differences emphasize the need of "public observations" in any attempt to generate a theory for mechanisms of aging based on antioxidant enzyme activity changes with age. 相似文献