A Study in Healthy Men to Test the Effects of Different Doses of BI 1467335 on MAO-B Activity in the Brain.

Aim and Objective: The Dendrobium officinalis flower (DOF) is popular in China due to common belief in its anti-aging properties and positive effects on “nourish yin”. However, there have been relatively few confirmatory pharmacological experiments conducted to date. The aim of this work was to evaluate whether DOF has beneficial effects on learning and memory in senescent rats, and, if so, to determine its potential mechanism of effect. Materials and Methods: SD rats were administrated orally DOF at a dose of 1.38, or 0.46 g/kg once a day for 8 weeks. Two other groups included a healthy untreated control group and a senescent control group. During the 7th week, a Morris water maze test was performed to assess learning and memory. At the end of the experiment, serum and brain samples were collected to measure concentrations of antioxidant enzymes, including malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GSH-Px) in serum, and the neurotransmitters, including γ-aminobutyric acid (γ-GABA), Glutamic (Glu), and monoamine oxidase B (MAO-B) in the brain. Histopathology of the hippocampus was assessed using hematoxylin-eosin (H&E) staining. Results: The results suggested that treatment with DOF improved learning as measured by escape latency, total distance, and target quadrant time, and also increased levels of γ-GABA in the brain. In addition, DOF decreased the levels of MDA, Glu, and MAO-B, and improved SOD and GSHPx. Histopathological analysis showed that DOF also significantly reduced structural lesions and neurodegeneration in the hippocampus relative to untreated senescent rats. Conclusion: DOF alleviated brain aging and improved the spatial learning abilities in senescent rats, potentially by attenuating oxidative stress and thus reducing hippocampal damage and balancing the release of neurotransmitters.

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Potential for imaging the high-affinity state of the 5-HT1B receptor: a comparison of three PET radioligands with differing intrinsic activity

EJNMMI Research ◽

10.1186/s13550-019-0570-1 ◽

2019 ◽

Vol 9 (1) ◽

Author(s):

Anton Lindberg ◽

Ryosuke Arakawa ◽

Tsuyoshi Nogami ◽

Sangram Nag ◽

Magnus Schou ◽

...

Keyword(s):

Pet Imaging ◽

Specific Binding ◽

Occipital Cortex ◽

Intrinsic Activity ◽

High Affinity ◽

G Protein Coupled ◽

Dose Dependent ◽

The Brain ◽

Agonist Affinity States ◽

Different Doses

Abstract Background Over the last decade, a few radioligands have been developed for PET imaging of brain 5-HT1B receptors. The 5-HT1B receptor is a G-protein-coupled receptor (GPCR) that exists in two different agonist affinity states. An agonist ligand is expected to be more sensitive towards competition from another agonist, such as endogenous 5-HT, than an antagonist ligand. It is of interest to know whether the intrinsic activity of a PET radioligand for the 5-HT1B receptor impacts on its ability to detect changes in endogenous synaptic 5-HT density. Three high-affinity 11C-labeled 5-HT1B PET radioligands with differing intrinsic activity were applied to PET measurements in cynomolgus monkey to evaluate their sensitivity to be displaced within the brain by endogenous 5-HT. For these experiments, fenfluramine was pre-administered at two different doses (1.0 and 5.0 mg/kg, i.v.) to induce synaptic 5-HT release. Results A dose-dependent response to fenfluramine was detected for all three radioligands. At the highest dose of fenfluramine (5.0 mg/kg, i.v.), reductions in specific binding in the occipital cortex increased with radioligand agonist efficacy, reaching 61% for [11C]3. The most antagonistic radioligand showed the lowest reduction in specific binding. Conclusions Three 5-HT1B PET radioligands were identified with differing intrinsic activity that could be used in imaging high- and low-affinity states of 5-HT1B receptors using PET. From this limited study, radioligand sensitivity to endogenous 5-HT appears to depend on agonist efficacy. More extensive studies are required to substantiate this suggestion.

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Effect of Propofol and Fentanyl on Brain Oxidative Stress after Systemic Lipopolysaccharide Injection in Rats

Reactive Oxygen Species ◽

10.20455/ros.2021.r.801 ◽

2021 ◽

Vol 11 ◽

Author(s):

Omar M.E. Abdel-Salam ◽

Eman R. Youness ◽

Nadia A. Mohammed ◽

Amr M.M. Ibrahim

Keyword(s):

Oxidative Stress ◽

Active Form ◽

Saline Group ◽

Paraoxonase 1 ◽

Stress Markers ◽

Anesthetic Agents ◽

Systemic Endotoxemia ◽

Brain Oxidative Stress ◽

The Brain ◽

Different Doses

Systemic inflammation causes brain oxidative stress, a prerequisite for neurodegeneration. In this study, we investigated the effect of the anesthetic agents propofol and fentanyl on brain oxidative stress during mild systemic endotoxemia induced by lipopolysaccharide (LPS) endotoxin. For this purpose, rats were administered LPS (400 μg/kg, intraperitoneally; i.p.), treated at the same time with different doses of propofol or fentanyl, i.p., and euthanized 4 h later. Other groups were treated with the saline, only propofol, or only fentanyl. Oxidative stress markers including malondialdehyde (MDA), nitric oxide (NO), and reduced glutathione (GSH) were determined. In addition, nuclear factor kappaB (NF-kB), paraoxonase-1 (PON-1), and butyrylcholinesterase (BChE) activities were measured in the brain tissue. Results showed that compared with the saline group, administration of LPS caused a marked and significant increase in brain MDA and NO combined with depletion of GSH and decreased PON-1 and BChE activities. Additionally, the active form of NF-kB was significantly increased in the brain of LPS only-treated rats. Treatment with propofol or fentanyl led to a marked and significant decrease in the levels of brain MDA and NO together with a significant increase in GSH and restoration of PON-1 and BChE activities. Furthermore, lower levels of active form of NF-kB were found following treatment with propofol or fentanyl compared with those in the LPS only group. Collectively, these results suggest that propofol and fentanyl exhibit an antioxidant action and attenuate the endotoxin-induced brain oxidative stress.

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Effect of Solanum macrocarpon Linn leaf aqueous extract on the brain of an alloxan-induced rat model of diabetes

Journal of International Medical Research ◽

10.1177/0300060520922649 ◽

2020 ◽

Vol 48 (6) ◽

pp. 030006052092264

Author(s):

Mary A. Okesola ◽

Basiru O. Ajiboye ◽

Babatunji E. Oyinloye ◽

Olukemi A. Osukoya ◽

Ofogho S. Owero-ozeze ◽

...

Keyword(s):

Aqueous Extract ◽

Rat Model ◽

Fasting Blood Glucose ◽

Diabetes Control ◽

Antioxidant Enzyme Activities ◽

Diabetes Group ◽

Leaf Aqueous Extract ◽

The Brain ◽

Different Doses ◽

Control Diabetes

Objective This study was designed to evaluate the protective effect of aqueous extract of Solanum macrocarpon Linn leaf in the brain of an alloxan-induced rat model of diabetes. Methods The experimental model of diabetes was induced by a single intraperitoneal injection of freshly prepared alloxan. Rats were then divided into six groups: normal control, diabetes control, diabetes group treated with metformin, and three diabetes groups treated with different concentrations of S. macrocarpon. Rats were sacrificed on day 14 of the experiment and different brain biochemical parameters were assessed and compared between groups. Results Administration of different doses of S. macrocarpon leaf aqueous extract was associated with significantly reduced levels of fasting blood glucose, lipid peroxidation, neurotransmitters, cholinesterases, cyclooxygenase-2 and nitric oxide compared with diabetes control rats. In addition, antioxidant enzyme activities were significantly increased in diabetes rats administered 12.45, 24.9 and 49.8 mg/kg body weight of S. macrocarpon versus diabetes control rats. Conclusion Aqueous extract of S. macrocarpon Linn leaf may be useful in the management of diabetic neuropathy.

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M211. NEUROPROTECTIVE EFFECT OF SHI-ZHEN-AN-SHEN-TANG, A CHINESE HERB FORMULA ON MICE EXPOSED TO CUPRIZONE

Schizophrenia Bulletin ◽

10.1093/schbul/sbaa030.523 ◽

2020 ◽

Vol 46 (Supplement_1) ◽

pp. S216-S217

Author(s):

Chao Ma ◽

Yan Wu ◽

Pei Chen ◽

Yuan Jia ◽

Dongqing Yin ◽

...

Keyword(s):

Low Dose ◽

Neuroprotective Effect ◽

Chinese Herb ◽

Large Body ◽

High Dose ◽

Neuregulin 1 ◽

The Brain ◽

Different Doses ◽

Medium Dose

Abstract Background Our previous study indicated a therapeutic effect of Shi-Zhen-An-Shen-Tang (SZAST), a Chinese herb formula, on schizophrenia, but the related mechanism is unknown(citation). A large body of evidence suggests the important role of white matter of the brain in the pathophysiology of schizophrenia. This study was designed to evaluate the effect of SZAST on schizophrenia with demyelinated mice. Methods Male C57BL/6 mice were given mixed cuprizone (CPZ, a copper chelator, 0.2 %, w/w) rodent chow for six successive weeks to induce demyelination. During the last two weeks, mice were given an oral gavage of saline, or SZAST of three different doses (a low dose of 5.5g·kg-1·d-1, a medium dose of 8.24g·kg-1·d-1, or a high dose of 10.98 g·kg-1·d-1), or quetiapine, respectively. Behavioral tests were conducted after the last treatment. Meanwhile, the expression of myelin basic protein (MBP) and neuregulin-1(NRG1) in the brain was tested by immunohistochemistry staining or Western Blot. Results Mice exposed to CPZ for six weeks showed obvious schizophrenia-like behaviors, including lower nest-building activity, sensory gating activity, and higher locomotor activity. CPZ-fed mice also displayed a lower myelin density in the corpus callosum, hippocampus, and cerebral cortex and a reduction of MBP and NRG1 protein in the hippocampus compared with controls. Both quetiapine and SZAST significantly alleviated the abnormal schizophrenia-like behaviors and the impairment of myelin sheath in CPZ-fed mice, however, SZAST with medium dose showed better neuroprotective effect than the low dose or the high dose of SZAST. Furthermore, the expression of NRG1protein in the hippocampus was slightly, but not significantly increased in all SZAST-treated and quetiapine-treated groups. Discussion These results indicate that the neuroprotective effect of SZAST in demyelinated mice might partially relate to remyelination in the hippocampus in CPZ-fed mice.

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Oxidative and DNA Damage Potential of Colemanite on Zebrafish: Brain, Liver and Blood

Turkish Journal of Fisheries and Aquatic Sciences ◽

10.4194/1303-2712-v20_8_02 ◽

2020 ◽

Vol 20 (8) ◽

pp. 593-602 ◽

Cited By ~ 3

Author(s):

Gonca Alak ◽

Veysel Parlak ◽

Arzu Ucar ◽

Aslı Cilingir Yeltekin ◽

Fatma Betul Ozgeris ◽

...

Keyword(s):

Dna Damage ◽

Boron Compounds ◽

Damage Potential ◽

Static Test ◽

Zebrafish Brain ◽

Commercially Important ◽

Animal Feeding ◽

The Brain ◽

Different Doses

Recently, boron has been used in animal feeding due to its significant biological roles. In this study, the action mechanism of colemanite (COL), a commercially important borate mineral, was aimed to investigate via evaluating parameters related to oxidative alterations on the brain, liver and blood tissues of zebrafish. For this purpose, zebrafish were exposed to different doses of COL (5, 10 and 20 mg/L) in a static test apparatus for 96 hours. Multiple biochemical analysis including determination of DNA damage (8-OHdG), apoptosis (Caspase-3), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), myeloperoxidase (MPO), paraoxonase (PON), arylesterase (AR) and lipid peroxidation (MDA) levels were performed in brain and liver tissues for assessing oxidative responses. In addition to micronucleus (MN) assay was performed in obtained blood tissues. The results indicated that low doses of COL supported antioxidant system and did not lead to oxidative stress in zebrafish brain and liver. Again, our results showed colemanite did not cause DNA damage or apoptosis at all tested concentrations. Besides the statistically insignificant changes (P>0.05) of MN rates of erythrocytes between the control and experimental groups revealed the non-genotoxic feature of COL on zebrafish. In conclusion, boron compounds especially COL can be used safely and provide positive impacts on aquatic environments.

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Phenethylamine is a substrate of monoamine oxidase B in the paraventricular thalamic nucleus

Scientific Reports ◽

10.1038/s41598-021-03885-6 ◽

2022 ◽

Vol 12 (1) ◽

Author(s):

Youhei Obata ◽

Mie Kubota-Sakashita ◽

Takaoki Kasahara ◽

Masafumi Mizuno ◽

Takahiro Nemoto ◽

...

Keyword(s):

Monoamine Oxidase ◽

Thalamic Nucleus ◽

Monoamine Oxidase B ◽

Tandem Mass ◽

Trace Amines ◽

Mao B ◽

Chromatography Tandem Mass Spectrometry ◽

Liquid Chromatography Tandem Mass ◽

Key Enzyme ◽

The Brain

AbstractMonoamine oxidase (MAO) is a key enzyme responsible for the degradation of neurotransmitters and trace amines. MAO has two subtypes (MAO-A and MAO-B) that are encoded by different genes. In the brain, MAO-B is highly expressed in the paraventricular thalamic nucleus (PVT); however, its substrate in PVT remains unclear. To identify the MAO-B substrate in PVT, we generated Maob knockout (KO) mice and measured five candidate substrates (i.e., noradrenaline, dopamine, 3-methoxytyramine, serotonin, and phenethylamine [PEA]) by liquid chromatography tandem mass spectrometry. We showed that only PEA levels were markedly elevated in the PVT of Maob KO mice. To exclude the influence of peripheral MAO-B deficiency, we developed brain-specific Maob KO mice, finding that PEA in the PVT was increased in brain-specific Maob KO mice, whereas the extent of PEA increase was less than that in global Maob KO mice. Given that plasma PEA levels were elevated in global KO mice, but not in brain–specific KO mice, and that PEA passes across the blood–brain barrier, the substantial accumulation of PEA in the PVT of Maob KO mice was likely due to the increase in plasma PEA. These data suggest that PEA is a substrate of MAO-B in the PVT as well as other tissues.

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Effect of Lepidium meyenii (Maca), a root with aphrodisiac and fertility-enhancing properties, on serum reproductive hormone levels in adult healthy men

Journal of Endocrinology ◽

10.1677/joe.0.1760163 ◽

2003 ◽

Vol 176 (1) ◽

pp. 163-168 ◽

Cited By ~ 88

Author(s):

GF Gonzales ◽

A Cordova ◽

K Vega ◽

A Chung ◽

A Villena ◽

...

Keyword(s):

Serum Testosterone ◽

Serum Levels ◽

Reproductive Hormone ◽

Double Blind ◽

Healthy Men ◽

Hormone Levels ◽

Lepidium Meyenii ◽

The Times ◽

Changes Over Time ◽

Different Doses

Lepidium meyenii (Maca) is a Peruvian hypocotyl that grows exclusively between 4000 and 4500 m in the central Andes. Maca is traditionally employed in the Andean region for its supposed aphrodisiac and/or fertility-enhancing properties. This study was a 12-week double-blind, placebo-controlled, randomized, parallel trial in which active treatment with different doses of Maca Gelatinizada was compared with a placebo. The study aimed to test the hypothesis that Maca has no effect on serum reproductive hormone levels in apparently healthy men when administered in doses used for aphrodisiac and/or fertility-enhancing properties. Men aged between 21 and 56 Years received 1500 mg or 3000 mg Maca. Serum levels of luteinizing hormone, follicle-stimulating hormone, prolactin, 17-alpha hydroxyprogesterone, testosterone and 17-beta estradiol were measured before and at 2, 4, 8 and 12 weeks of treatment with placebo or Maca (1.5 g or 3.0 g per day). Data showed that compared with placebo Maca had no effect on any of the hormones studied nor did the hormones show any changes over time. Multiple regression analysis showed that serum testosterone levels were not affected by treatment with Maca at any of the times studied (P, not significant). In conclusion, treatment with Maca does not affect serum reproductive hormone levels.

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