Myriocin, a serine palmitoyltransferase inhibitor, alters regional brain neurotransmitter levels without concurrent inhibition of the brain sphingolipid biosynthesis in mice

2004 ◽  
Vol 147 (1) ◽  
pp. 87-94 ◽  
Author(s):  
Marcin F. Osuchowski ◽  
Victor J. Johnson ◽  
Quanren He ◽  
Raghubir P. Sharma
Keyword(s):  
Serine Palmitoyltransferase ◽  
Regional Brain ◽  
Brain Neurotransmitter ◽  
Sphingolipid Biosynthesis ◽  
The Brain

scholarly journals High-fat diet-induced obesity and impairment of brain neurotransmitter pool

2020 ◽  
Vol 11 (1) ◽  
pp. 147-160
Author(s):  
Ranyah Shaker M. Labban ◽  
Hanan Alfawaz ◽  
Ahmed T. Almnaizel ◽  
Wail M. Hassan ◽  
Ramesa Shafi Bhat ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Brain Tissue ◽  
High Fat Diet ◽  
Density Lipoprotein ◽  
Obese Group ◽  
Control Group ◽  
High Fat ◽  
Brain Neurotransmitter ◽  
The Brain ◽  
Lean Group

AbstractObesity and the brain are linked since the brain can control the weight of the body through its neurotransmitters. The aim of the present study was to investigate the effect of high-fat diet (HFD)-induced obesity on brain functioning through the measurement of brain glutamate, dopamine, and serotonin metabolic pools. In the present study, two groups of rats served as subjects. Group 1 was fed a normal diet and named as the lean group. Group 2 was fed an HFD for 4 weeks and named as the obese group. Markers of oxidative stress (malondialdehyde, glutathione, glutathione-s-transferase, and vitamin C), inflammatory cytokines (interleukin [IL]-6 and IL-12), and leptin along with a lipid profile (cholesterol, triglycerides, high-density lipoprotein, and low-density lipoprotein levels) were measured in the serum. Neurotransmitters dopamine, serotonin, and glutamate were measured in brain tissue. Fecal samples were collected for observing changes in gut flora. In brain tissue, significantly high levels of dopamine and glutamate as well as significantly low levels of serotonin were found in the obese group compared to those in the lean group (P > 0.001) and were discussed in relation to the biochemical profile in the serum. It was also noted that the HFD affected bacterial gut composition in comparison to the control group with gram-positive cocci dominance in the control group compared to obese. The results of the present study confirm that obesity is linked to inflammation, oxidative stress, dyslipidemic processes, and altered brain neurotransmitter levels that can cause obesity-related neuropsychiatric complications.

scholarly journals Housing and road transport modify the brain neurotransmitter systems of pigs: Do pigs raised in different conditions cope differently with unknown environments?

PLoS ONE ◽  
2019 ◽  
Vol 14 (1) ◽  
pp. e0210406 ◽  
Author(s):  
Laura Arroyo ◽  
Daniel Valent ◽  
Ricard Carreras ◽  
Raquel Peña ◽  
Josefa Sabrià ◽  
...  
Keyword(s):  
Road Transport ◽  
Neurotransmitter Systems ◽  
Unknown Environments ◽  
Brain Neurotransmitter ◽  
The Brain

Brain glucose metabolism in hypobaric hypoxia

1995 ◽  
Vol 79 (1) ◽  
pp. 136-140 ◽  
Author(s):  
S. I. Harik ◽  
W. D. Lust ◽  
S. C. Jones ◽  
K. L. Lauro ◽  
S. Pundik ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Atmospheric Pressure ◽  
Hypobaric Hypoxia ◽  
Capillary Density ◽  
Brain Capillary ◽  
Brain Glucose ◽  
Adult Rat ◽  
Brain Microvessels ◽  
Regional Brain ◽  
The Brain

Hypobaric hypoxia at one-half atmospheric pressure for 3 wk was reported to increase the brain capillary density and glucose transport at the blood-brain barrier in the adult rat. We examined the metabolic concomitants of these alterations in rats subjected to the same hypoxic insult. Hypoxic rats increased brain glucose and lactate concentrations and decreased brain glycogen. However, hypoxia had no significant effects on regional brain levels of ATP and phosphocreatine or on intracellular pH, indicating successful adaptation to the hypoxic insult. 2-Deoxyglucose studies showed that hypoxia increased the regional metabolic rate for glucose by 10–40%. These results indicate increased glycolysis in the hypoxic rat brain, which probably underlies the increased density of glucose transporters in brain microvessels and the increased blood-to-brain glucose influx in hypoxia.

scholarly journals Characterization of an Arabidopsis cDNA Encoding a Subunit of Serine Palmitoyltransferase, the Initial Enzyme in Sphingolipid Biosynthesis

2001 ◽  
Vol 42 (11) ◽  
pp. 1274-1281 ◽  
Author(s):  
Kentaro Tamura ◽  
Naoto Mitsuhashi ◽  
Ikuko Hara-Nishimura ◽  
Hiroyuki Imai
Keyword(s):  
Serine Palmitoyltransferase ◽  
A Subunit ◽  
Sphingolipid Biosynthesis

Regulation of de novo sphingolipid biosynthesis and the toxic consequences of its disruption

2001 ◽  
Vol 29 (6) ◽  
pp. 831-835 ◽  
Author(s):  
S. C. Linn ◽  
H. S. Kim ◽  
E. M. Keane ◽  
L. M. Andras ◽  
E. Wang ◽  
...  
Keyword(s):  
De Novo ◽  
Uv Light ◽  
Wide Spectrum ◽  
Sphingolipid Metabolism ◽  
Intrinsic Activity ◽  
Type I ◽  
Serine Palmitoyltransferase ◽  
Post Translational Modification ◽  
Sphingolipid Biosynthesis ◽  
Complex Sphingolipids

Complex sphingolipids are ‘built’ on highly bio-active backbones (sphingoid bases and ceramides) that can cause cell death when the amounts are elevated by turnover of complex sphingolipids, disruption of normal sphingolipid metabolism, or over-induction of sphingolipid biosynthesis de novo. Under normal conditions, it appears that the bioactive intermediates of this pathway (3-keto-sphinganine, sphinganine and ceramides) are kept at relatively low levels. Both the intrinsic activity of serine palmitoyltransferase (SPT) and the availability of its substrates (especially palmitoyl-CoA) can have toxic consequences for cells by increasing the production of cytotoxic intermediates. Recent work has also revealed that diverse agonists and stresses (cytokines, UV light, glucocorticoids, heat shock and toxic compounds) modulate SPT activity by induction of SPTLC2 gene transcription and/or post-translational modification. Mutation of the SPTLC1 component of SPT has also been shown to cause hereditary sensory neuropathy type I, possibly via aberrant oversynthesis of sphingolipids. Another key step of the pathway is the acylation of sphinganine (and sphingosine in the recycling pathway) by ceramide synthase, and up-regulation of this enzyme (or its inhibition to cause accumulation of sphinganine) can also be toxic for cells. Since it appears that most, if not all, tissues synthesize sphingolipids de novo, it may not be surprising that disruption of this pathway has been implicated in a wide spectrum of disease.

scholarly journals Exploring the Multi-Target Performance of Mitochondriotropic Antioxidants against the Pivotal Alzheimer’s Disease Pathophysiological Hallmarks

Molecules ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 276 ◽  
Author(s):  
Sofia Benfeito ◽  
Carlos Fernandes ◽  
Santiago Vilar ◽  
Fernando Remião ◽  
Eugenio Uriarte ◽  
...  
Keyword(s):  
Protein Misfolding ◽  
Neuronal Damage ◽  
Memory Loss ◽  
Carbon Chain ◽  
New Chemical Entities ◽  
Brain Neurotransmitter ◽  
Β Amyloid ◽  
Target Performance ◽  
Protein Misfolding And Aggregation ◽  
The Brain

Alzheimer disease (AD) is the most common neurodegenerative disease featuring progressive and degenerative neurological impairments resulting in memory loss and cognitive decline. The specific mechanisms underlying AD are still poorly understood, but it is suggested that a deficiency in the brain neurotransmitter acetylcholine, the deposition of insoluble aggregates of fibrillar β-amyloid 1–42 (Aβ42), and iron and glutamate accumulation play an important role in the disease progress. Despite the existence of approved cholinergic drugs, none of them demonstrated effectiveness in modifying disease progression. Accordingly, the development of new chemical entities acting on more than one target is attracting progressively more attention as they can tackle intricate network targets and modulate their effects. Within this endeavor, a series of mitochondriotropic antioxidants inspired on hydroxycinnamic (HCA’s) scaffold were synthesized, screened toward cholinesterases and evaluated as neuroprotectors in a differentiated human SH-SY5Y cell line. From the series, compounds 7 and 11 with a 10-carbon chain can be viewed as multi-target leads for the treatment of AD, as they act as dual and bifunctional cholinesterase inhibitors and prevent the neuronal damage caused by diverse aggressors related to protein misfolding and aggregation, iron accumulation and excitotoxicity.

Nonuniform brain blood flow response to hypoxia in unanesthetized cats

1984 ◽  
Vol 57 (6) ◽  
pp. 1803-1808 ◽  
Author(s):  
J. A. Neubauer ◽  
N. H. Edelman
Keyword(s):  
Blood Flow ◽  
Brain Stem ◽  
Sympathetic Innervation ◽  
Brain Blood Flow ◽  
Intact Side ◽  
Flow Response ◽  
Regional Brain ◽  
Sympathetic Nervous ◽  
The Brain ◽  
Increased Blood Flow

In seven unanesthetized cats, radiolabeled microspheres were used to determine regional brain blood flow (rBBF) to the medulla-pons (M-P), midbrain-thalamus (M-T), cerebellum (Cb), and cortex (Cx) during three conditions: 1) control [arterial O2 tension (PaO2) = 81 Torr, arterial CO2 tension (PaCO2) = 26 Torr]; 2) hypocapnic hypoxia (PaO2 = 39 Torr, PaCO2 = 22 Torr); and 3) isocapnic hypoxia (PaO2 = 47 Torr, PaCO2 = 26 Torr). Hypoxia increased blood flow significantly more in the caudal brain stem (M-P) than in the Cx (P less than 0.05) during both hypocapnic hypoxia (M-P/Cx: +33/ +17 ml X min-1 X 100 g-1) and isocapnic hypoxia (M-P/Cx: +13/ -2 ml X min-1 X 100 g-1). Since sympathetic innervation is greater anatomically to rostral than to caudal vessels, we examined the rBBF response to hypocapnic hypoxia in seven additional cats after unilateral superior cervical gangliectomy. All seven cats had a reduction in the cortical-to-caudal brain stem trend on the denervated side of the brain (M-P/Cx: +27/+28 ml X min-1 X 100 g-1) compared with the intact side of the brain (M-P/Cx: +34/+24 ml X min-1 X 100 g-1) owing to both increases in Cx and decreases in M-P flows. We conclude that in unanesthetized cats hypoxia causes a greater increase in the caudal brain stem compared with cortical blood flow, and this differential response is related to modulation by the sympathetic nervous system.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals ORMDL/serine palmitoyltransferase stoichiometry determines effects of ORMDL3 expression on sphingolipid biosynthesis

2015 ◽  
Vol 56 (4) ◽  
pp. 898-908 ◽  
Author(s):  
Deanna Siow ◽  
Manjula Sunkara ◽  
Teresa M. Dunn ◽  
Andrew J. Morris ◽  
Binks Wattenberg
Keyword(s):  
Serine Palmitoyltransferase ◽  
Sphingolipid Biosynthesis

Fluorescent signalling of the brain neurotransmitter γ-aminobutyric acid and related amino acid zwitterions

1996 ◽  
pp. 2191-2192 ◽  
Author(s):  
A. Prasanna de Silva ◽  
H. Q. Nimal Gunaratne ◽  
Catherine McVeigh ◽  
Glenn E. M. Maguire ◽  
Pamela R. S. Maxwell ◽  
...  
Keyword(s):  
Amino Acid ◽  
Aminobutyric Acid ◽  
Brain Neurotransmitter ◽  
The Brain ◽  
Related Amino Acid

scholarly journals Crassaostrea gigas Oyster Shell Extract Inhibits Lipogenesis via Suppression of Serine Palmitoyltransferase

2015 ◽  
Vol 10 (2) ◽  
pp. 1934578X1501000
Author(s):  
Nguyen Khoi Song Tran ◽  
Jeong Eun Kwon ◽  
Se Chan Kang ◽  
Soon-Mi Shim ◽  
Tae-Sik Park
Keyword(s):  
De Novo ◽  
Preventive Measure ◽  
Ethanol Extract ◽  
Oyster Shell ◽  
Lipid Lowering ◽  
Metabolic Dysfunction ◽  
Serine Palmitoyltransferase ◽  
Lipogenic Gene Expression ◽  
Cholesterol Levels ◽  
Sphingolipid Biosynthesis

Oysters are widely consumed seafood, but their shells impose a serious environmental problem. To extend the utilization of oyster shell waste, we investigated the biological role of oyster shell extract. In this study, we verified that the ethanol extract of oyster shell (EOS) contains taurine and betaine, the major components of oyster body. EOS downregulated transcription of Sptlc1 and Sptlc2 mRNA, the subunits of serine palmitoyltransferase (SPT). Suppression of SPT subunits reduced sphinganine and sphingomyelin by inhibiting de novo sphingolipid biosynthesis. Inhibition of sphingomyelin biosynthesis resulted in downregulation of lipogenic gene expression such as ACC, FAS, SCD1, and DGAT2. Consistent with inhibition of lipogenesis, cellular triglyceride levels were diminished by EOS, but cholesterol levels were not altered. Taken together, these results suggest that EOS has a lipid-lowering effect and could be applied as either a therapeutic or preventive measure for metabolic dysfunction.

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