1.Advances in basic research on choline and central nervous system development and related disorders.
Zheng Long XIA ; Xu Ying TAN ; Yan Yan SONG
Chinese Journal of Preventive Medicine 2023;57(5):793-800
Choline is an essential nutrient that plays an integral role in all stages of the life cycle, with increasing interest in the relationship between choline and neurodevelopment. Choline is a major component in the synthesis of phospholipids, phosphatidylcholine and sphingolipids, and is an essential nutrient for methyl metabolism, acetylcholine synthesis and cell signaling. Choline plays an important role in neurogenesis and neural migration during fetal development, potentially influencing the development and prognosis of neurological disorders, but its mechanism of action is not yet clear. This article reviews the source and metabolism of choline, the effects and mechanism of choline on neurodevelopment and central nervous system related disorders.
Humans
;
Choline/metabolism*
;
Phosphatidylcholines/metabolism*
;
Central Nervous System/metabolism*
2.Expression of choline acetyltransferase in the rat barrel cortex by electrical stimulation.
Hong-Kun FAN ; Chun YANG ; Yan-Yan ZHANG ; Xiao-Ping LE ; Chun-Guang ZHENG ; Li SHI ; Qian ZHANG
Chinese Journal of Applied Physiology 2013;29(4):312-316
OBJECTIVETo observe a turning performance in the rats excited by using a proper electrical stimuli of the barrel cortex region (BC), and the expression of choline acetyltransferase (ChAT) in the BC regions after electoral stimulation.
METHODSSD rats were divided into three groups. The stimulation electrodes were surgically implanted into the bilateral BC regions in the control group and the experimental group rats. The experiment group post surgery for seven days was given the electrical impulses via connection with the electrodes for three times each day through consecutive three days. Three groups of the rats were killed and the brains were quickly removed for frozen sections and then performed with conventional HE and immunohistochemistry staining. And protein samples were prepared from brain and the hippocampus tissues of the three groups to detect the level of the ChAT protein by Western blot.
RESULTSThe experimental rats turn left or right when continuously stimulation in the bilateral BC regions with electric pulse. HE staining showed no significant damage around electrodes in the cerebral cortex. Compared with the control and blank groups, the ChAT positive rate in the brain section in the experimental rats was significantly high by immunohistochemistry assay; the level of the ChAT protein in the rats given the electrical stimulation increased.
CONCLUSIONTurnings performance of the rat could be initiated hy electrical stimuli in the BC region. Expression of ChAT is significantly higher in the BC regions of rat under electrical stimulation, suggesting that acetylcholine might be associated with signal transmission between senses and movement behavior in the nervous central system.
Acetylcholine ; metabolism ; Animals ; Cerebral Cortex ; metabolism ; Choline O-Acetyltransferase ; metabolism ; Electric Stimulation ; Rats ; Rats, Sprague-Dawley
3.FMO3-TMAO axis modulates the clinical outcome in chronic heart-failure patients with reduced ejection fraction: evidence from an Asian population.
Haoran WEI ; Mingming ZHAO ; Man HUANG ; Chenze LI ; Jianing GAO ; Ting YU ; Qi ZHANG ; Xiaoqing SHEN ; Liang JI ; Li NI ; Chunxia ZHAO ; Zeneng WANG ; Erdan DONG ; Lemin ZHENG ; Dao Wen WANG
Frontiers of Medicine 2022;16(2):295-305
The association among plasma trimethylamine-N-oxide (TMAO), FMO3 polymorphisms, and chronic heart failure (CHF) remains to be elucidated. TMAO is a microbiota-dependent metabolite from dietary choline and carnitine. A prospective study was performed including 955 consecutively diagnosed CHF patients with reduced ejection fraction, with the longest follow-up of 7 years. The concentrations of plasma TMAO and its precursors, namely, choline and carnitine, were determined by liquid chromatography-mass spectrometry, and the FMO3 E158K polymorphisms (rs2266782) were genotyped. The top tertile of plasma TMAO was associated with a significant increment in hazard ratio (HR) for the composite outcome of cardiovascular death or heart transplantation (HR = 1.47, 95% CI = 1.13-1.91, P = 0.004) compared with the lowest tertile. After adjustments of the potential confounders, higher TMAO could still be used to predict the risk of the primary endpoint (adjusted HR = 1.33, 95% CI = 1.01-1.74, P = 0.039). This result was also obtained after further adjustment for carnitine (adjusted HR = 1.33, 95% CI = 1.01-1.74, P = 0.039). The FMO3 rs2266782 polymorphism was associated with the plasma TMAO concentrations in our cohort, and lower TMAO levels were found in the AA-genotype. Thus, higher plasma TMAO levels indicated increased risk of the composite outcome of cardiovascular death or heart transplantation independent of potential confounders, and the FMO3 AA-genotype in rs2266782 was related to lower plasma TMAO levels.
Carnitine
;
Choline/metabolism*
;
Chronic Disease
;
Heart Failure/genetics*
;
Humans
;
Methylamines
;
Oxygenases
;
Prospective Studies
4.The metabolic changes of mice serum after loaded swimming.
Jian-Quan WU ; Chang-Jiang GUO ; Wei-Na GAO ; Jin LIU ; Jing-Yu WELI ; Ji-Jun YANG
Chinese Journal of Applied Physiology 2011;27(1):42-45
OBJECTIVETo investigate the metabolic changes of mice serum after loaded swimming and to provide a basis for the study of anti-fatigue functional food.
METHODSThe male Kunming mice were randomly divided into four group, fed an AIN-93 diet for 14 days, and forced to swim for 30, 60 or 120 min, respectively, with a load on their tails. The mice were executed after swimming immediately and the changes of serum metabolic profiles were analyzed using metabolomic approach. The spectrum was acquired by using Carr Purcell Meiboom Gill (CPMG) or Longitudinal Eddy Current Delay (LED) sequence, and transformed into 1H NMR spectrogram via Fourier transformation. All the data were analyzed by principal component analysis by using the SIMCA-P+ software.
RESULTSThe serum metabolic profiles changed significantly after loaded swimming. Serum beta-hydroxybutyric acid, acetate, lactate, lipid were increased and glucose, choline, phosphorylcholine, alanine and phosphatidylcholine decreased. These changes were time dependent.
CONCLUSIONThe changes of serum metabolic profiles after loaded swimming were time dependent, especially for lipid metabolite.Further study based on the interaction of choline and lipid metabolism may contribute to understand the mechanism of fatigue.
Animals ; Choline ; metabolism ; Fatigue ; blood ; metabolism ; physiopathology ; Lipid Metabolism ; Male ; Metabolome ; Mice ; Physical Exertion ; physiology ; Swimming ; physiology
5.Proton magnetic resonance spectroscopy of normal human brain and glioma: a quantitative in vivo study.
Zhi-yong TONG ; Yamaki TOSHIAKI ; Yun-jie WANG
Chinese Medical Journal 2005;118(15):1251-1257
BACKGROUNDIn vivo proton magnetic resonance spectroscopy (MRS) provides a noninvasive method of examining a wide variety of cerebral metabolites in both healthy subjects and patients with various brain diseases. Absolute metabolite concentrations have been determined using external and internal standards with known concentrations. When an external standard is placed beside the head, variations in signal amplitudes due to B1 field inhomogeneity and static field inhomogeneity may occur. Hence an internal standard is preferable. The purpose of this study was to quantitatively analyze the metabolite concentrations in normal adult brains and gliomas by in vivo proton MRS using the fully relaxed water signal as an internal standard.
METHODSBetween January 1998 and October 2001, 28 healthy volunteers and 16 patients with gliomas were examined by in vivo proton MRS. Single-voxel spectra were acquired using the point-resolved spectroscopic pulse sequence with a 1.5 T scanner (TR/TE/Ave = 3000 ms/30 ms/64).
RESULTSThe calculated concentrations of N-acetyl-asparatate (NAA), creatine (Cre), choline (Cho), and water (H2O) in the normal hemispheric white matter were (23.59 +/- 2.62) mmol/L, (13.06 +/- 1.8) mmol/L, (4.28 +/- 0.8) mmol/L, and (47,280.96 +/- 5414.85) mmol/L, respectively. The metabolite concentrations were not necessarily uniform in different parts of the brain. The concentrations of NAA and Cre decreased in all gliomas (P < 0.001). The ratios of NAA/Cho and NAA/H2O showed a significant difference between the normal brain and gliomas, and also between the high and low grades (P < 0.001).
CONCLUSIONSQuantitative analysis of in vivo proton MR spectra using the fully relaxed water signal as an internal standard is useful. The concentrations of NAA and the ratios of NAA/H2O and NAA/Cho conduce to discriminating between the glioma and normal brain, and also between the low-grade glioma and high-grade glioma.
Adult ; Aspartic Acid ; analogs & derivatives ; metabolism ; Brain ; metabolism ; Choline ; metabolism ; Creatine ; metabolism ; Female ; Glioma ; metabolism ; Glycine ; metabolism ; Humans ; Inositol ; metabolism ; Magnetic Resonance Spectroscopy ; Male
6.Initial Experiences with Proton MR Spectroscopy in Treatment Monitoring of Mitochondrial Encephalopathy.
Seung Koo LEE ; Jinna KIM ; Heung Dong KIM ; Joon Soo LEE ; Young Mock LEE
Yonsei Medical Journal 2010;51(5):672-675
PURPOSE: Mitochondrial encephalopathy (ME) is a rare disorder of energy metabolism. The disease course can roughly be evaluated by clinical findings. The purpose of this study was to evaluate metabolic spectral changes using proton MR spectroscopy (MRS), and to establish a way to monitor ME by neuroimaging. MATERIALS AND METHODS: Proton MRS data were retrospectively reviewed in 12 patients with muscle biopsy-confirmed ME (M : F = 7 : 5, Mean age = 4.8 years). All received 1H-MRS initially and also after a ketogenic diet and mitochondrial disease treatment cocktail (follow up average was 10.2 months). Changes of N-acetylaspartate/creatine (NAA/Cr) ratio, choline/creatine (Cho/Cr) ratio, and lactate peak in basal ganglia at 1.2 ppm were evaluated before and after treatment. Findings on conventional T2 weighted MR images were also evaluated. RESULTS: On conventional MRI, increased basal ganglia T2 signal intensity was the most common finding with ME (n = 9, 75%), followed by diffuse cerebral atrophy (n = 8, 67%), T2 hyperintense lesions at pons and midbrain (n = 4, 33%), and brain atrophy (n = 2, 17%). Lactate peak was found in 4 patients; 2 had disappearance of the peak on follow up MRS. Quantitative analysis showed relative decrease of Cho/Cr ratio on follow up MRS (p = 0.0058, paired t-test, two-tailed). There was no significant change in NAA/Cr ratio. CONCLUSION: MRS is a useful tool for monitoring disease progression or impro-vement in ME, and decrease or disappearance of lactate peak and reduction of Cho/Cr fraction were correlated well with improvement of clinical symptoms.
Adolescent
;
Child
;
Child, Preschool
;
Choline/metabolism
;
Creatine/metabolism
;
Female
;
Humans
;
Infant
;
*Magnetic Resonance Spectroscopy
;
Male
;
Mitochondrial Encephalomyopathies/*pathology
;
Retrospective Studies
7.Effects of echinacoside on extracellular acetylcholine and choline levels of hippocampus and striatum of cerebral ischemia rats.
Chun-Li LIU ; Hong CHEN ; Yong JIANG ; Peng-Fei TU ; Ming ZHONG ; Jing-Yi MA ; Hui DING ; Wan-Xin ZHANG ; Xiao-Min JIN
Acta Pharmaceutica Sinica 2013;48(5):790-793
The aim of this study is to investigate the effect of echinacoside (ECH) on cholinergic neurotransmitter extracellular of hippocampus and striatum and its possible mechanisms of neuro-protective effect against vascular dementia rats. In this study brain microdialysis technique combined with HPLC-IMER-ECD (high-performance liquid chromatography-immobilized enzyme reactor-electrochemical detector) was used. The bilateral common carotid arteries occluded in two times operation at 72 h interval for vascular dementia model rats were used and the successful vascular dementia model rats were examined by Morris water maze. The content of acetylcholine (ACh) and choline (Ch) of microdialysate extracellular of hippocampus and striatum was determined by HPLC-IMER-ECD and the AChE activity in the hippocampus was measured. The results showed that the success rate of vascular dementia model was 83.08% after six weeks; the results also showed that echinacoside and galantamine could increase the content of ACh and reduce the content of Ch extracellular of hippocampus and striatum significantly and the AChE activity increased significantly compared with that of the model group. The results suggested that echinacoside could promote the recovery of cholinergic neurotransmitter levels in vascular dementia rats' brain, which may be one of the mechanisms of neuro-protection.
Acetylcholine
;
metabolism
;
Animals
;
Choline
;
metabolism
;
Corpus Striatum
;
metabolism
;
Dementia, Vascular
;
metabolism
;
Glycosides
;
pharmacology
;
Hippocampus
;
metabolism
;
Male
;
Neuroprotective Agents
;
pharmacology
;
Random Allocation
;
Rats
;
Rats, Sprague-Dawley
8.1H-proton magnetic resonance spectroscopy in patients with multiple system atrophy and cognitive dysfunction.
Xiaoshuang XIANG ; Xuan HOU ; Zhanfang SUN ; Gaofeng ZHOU ; Beisha TANG ; Hong JIANG
Journal of Central South University(Medical Sciences) 2015;40(6):639-645
OBJECTIVE:
To detect metabolic changes of bilateral frontal lobe in patients with multiple system atrophy (MSA) and cognitive dysfunction by 1H-proton magnetic resonance spectroscopy (1H-MRS).
METHODS:
N-acetylaspartate (NAA)/creatine(Cr), choline (Cho)/Cr, myoinositol (mI)/Cr in three sides of frontal lobe were detected by 1H-MRS in 48 healthy controls, 23 patients with MSA and cognitive dysfunction and 19 patients with MSA but without cognitive dysfunction.
RESULTS:
NAA/Cr of bilateral frontal lobes in patients with MSA and cognitive dysfunction was significantly decreased compared with MSA patients without cognitive dysfunction and healthy controls (P<0.05). mI/Cr of right frontal lobes was significantly increased in patients with MSA and cognitive dysfunction compared with healthy controls (P<0.05). There was a negative correlation between NAA/Cr of bilateral frontal lobes and duration while a positive correlation between NAA/Cr of bilateral frontal lobes and MoCA score in patients with MSA and cognitive dysfunction.
CONCLUSION
There is a decrease in NAA/Cr and an increase in mI/Cr in frontal lobes in patients with MSA and cognitive dysfunction, which may be associated with cognitive dysfunction in MSA patients.
Aspartic Acid
;
analogs & derivatives
;
metabolism
;
Choline
;
metabolism
;
Cognition Disorders
;
physiopathology
;
Creatine
;
metabolism
;
Frontal Lobe
;
metabolism
;
Humans
;
Inositol
;
metabolism
;
Multiple System Atrophy
;
physiopathology
;
Proton Magnetic Resonance Spectroscopy
9.Change of memory function and decrease of nitric oxide level of whole brain in the transgenic mice expressing human tau 40 with P301L mutation.
Ig-wei GAO ; Li-xia YU ; Yan HONG ; Chao NIU ; Yuan CHEN ; Xue-lan WANG ; Ru-zhu CHEN ; Wang HAI
Chinese Journal of Applied Physiology 2015;31(5):385-389
OBJECTIVETo study the mechanism of learning and memory dysfuction in the transgenic mouse expressing human tau 40 isoform with P301L mutation (F10).
METHODSThe human tau protein expression and phosphor-tau protein levels were detected with Western blot method. The neurofibrillary tangles were observed with Bielshowsky silver stain. The behavior changes of learning and memory were observed by open field test and passive avoidance test. Acetyleholine level, activities of acetycholinesterase and choline acetyltransferase of whole brain was detected by colorimetry method. The nitric oxide level of whole brain was detected by nitrate enzyme reduction method.
RESULTSExogenous human tau gene was expressed and an elevation of phosphor-tau protein level in 7 and 3-month transgenic mice's hippocampus andcerebrocortex was observed. The neurofibrillary tangles were observed in cerebrocortex of 7-month transgenic mice; the 7-month transgenic mice also presented an evident reduction of learning and memory ability and nitric oxide level of the whole brain, but not changes in acetylcholine level, acetycholinesterase activity, choline acetyltransferase activity and expression in whole brain.
CONCLUSIONTau transgenic mice (F10) can still inherit their parents' biologiccal characters, and develop learning and memory dysfunction awnodh san obvious decrease in nitric oxide level of whole brain in the 7-month old mice, suggesting a decrease of nitric oxide level of whole brain would be involved in the mechanism of learning and memory dysfunction in these transgenic mice.
Acetylcholine ; metabolism ; Acetylcholinesterase ; metabolism ; Animals ; Brain ; physiopathology ; Choline O-Acetyltransferase ; metabolism ; Humans ; Membrane Proteins ; genetics ; Memory Disorders ; genetics ; physiopathology ; Mice ; Mice, Transgenic ; Mutation ; Nitric Oxide ; metabolism
10.Evaluation of cerebral vasospasm resulting from subarachnoid hemorrhage with 1H-magnetic resonance spectroscopy.
Wei QUAN ; Tie-lin LI ; Guang-zhong CHEN ; Xiao-dan JIANG ; Ru-xiang XU ; Yi-quan KE ; Chuan-zhi DUAN ; Jian-ping LÜ ; Hao ZHANG ; Wei XIE ; Wen-jun ZHONG ; Ying-dong CHEN ; Fan-fan CHEN
Journal of Southern Medical University 2006;26(3):352-354
OBJECTIVETo assess the value of (1)H-magnetic resonance spectroscopy ((1)H-MRS) in evaluating cerebral vasospasm resulting from subarachnoid hemorrhage (SAH).
METHODSSix dogs were subjected to autologous non-heparinized blood injection via cisternal puncture twice at one-day interval to establish models of SAH, and another 6 received injections with normal saline in an identical manner. (1)H-MRS scan was performed on the 3rd, 7th and 14th days after the injections to measure the changes of N-acetylaspartate (NAA), creatine (Cr) and choline (Cho). After the (1)H-MRS scan, all the dogs underwent brain digital subtraction angiography (DSA) for determining the basilar artery diameter.
RESULTSDSA results on day 3 presented development of obvious vasospasm of the basilar artery, which was most evident on day 7 and recovered obviously on day 14. (1)H-MRS results demonstrated obvious changes of NAA, Cho and Cr on days 3 and 7 in SAH model group, and NAA declined to the lowest level on day 3 followed by gradual ascending till reaching the normal level on day 14. Cho decreased slightly on day 3, then increased and reached the peak level on day 7 and then decreased. Cr rose steadily from day 3 to 14, but since day 7, the rise slowed down obviously and Cr maintain a level not significantly different from that on day 14 (P>0.05). The functional results of (1)H-MRS were consistent with the DSA results.
CONCLUSION(1)H-MRS can be used to monitor the development of cerebral vasospasm resulting from SAH as a good evaluation method for functional imaging.
Animals ; Aspartic Acid ; analogs & derivatives ; metabolism ; Choline ; metabolism ; Creatine ; metabolism ; Dogs ; Female ; Magnetic Resonance Spectroscopy ; methods ; Male ; Protons ; Subarachnoid Hemorrhage ; complications ; Time Factors ; Vasospasm, Intracranial ; diagnosis ; etiology ; metabolism