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      Multi-organ assessment via a 9.4-Tesla MRS evaluation of metabolites during the embryonic development of cleft palate induced by dexamethasone

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          Abstract

          The aim of the present study was to determine the association between maternal metabolism and development of the fetal palate, and to suggest a potential non-invasive prenatal diagnostic method for fetal cleft palate (CP). Dexamethasone (DXM) was used to create a CP mouse model. A 9.4-Tesla (T) magnetic resonance spectroscopy (MRS) imager was used to measure an array of metabolites in the maternal serum, placental tissue, amniotic fluid and fetal palates. Multivariate statistical analysis was performed using SIMCA-P 14.1 software. Following DXM treatment, variations were detected in multiple metabolites in the female mice and their fetuses based on 9.4T MRS. It was indicated that in the experimental group during CP formation, leucine, valine, creatine, acetate and citrate levels in the palatal tissue were lower, whereas lactate, alanine, proline/inositol and glutamate-containing metabolite levels were higher, compared with the levels in the control group. In placental tissue and amniotic fluid, succinate and choline levels were lower in the experimental group. The relative concentrations of cholesterol and lipids in palatal tissues from mice treated with DXM were higher compared with the concentrations in tissues from mice in the control group, with the exception of (CH 2)n lipids. In the placental tissue, the alteration in cholesterol level exhibited the opposite trend. Lipid levels for the different lipid forms varied and most of them were unsaturated lipids.

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          Most cited references45

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          Glutamate as a neurotransmitter in the brain: review of physiology and pathology.

          Glutamate is the principal excitatory neurotransmitter in brain. Our knowledge of the glutamatergic synapse has advanced enormously in the last 10 years, primarily through application of molecular biological techniques to the study of glutamate receptors and transporters. There are three families of ionotropic receptors with intrinsic cation permeable channels [N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate]. There are three groups of metabotropic, G protein-coupled glutamate receptors (mGluR) that modify neuronal and glial excitability through G protein subunits acting on membrane ion channels and second messengers such as diacylglycerol and cAMP. There are also two glial glutamate transporters and three neuronal transporters in the brain. Glutamate is the most abundant amino acid in the diet. There is no evidence for brain damage in humans resulting from dietary glutamate. A kainate analog, domoate, is sometimes ingested accidentally in blue mussels; this potent toxin causes limbic seizures, which can lead to hippocampal and related pathology and amnesia. Endogenous glutamate, by activating NMDA, AMPA or mGluR1 receptors, may contribute to the brain damage occurring acutely after status epilepticus, cerebral ischemia or traumatic brain injury. It may also contribute to chronic neurodegeneration in such disorders as amyotrophic lateral sclerosis and Huntington's chorea. In animal models of cerebral ischemia and traumatic brain injury, NMDA and AMPA receptor antagonists protect against acute brain damage and delayed behavioral deficits. Such compounds are undergoing testing in humans, but therapeutic efficacy has yet to be established. Other clinical conditions that may respond to drugs acting on glutamatergic transmission include epilepsy, amnesia, anxiety, hyperalgesia and psychosis.
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            Early emergence of cortical interneuron diversity in the mouse embryo

            GABAergic interneurons regulate neural circuit activity in the mammalian cerebral cortex. These cortical interneurons are structurally and functionally diverse. Here, we use single-cell transcriptomics to study the origins of this diversity in mouse. We identify distinct types of progenitor cells and newborn neurons in the ganglionic eminences, the embryonic proliferative regions that give rise to cortical interneurons. These embryonic precursors show temporally and spatially restricted transcriptional patterns that lead to different classes of interneurons in the adult cerebral cortex. Our findings suggest that shortly after the interneurons become postmitotic, their diversity is already patent in their diverse transcriptional programs, which subsequently guide further differentiation in the developing cortex.
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              Glutamate and glutamine: a review of in vivo MRS in the human brain.

              Our understanding of the roles that the amino acids glutamate (Glu) and glutamine (Gln) play in the mammalian central nervous system has increased rapidly in recent times. Many conditions are known to exhibit a disturbance in Glu-Gln equilibrium, and the exact relationships between these changed conditions and these amino acids are not fully understood. This has led to increased interest in Glu/Gln quantitation in the human brain in an array of conditions (e.g. mental illness, tumor, neuro-degeneration) as well as in normal brain function. Accordingly, this review has been undertaken to describe the increasing number of in vivo techniques available to study Glu and Gln separately, or pooled as 'Glx'. The present MRS methods used to assess Glu and Gln vary in approach, complexity, and outcome, thus the focus of this review is on a description of MRS acquisition approaches, and an indication of relative utility of each technique rather than brain pathologies associated with Glu and/or Gln perturbation. Consequently, this review focuses particularly on (1) one-dimensional (1)H MRS, (2) two-dimensional (1)H MRS, and (3) one-dimensional (13)C MRS techniques.
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                Author and article information

                Journal
                Mol Med Rep
                Mol Med Rep
                Molecular Medicine Reports
                D.A. Spandidos
                1791-2997
                1791-3004
                October 2019
                06 August 2019
                06 August 2019
                : 20
                : 4
                : 3326-3336
                Affiliations
                [1 ]Department of Burns and Plastic Surgery, and Cleft Lip and Palate Treatment Center, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China
                [2 ]Department of Burns and Plastic Surgery, and Cleft Lip and Palate Treatment Center, Shantou University Medical College, Shantou, Guangdong 515041, P.R. China
                [3 ]Department of Medical Imaging, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, P.R. China
                [4 ]Department of Plastic and Reconstructive Surgery, Central South University Third Xiangya Hospital, Changsha, Hunan 410013, P.R. China
                Author notes
                Correspondence to: Dr Shijie Tang, Department of Burns and Plastic Surgery, and Cleft Lip and Palate Treatment Center, The Second Affiliated Hospital of Shantou University Medical College, 69 Dongxia Road, Shantou, Guangdong 515041, P.R. China, E-mail: tang2302@ 123456163.com ; sjtang3@ 123456stu.edu.cn
                [*]

                Contributed equally

                Article
                mmr-20-04-3326
                10.3892/mmr.2019.10558
                6755240
                31432193
                9ef22183-bd5b-453e-a675-8a190af3edc8
                Copyright: © Xing et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 20 October 2018
                : 19 June 2019
                Categories
                Articles

                cleft palate,high-spatial-resolution magnetic resonance spectroscopy,metabolite

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