scholarly journals Nitric Oxide Synthase Type 1 Methylation Is Associated With White Matter Microstructure in the Corpus Callosum and Greater Panic Disorder Severity Among Panic Disorder Patients

2021 ◽  
Vol 12 ◽  
Author(s):  
Huazhen Xu ◽  
Yuan Zhong ◽  
Shiting Yuan ◽  
Yun Wu ◽  
Zijuan Ma ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
White Matter ◽  
Nitric Oxide Synthase ◽  
Panic Disorder ◽  
Corpus Callosum ◽  
Symptom Severity ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
Mediating Effect ◽  
Oxide Synthase

Objectives: Methylation of the neuronal nitric oxide synthase (NOS1/nNOS) gene has recently been identified as a promising biomarker of psychiatric disorders. NOS1 plays an essential role in neurite outgrowth and may thus affect the microstructure development of white matter (WM) in the corpus callosum (CC), which is known to be altered in panic disorder (PD). We examined the relationship between NOS1 methylation, WM tracts in the CC, and symptoms based on this finding.Methods: Thirty-two patients with PD and 22 healthy controls (HCs) were recruited after age, gender, and the education level were matched. The cell type used was whole-blood DNA, and DNA methylation of NOS1 was measured at 20 CpG sites in the promoter region. Although 25 patients with PD were assessed with the Panic Disorder Severity Scale (PDSS), diffusion tensor imaging (DTI) scans were only collected from 16 participants with PD.Results: We observed that the PD group showed lower methylation than did the HCs group and positive correlations between the symptom severity of PD and methylation at CpG4 and CpG9. In addition, CpG9 methylation was significantly correlated with the fractional anisotropy (FA) and mean diffusivity (MD) values of the CC and its major components (the genu and the splenium) in the PD group. Furthermore, path analyses showed that CpG9 methylation offers a mediating effect for the association between the MD values of the genu of the CC and PD symptom severity (95% CI = −1.731 to −0.034).Conclusions: The results suggest that CpG9 methylation leads to atypical development of the genu of the CC, resulting in higher PD symptom severity, adding support for the methylation of NOS1 as a future prognostic indicator of PD.

Abstract WP103: Endothelial Nitric Oxide Synthase Regulates White Matter Changes after Stroke

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Xu Cui ◽  
Michael Chopp ◽  
Tao Yan ◽  
Ruizhuo Ning ◽  
Cynthia Roberts ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
White Matter ◽  
Nitric Oxide Synthase ◽  
Endothelial Nitric Oxide Synthase ◽  
Wild Type ◽  
White Matter Damage ◽  
White Matter Changes ◽  
Significant Difference ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Background: Stroke induced white matter damage is associated with neurological functional deficits, but the underlying mechanisms are not well understood. Endothelial nitric oxide synthase knockout (eNOS-/-) mice exhibited a higher mortality, more severe neurological functional deficit, and decreased neurogenesis, angiogenesis and arteriogenesis after stroke than wild type mice. There are no reports as to whether eNOS is related to the white matter change post-stroke. Methods: Adult male C57BL/6 WT and eNOS -/- mice were subjected to permanent middle cerebral artery occlusion (MCAo) by a filament and sacrificed 7 days after MCAo. Functional evaluation, infarct volume measurement, and immunostaining for analysis of white matter changes were performed. Results: There is no significant difference in the infarction volume between wild type and eNOS -/- (wild type : 23.09%±3.32%; eNOS-/-: 27.83%±4.92%, p=0.436, n=9/group). However, eNOS -/- mice showed significantly decreased functional outcome tested by the singal pellet reaching test (wild type: 38.46%%±1.43%, eNOS-/-: 27.45%±2.41%, p=0.0017). eNOS -/- mice also exhibited increased white matter damage compared to wild type mice, including decrease: 1. Axonal density stained by Bielshowsky Silver in the ipsilateral striatal bundles (wild type: 22.06%±3.0%, eNOS-/-: 13.32%±2.18%,, p=0.031), and in the contralateral striatal bundles (wild type: 65.35%±3.97%, eNOS-/-: 29.38%±5.84%, p=0.02); 2. Density of phasphorylated neurofilament by SMI31-immunoflureoscent staining (wild type: 24.11%±2.06%, eNOS-/-: 7.90%±1.70%, p=0.009); 3. The number of CNPase-positive oligodendrocytes in the ischemic border (wild type: 52.23±5.10, eNOS-/-: 35.59±5.33, p=0.041); 4. The number of NG2-positive oligodendrocyte progenitors in the ischemic border (wild type: 26.22±2.31, eNOS-/-: 18.38±1.95, p=0.0187). There is no significant difference in the density of Luxol fast blue stained myelin in the ipsilateral striatal bundles between wild type and eNOS -/- mice (wild type: 25.21%±3.64%; eNOS-/-: 21.39%±6.29%, p=0.260). Conclusions: We are the first to report that eNOS not only regulates vascular changes and neurogenesis, but also plays an important role in white matter changes after stroke.

scholarly journals White matter abnormalities in the corpus callosum with cognitive impairment in Parkinson disease

Neurology ◽  
2018 ◽  
Vol 91 (24) ◽  
pp. e2244-e2255 ◽  
Author(s):  
Ian O. Bledsoe ◽  
Glenn T. Stebbins ◽  
Doug Merkitch ◽  
Jennifer G. Goldman
Keyword(s):  
Cognitive Impairment ◽  
White Matter ◽  
Corpus Callosum ◽  
Parkinson Disease ◽  
Information Transfer ◽  
Diffusion Tensor ◽  
Anterior Segment ◽  
Mean Diffusivity ◽  
Cognitive Domain ◽  
White Matter Abnormalities

ObjectiveTo evaluate microstructural characteristics of the corpus callosum using diffusion tensor imaging (DTI) and their relationships to cognitive impairment in Parkinson disease (PD).MethodsSeventy-five participants with PD and 24 healthy control (HC) participants underwent structural MRI brain scans including DTI sequences and clinical and neuropsychological evaluations. Using Movement Disorder Society criteria, PD participants were classified as having normal cognition (PD-NC, n = 23), mild cognitive impairment (PD-MCI, n = 35), or dementia (PDD, n = 17). Cognitive domain (attention/working memory, executive function, language, memory, visuospatial function) z scores were calculated. DTI scalar values, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD), were established for 5 callosal segments on a midsagittal plane, single slice using a topographically derived parcellation method. Scalar values were compared among participant groups. Regression analyses were performed on cognitive domain z scores and DTI metrics.ResultsParticipants with PD showed increased AD values in the anterior 3 callosal segments compared to healthy controls. Participants with PDD had significantly increased AD, MD, and RD in the anterior 2 segments compared to participants with PD-NC and most anterior segment compared to participants with PD-MCI. FA values did not differ significantly between participants with PD and participants with HC or among PD cognitive groups. The strongest associations for the DTI metrics and cognitive performance occurred in the most anterior and most posterior callosal segments, and also reflected fronto-striatal and posterior cortical type cognitive deficits, respectively.ConclusionsMicrostructural white matter abnormalities of the corpus callosum, as measured by DTI, may contribute to PD cognitive impairment by disrupting information transfer across interhemispheric and callosal–cortical projections.

Abstract 18446: Treatment With Tetrahydrobiopterin Decreases White Matter Injury in a Mouse Model for In Utero Hypoxia in Congenital Heart Disease

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Jennifer Romanowicz ◽  
Ludmila Korotcova ◽  
Paul Morton ◽  
Amrita Cheema ◽  
Vittorio Gallo ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Congenital Heart Disease ◽  
Heart Disease ◽  
White Matter ◽  
Nitric Oxide Synthase ◽  
Congenital Heart ◽  
In Utero ◽  
Complex Congenital Heart Disease ◽  
Brain White Matter ◽  
Oxide Synthase

Introduction: Reduced oxygen delivery in complex congenital heart disease (CHD) can lead to brain white matter (WM) injury in utero. Currently, no treatment exists. Tetrahydrobiopterin (BH4) is a cofactor for neuronal nitric oxide synthase, and in its absence, toxic peroxynitrite production is favored. Hypoxia activates nitric oxide synthase, which reduces BH4 availability. Hypothesis: Decreased BH4 levels underlie WM injury in the fetus with CHD, and treatment with BH4 will reduce this injury. Methods: Mice were divided into three groups: normoxic controls (Nx), hypoxic (Hx), and hypoxic with BH4 treatment (Hx-BH4). Hx and Hx-BH4 mice were kept at 10.5% FiO2 from postnatal day 3 to 11--a period of WM development equivalent to the 3rd trimester in humans. Brain BH4 levels were quantified and compared between Nx (n=11) and Hx (n=12). Densities of cells expressing CNP (marker of oligodendrocytes--cells responsible for myelination) and Caspase3 (apoptosis marker) were quantified in three WM regions and compared between groups (n=3-6 each). Western blot detected myelin basic protein (myelin marker). Results: Brain BH4 levels were depleted in Hx compared to Nx (-38.4%, p=0.02). CNP+ oligodendrocytes increased after Hx compared to Nx (Fig.1a), consistent with hypoxia-induced proliferation seen previously. BH4 treatment did not limit this proliferation (Fig.1a). Hx had increased WM apoptosis (Fig.1b), which decreased with BH4 treatment (Fig.1b). Remarkably, there was no difference in WM caspase3+ cells between Nx and Hx-BH4 (Fig.1b). There was no difference in effect across WM region. Finally, loss of myelin with hypoxia was mitigated by BH4 treatment (Fig.1c). Conclusions: Our results show that suboptimal BH4 levels influence hypoxic WM injury. BH4 treatment of phenylketonuria is safe during pregnancy, thus maternal BH4 therapy is feasible. Our data demonstrate that repurposing BH4 for use during fetal brain development has potential to limit WM injury in CHD.

scholarly journals Corpus Callosum and Cingulum Tractography in Parkinson's Disease

2010 ◽  
Vol 37 (5) ◽  
pp. 595-600 ◽  
Author(s):  
Katie Wiltshire ◽  
Luis Concha ◽  
Myrlene Gee ◽  
Thomas Bouchard ◽  
Christian Beaulieu ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
White Matter ◽  
Corpus Callosum ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
Imaging Method ◽  
Motor Symptoms ◽  
Mri Scans

Background:In Parkinson's disease (PD) cell loss in the substantia nigra is known to result in motor symptoms; however widespread pathological changes occur and may be associated with non-motor symptoms such as cognitive impairment. Diffusion tensor imaging is a quantitative imaging method sensitive to the micro-structure of white matter tracts.Objective:To measure fractional anisotropy (FA) and mean diffusivity (MD) values in the corpus callosum and cingulum pathways, defined by diffusion tensor tractography, in patients with PD, PD with dementia (PDD) and controls and to determine if these measures correlate with Mini-Mental Status Examination (MMSE) scores in parkinsonian patients.Methods:Patients with PD (17 Males [M], 12 Females [F]), mild PDD (5 M, 1F) and controls (8 M, 7F) underwent cognitive testing and MRI scans. The corpus callosum was divided into four regions and the cingulum into two regions bilaterally to define tracts using the program DTIstudio (Johns Hopkins University) using the fiber assignment by continuous tracking algorithm. Volumetric MRI scans were used to measure white and gray matter volumes.Results:Groups did not differ in age or education. There were no overall FA or MD differences between groups in either the corpus callosum or cingulum pathways. In PD subjects the MMSE score correlated with MD within the corpus callosum. These findings were independent of age, sex and total white matter volume.Conclusions:The data suggest that the corpus callosum or its cortical connections are associated with cognitive impairment in PD patients.

scholarly journals Endothelial Nitric Oxide Synthase Regulates White Matter Changes via the BDNF/TrkB Pathway after Stroke in Mice

PLoS ONE ◽  
2013 ◽  
Vol 8 (11) ◽  
pp. e80358 ◽  
Author(s):  
Xu Cui ◽  
Michael Chopp ◽  
Alex Zacharek ◽  
Ruizhuo Ning ◽  
Xiaoshuang Ding ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
White Matter ◽  
Nitric Oxide Synthase ◽  
Endothelial Nitric Oxide Synthase ◽  
White Matter Changes ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

scholarly journals Effects of BDNF Val66Met Polymorphism on White Matter Microalterations of the Corpus Callosum in Patients with Panic Disorder in Korean Populations

2020 ◽  
Vol 17 (10) ◽  
pp. 967-975
Author(s):  
Hyun-Ju Kim ◽  
Minji Bang ◽  
Kang Soo Lee ◽  
Tai Kiu Choi ◽  
Chun Il Park ◽  
...  
Keyword(s):  
White Matter ◽  
Panic Disorder ◽  
Corpus Callosum ◽  
Diffusion Tensor ◽  
The Body ◽  
Imaging Data ◽  
Symptom Scale ◽  
Val66met Polymorphism ◽  
Scale Scores ◽  
Bdnf Val66met Polymorphism

Objective The brain-derived neurotrophic factor (<i>BDNF</i>) Val66Met (rs6265) polymorphism is suggested to be associated with the pathophysiology of anxiety disorders, including panic disorder (PD). Although the fronto-limbic white matter (WM) microstructures have been investigated, the corpus callosum (CC) has not yet been studied regarding its relationship with <i>BDNF</i> Val66Met polymorphism in PD.Methods Ninety-five PD patients were enrolled. The Neuroticism, the Anxiety Sensitivity Inventory-Revised, Panic Disorder Severity Scale, and Beck Depression Inventory-II (BDI-II) were administered. Voxel-wise statistical analysis of diffusion tensor imaging data was performed within the CC regions using Tract-Based Spatial Statistics.Results The GG genotype in <i>BDNF</i> Val66Met polymorphism has significantly higher fractional anisotropy (FA) values of the body and splenium of the CC, neuroticism and depressive symptom scale scores than the non-GG genotype in PD. The FA values of the body of the CC in the two groups were significantly different independent of age, sex, neuroticism, and BDI-II.Conclusion Our findings demonstrate that the <i>BDNF</i> Val66Met polymorphism is associated with WM connectivity of the body and splenium of the CC, and may be related to neuroticism and depressive symptoms in PD. Additionally, the CC connectivity according to BDNF polymorphism may play a role in the pathophysiology of PD.

scholarly journals Microstructural Neuroimaging of Frailty in Cognitively Normal Older Adults

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 176-177
Author(s):  
Qu Tian ◽  
Susan Resnick ◽  
Bennett Landman ◽  
Luigi Ferrucci
Keyword(s):  
Older Adults ◽  
White Matter ◽  
Corpus Callosum ◽  
Gray Matter ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
Carrier Status ◽  
Cognitively Normal ◽  
Frailty Status ◽  
Brain Microstructure

Abstract Physical frailty is an age-related clinical syndrome that is related to adverse health outcomes, including cognitive impairment and dementia. Recent studies have shown structural neuroimaging correlates with frailty. However, most existing evidence relies on brain volumetric measures. Whether brain microstructure is associated with frailty and its spatial distribution have not been explored. In the Baltimore Longitudinal Study of Aging, we identified 776 cognitively normal participants aged 50 and older who had concurrent data on frailty and brain microstructure by diffusion tensor imaging (DTI), including mean diffusivity (MD) of gray matter and fractional anisotropy (FA) of white matter. We first identified neuroimaging markers that were associated with frailty score (0-5) and further examined their relationships with frailty status (0: non-frail, 1-2: pre-frail, 3+: frail) using multivariate linear regression. Models were adjusted for age, sex, race, years of education, and Apolipoprotein E e4 carrier status. DTI-based neuroimaging markers that were associated with frailty status were localized in the supplementary motor area of the frontal lobe, several subcortical regions (putamen, caudate), and body and splenium of corpus callosum. This study demonstrates for the first time that microstructure of both gray and white matter differs by frailty levels in cognitively normal older adults. Brain areas were not widespread, but mostly localized in gray matter subcortical motor areas and white matter corpus callosum. Whether changes in brain microstructure precede future frailty development warrants further investigation.

Diffusion tensor imaging in hyperthyroidism: assessment of microstructural white matter abnormality with a tract-based spatial statistical analysis

2020 ◽  
Vol 61 (12) ◽  
pp. 1677-1683 ◽  
Author(s):  
Kerim Aslan ◽  
Hediye Pinar Gunbey ◽  
Sumeyra Cortcu ◽  
Onur Ozyurt ◽  
Ugur Avci ◽  
...  
Keyword(s):  
Diffusion Tensor Imaging ◽  
White Matter ◽  
Corpus Callosum ◽  
Diffusion Tensor ◽  
Mean Diffusivity ◽  
Imaging Study ◽  
Internal Capsule ◽  
Control Group ◽  
Corona Radiata ◽  
Microstructural Alterations

Background Metabolic, morphological, and functional brain changes associated with a neurological deficit in hyperthyroidism have been observed. However, changes in microstructural white matter (WM), which can explain the underlying pathophysiology of brain dysfunctions, have not been researched. Purpose To assess microstructural WM abnormality in patients with untreated or newly diagnosed hyperthyroidism using tract-based spatial statistics (TBSS). Material and Methods Eighteen patients with hyperthyroidism and 14 age- and sex-matched healthy controls were included in this study. TBSS were used in this diffusion tensor imaging study for a whole-brain voxel-wise analysis of fractional anisotropy, mean diffusivity, axial diffusivity (AD), and radial diffusivity (RD) of WM. Results When compared to the control group, TBSS showed a significant increase in the RD of the corpus callosum, anterior and posterior corona radiata, posterior thalamic radiation, cingulum, superior longitudinal fasciculus, and the retrolenticular region of the internal capsule in patients with hyperthyroidism ( P < 0.05), as well as a significant decrease in AD in the anterior corona radiata and the genu of corpus callosum ( P < 0.05). Conclusion This study showed that more regions are affected by the RD increase than the AD decrease in the WM tracts of patients with hyperthyroidism. These preliminary results suggest that demyelination is the main mechanism of microstructural alterations in the WM of hyperthyroid patients.

Disconnection as a mechanism for social cognition impairment in multiple sclerosis

Neurology ◽  
2017 ◽  
Vol 89 (1) ◽  
pp. 38-45 ◽  
Author(s):  
Sonia Batista ◽  
Carolina Alves ◽  
Otília C. d’Almeida ◽  
Ana Afonso ◽  
Ricardo Félix-Morais ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Social Cognition ◽  
White Matter ◽  
Corpus Callosum ◽  
Diffusion Tensor ◽  
Brain Mri ◽  
Mean Diffusivity ◽  
Uncinate Fasciculus ◽  
Neural Basis ◽  
Cognition Impairment

Objective:To assess the contribution of microstructural normal-appearing white matter (NAWM) damage to social cognition impairment, specifically in the theory of mind (ToM), in multiple sclerosis (MS).Methods:We enrolled consecutively 60 patients with MS and 60 healthy controls (HC) matched on age, sex, and education level. All participants underwent ToM testing (Eyes Test, Videos Test) and 3T brain MRI including conventional and diffusion tensor imaging sequences. Tract-based spatial statistics (TBSS) were applied for whole-brain voxel-wise analysis of fractional anisotropy (FA) and mean diffusivity (MD) on NAWM.Results:Patients with MS performed worse on both tasks of ToM compared to HC (Eyes Test 58.7 ± 13.8 vs 81.9 ± 10.4, p < 0.001, Hedges g −1.886; Videos Test 75.3 ± 9.3 vs 88.1 ± 7.1, p < 0.001, Hedges g −1.537). Performance on ToM tests was correlated with higher values of FA and lower values of MD across widespread white matter tracts. The largest effects (≥90% of voxels with statistical significance) for the Eyes Test were body and genu of corpus callosum, fornix, tapetum, uncinate fasciculus, and left inferior cerebellar peduncle, and for the Videos Test genu and splenium of corpus callosum, fornix, uncinate fasciculus, left tapetum, and right superior fronto-occipital fasciculus.Conclusions:These results indicate that a diffuse pattern of NAWM damage in MS contributes to social cognition impairment in the ToM domain, probably due to a mechanism of disconnection within the social brain network. Gray matter pathology is also expected to have an important role; thus further research is required to clarify the neural basis of social cognition impairment in MS.

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