scholarly journals Evidence against altered excitatory/inhibitory balance in the posteromedial cortex of young adult APOE E4 carriers: a resting state 1H-MRS study

2021 ◽  
Author(s):  
Alison G Costigan ◽  
Katja Umla-Runge ◽  
C John Evans ◽  
Rachel Raybould ◽  
Kim S Graham ◽  
...  

A strategy to gain insight into early changes that may predispose people to Alzheimer's disease is to study the brains of younger cognitively healthy people that are at increased genetic risk of AD. The Apolipoprotein (APOE) E4 allele is the strongest genetic risk factor for AD, and several neuroimaging studies comparing APOE E4 carriers with non-carriers at age ~20-30 have detected hyperactivity (or reduced deactivation) in posteromedial cortex (PMC), a key hub of the default network (DN) which has a high susceptibility to early amyloid deposition in AD. Transgenic mouse models suggest such early network activity alterations may result from altered excitatory/inhibitory (E/I) balance, but this is yet to be examined in humans. Here we test the hypothesis that PMC fMRI hyperactivity could be underpinned by altered levels of excitatory (glutamate) and/or inhibitory (GABA) neurotransmitters in this brain region. Forty-seven participants (20 APOE E4 carriers and 27 non-carriers) aged 18-25 underwent resting-state proton magnetic resonance spectroscopy (1H-MRS), a non-invasive neuroimaging technique to measure glutamate and GABA in vivo. Metabolites were measured in a PMC voxel of interest and in a comparison voxel in the occipital cortex (OCC). There was no difference in either glutamate or GABA between the E4 carriers and non-carriers in either MRS voxel, nor in the ratio of glutamate to GABA, a measure of E/I balance. Default Bayesian t-tests revealed evidence in support of this null finding. Results suggest that PMC hyperactivity in APOE E4 carriers is unlikely to be associated with, or indeed may precede, alterations in local resting-state PMC neurotransmitters, thus informing the spatio-temporal order and the cause/effect dynamic of neuroimaging differences in APOE E4 carriers.

2019 ◽  
Vol 41 (1-2) ◽  
pp. 67-78 ◽  
Author(s):  
Shiyu Tang ◽  
Su Xu ◽  
Jaylyn Waddell ◽  
Wenjun Zhu ◽  
Rao P. Gullapalli ◽  
...  

Prenatal ethanol exposure alters brain structure, functional connectivity, and behavior in humans and rats. Behavioral changes include deficits in executive function, which requires cooperative activity between the frontal cortices and other brain regions. In this study, we analyzed the functional connectivity and neurochemical levels of the prefrontal cortex (PFC) using resting-state functional magnetic resonance imaging (rsfMRI) and proton magnetic resonance spectroscopy (1H-MRS) in ethanol-exposed (Eth) and control (Ctr) rats. Pregnant Long-Evans rats were fed a liquid diet containing ethanol (2.1–6.46% v/v ethanol) from gestational days 6 to 21 (Eth). Ctr animals received an isocaloric, isonutritive liquid diet. In young adulthood, male and female offspring underwent in vivo MRI using a 7.0-Tesla system. 1H-MRS from the PFC and whole brain rsfMRI were obtained on the animals. Seed-based functional connectivity analysis was performed with seeds placed in the PFC, matching the voxel of MRS. Male, but not female, Eth rats showed less functional connectivity between PFC and dorsal striatum than Ctr animals. In Eth males glucose levels were significantly lower, and in Eth females lower levels of phosphorylcholine but an increased gamma-aminobutyric acid/glutamate ratio were observed in the PFC compared with Ctr animals. Prenatal ethanol alters brain metabolism and functional connectivity of the PFC in a sex-dependent manner.


1994 ◽  
Vol 36 (1) ◽  
pp. 16A-16A
Author(s):  
Floris Groenendaal ◽  
Paula Eken ◽  
Jeroen Van Der Grond ◽  
Karin Rademaker ◽  
Linda S De Vries

2012 ◽  
Vol 113 (5) ◽  
pp. 808-816 ◽  
Author(s):  
Su Xu ◽  
Stephen J. P. Pratt ◽  
Espen E. Spangenburg ◽  
Richard M. Lovering

Skeletal muscle injury is often assessed by clinical findings (history, pain, tenderness, strength loss), by imaging, or by invasive techniques. The purpose of this work was to determine if in vivo proton magnetic resonance spectroscopy (1H MRS) could reveal metabolic changes in murine skeletal muscle after contraction-induced injury. We compared findings in the tibialis anterior muscle from both healthy wild-type (WT) muscles (C57BL/10 mice) and dystrophic ( mdx mice) muscles (an animal model for human Duchenne muscular dystrophy) before and after contraction-induced injury. A mild in vivo eccentric injury protocol was used due to the high susceptibility of mdx muscles to injury. As expected, mdx mice sustained a greater loss of force (81%) after injury compared with WT (42%). In the uninjured muscles, choline (Cho) levels were 47% lower in the mdx muscles compared with WT muscles. In mdx mice, taurine levels decreased 17%, and Cho levels increased 25% in injured muscles compared with uninjured mdx muscles. Intramyocellular lipids and total muscle lipid levels increased significantly after injury but only in WT. The increase in lipid was confirmed using a permeable lipophilic fluorescence dye. In summary, loss of torque after injury was associated with alterations in muscle metabolite levels that may contribute to the overall injury response in mdx mice. These results show that it is possible to obtain meaningful in vivo 1H MRS regarding skeletal muscle injury.


2021 ◽  
Vol 12 ◽  
Author(s):  
Lena Palaniyappan ◽  
Priyadharshini Sabesan ◽  
Xuan Li ◽  
Qiang Luo

Patients with schizophrenia diverge in their clinical trajectories. Such diverge outcomes may result from the resilience provided by antioxidant response system centered on glutathione (GSH). Proton Magnetic Resonance Spectroscopy (1H-MRS) has enabled the precise in vivo measurement of intracortical GSH; but individual studies report highly variable results even when GSH levels are measured from the same brain region. This inconsistency could be due to the presence of distinct subgroups of schizophrenia with varying GSH-levels. At present, we do not know if schizophrenia increases the interindividual variability of intracortical GSH relative to matched healthy individuals. We reviewed all 1H-MRS GSH studies in schizophrenia focused on the Anterior Cingulate Cortex published until August 2021. We estimated the relative variability of ACC GSH levels in patients compared to control groups using the variability ratio (VR) and coefficient of variation ratio (CVR). The presence of schizophrenia significantly increases the variability of intracortical GSH in the ACC (logVR = 0.12; 95% CI: 0.03–0.21; log CVR = 0.15; 95% CI = 0.06–0.23). Insofar as increased within-group variability (heterogeneity) could result from the existence of subtypes, our results call for a careful examination of intracortical GSH distribution in schizophrenia to seek redox-deficient and redox-sufficient subgroups. An increase in GSH variability among patients also indicate that the within-group predictability of adaptive response to oxidative stress may be lower in schizophrenia. Uncovering the origins of this illness-related reduction in the redox system stability may provide novel treatment targets in schizophrenia.


Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3406
Author(s):  
Elisabeth Bumes ◽  
Fro-Philip Wirtz ◽  
Claudia Fellner ◽  
Jirka Grosse ◽  
Dirk Hellwig ◽  
...  

Isocitrate dehydrogenase (IDH)-1 mutation is an important prognostic factor and a potential therapeutic target in glioma. Immunohistological and molecular diagnosis of IDH mutation status is invasive. To avoid tumor biopsy, dedicated spectroscopic techniques have been proposed to detect D-2-hydroxyglutarate (2-HG), the main metabolite of IDH, directly in vivo. However, these methods are technically challenging and not broadly available. Therefore, we explored the use of machine learning for the non-invasive, inexpensive and fast diagnosis of IDH status in standard 1H-magnetic resonance spectroscopy (1H-MRS). To this end, 30 of 34 consecutive patients with known or suspected glioma WHO grade II-IV were subjected to metabolic positron emission tomography (PET) imaging with O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) for optimized voxel placement in 1H-MRS. Routine 1H-magnetic resonance (1H-MR) spectra of tumor and contralateral healthy brain regions were acquired on a 3 Tesla magnetic resonance (3T-MR) scanner, prior to surgical tumor resection and molecular analysis of IDH status. Since 2-HG spectral signals were too overlapped for reliable discrimination of IDH mutated (IDHmut) and IDH wild-type (IDHwt) glioma, we used a nested cross-validation approach, whereby we trained a linear support vector machine (SVM) on the complete spectral information of the 1H-MRS data to predict IDH status. Using this approach, we predicted IDH status with an accuracy of 88.2%, a sensitivity of 95.5% (95% CI, 77.2–99.9%) and a specificity of 75.0% (95% CI, 42.9–94.5%), respectively. The area under the curve (AUC) amounted to 0.83. Subsequent ex vivo 1H-nuclear magnetic resonance (1H-NMR) measurements performed on metabolite extracts of resected tumor material (eight specimens) revealed myo-inositol (M-ins) and glycine (Gly) to be the major discriminators of IDH status. We conclude that our approach allows a reliable, non-invasive, fast and cost-effective prediction of IDH status in a standard clinical setting.


2017 ◽  
Vol 2 (3) ◽  
pp. 310
Author(s):  
Poonam Rana ◽  
Ahmad Raza Khan ◽  
Mamta Aryabhushan Gupta ◽  
Subash Khushu

Whole body radiation exposure induced injury may occur during medical or industrial accidents as well as during terrorist radiation exposure scenario. A lot of information is available on alterations in brain function and metabolism post localised cranial irradiation; changes in brain associated with whole body radiation exposure are still limited. The present study has been conducted to assess early differential effect of low and high whole body radiation exposure on hippocampus neurometabolites using <em>in vivo</em> proton magnetic resonance spectroscopy (1H MRS). Hippocampal 1H MRS was carried out in controls (n = 6) and irradiated mice exposed to 3 Gy, 5 Gy, and 8 Gy of radiation (n = 6 in each group) at different time points i.e., day 0, 1, 3, 5 and 10 post irradiation at 7 T MRI system. Quantitative assessment of the neurometabolites was done using LCModel. The results revealed significant decrease in myoionisitol (mI)/creatine (tCr) and taurine (tau)/tCr in animals exposed to 5 Gy and 8 Gy dose compared to controls. In 3 Gy dose group, none of the metabolites showed significant alterations at any of the time point post irradiation as compared to controls. Overall our findings suggest differential change in hippocampal volume regulatory mechanism associated neuro-metabolites following whole body radiation exposure with maximum reduction in case of high dose group. We speculate that these alterations may be a consequence of oxidative stress, neuro inflammation or systemic inflammatory response following whole body radiation exposure.


2001 ◽  
Vol 280 (3) ◽  
pp. R889-R896 ◽  
Author(s):  
Mark. E. Trump ◽  
Christopher C. Hanstock ◽  
Peter S. Allen ◽  
Daniel Gheorghiu ◽  
Peter W. Hochachka

The human gastrocnemius was examined with and without creatine supplementation under the conditions of rest, ischemic fatigue (IF), and recovery to perturb the pool sizes and equilibrium between phosphocreatine (PCr) and creatine (Cr).1H- and 31P-magnetic resonance spectroscopy (MRS) were used to examine the total creatine (tCr) pool in each of the metabolic states. 31P-MRS monitored the depletion of the PCr peak during IF to <5% of that at rest. 1H-MRS focused on the tCr methyl peak at 3.02 ppm (dipolar coupled triplet), at which point it was expected that the triplet peak intensity would be similar both in IF and rest. Initial 1H-MRS data showed the peak intensity during IF decreased, suggesting a change in tCr pool size. Subsequent studies of transverse relaxation time (T2) revealed that this decline was primarily due to a more rapid T2 decay of the tCr peak in IF (T2 ∼40 ms) compared with at rest (T2 ∼162 ms). Because Cr is the major contributor to tCr in IF, it is possible that there is a pool of Cr displaying reduced mobility in vivo. Moreover, the residual dipolar coupled triplet observed at rest collapsed into a broad singlet during IF, suggestive of significant changes in the ordered environment experienced at rest for PCr compared with when it is converted to Cr during IF. In addition, these data suggest that in 1H-MRS studies whose goals include quantitative estimates of tCr pool sizes, standardized metabolic conditions or careful T2 evaluations will be required.


2019 ◽  
Vol 50 (10) ◽  
pp. 1191-1203 ◽  
Author(s):  
Andrei Manzhurtsev ◽  
O. Vasiukova ◽  
V. Sergeeva ◽  
O. Bozhko ◽  
P. Menshchikov ◽  
...  

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3584-3584
Author(s):  
Carolina Sanz ◽  
Ignasi Barba ◽  
Gustavo Tapia ◽  
Jose-Luis Mate ◽  
Angels Barbera ◽  
...  

Abstract Proton nuclear magnetic resonance spectroscopy (1H MRS) has proven useful in the metabolic characterization of neoplastic tissues both in vitro and in vivo. In vivo 1H MRS can be easily performed in conjunction with conventional MR imaging. Although 1H MRS studies of lymphoma have been performed both in cell lines and animal models, its usefulness as a differential diagnostic tool in lymphoma remains to be explored. T2-filtered high resolution proton magic-angle spinning (HRMAS) MRS of small tissue samples provides sufficient spectral resolution for the identification of chemical cell changes associated with malignancy. HRMAS data from 16 fresh frozen lymph nodes were studied. Histologically, 7 lymph nodes revealed grade I or II follicular lymphoma (FL) and 9 showed diffuse large B cell lymphoma (DLBCL). Each spectrum consisted of the accumulation of 64 scans with a CPMG sequence with an effective T2 delay of 32 ms and an overall experimental time of 6 minutes. Pattern recognition analysis was feasible in all cases except in one FL sample consisting almost exclusively of adipose tissue. Compared with DLBCL, FL cases showed increases in the signal intensity of resonances associted to taurine (3.43 ppm) and decreases in the signal intensity of resonances associated to alanine (1.47 ppm). The mean taurine/alanine ratio was 4.63 (95%SD 1.67) for FL and 1.41 (95%SD 0.69) for DLBCL (P = 0.004). The taurine/alanine ratio proved to be a powerful discriminator between FL and DLBCL at a 2.5 cutpoint, yelding a 90% specificity and an 83% sensitivity to identify DLBCL. Overlapping cases included a case of FL with a diffuse pattern and two cases of DLBCL evolving from indolent lymphomas. The 1H MRS assay proved that FL and DLBCL can be differentiated from a metabolomic standpoint and offers a unique way to explore the underlying biochemistry of malignant transformations. Unlike other techniques, MRS is potentially applicable in vivo and non-invasively in the diagnostic setting. The rapid assessment of nodes or masses before tissue sampling would allow preoperative decisions to be made more efficiently.


Sign in / Sign up

Export Citation Format

Share Document