N-Acetyl and Glutamatergic Neurometabolites in Perisylvian Brain Regions of Methamphetamine Users.

Background:Methamphetamine induces neuronal N-acetyl-aspartate synthesis in preclinical studies. In a preliminary human proton magnetic resonance spectroscopic imaging investigation, we also observed that N-acetyl-aspartate+N-acetyl-aspartyl-glutamate in right inferior frontal cortex correlated with years of heavy methamphetamine abuse. In the same brain region, glutamate+glutamine is lower in methamphetamine users than in controls and is negatively correlated with depression. N-acetyl and glutamatergic neurochemistries therefore merit further investigation in methamphetamine abuse and the associated mood symptoms. Methods:Magnetic resonance spectroscopic imaging was used to measure N-acetyl-aspartate+N-acetyl-aspartyl-glutamate and glutamate+glutamine in bilateral inferior frontal cortex and insula, a neighboring perisylvian region affected by methamphetamine, of 45 abstinent methamphetamine-dependent and 45 healthy control participants. Regional neurometabolite levels were tested for group differences and associations with duration of heavy methamphetamine use, depressive symptoms, and state anxiety. Results:In right inferior frontal cortex, N-acetyl-aspartate+N-acetyl-aspartyl-glutamate correlated with years of heavy methamphetamine use (r = +0.45); glutamate+glutamine was lower in methamphetamine users than in controls (9.3%) and correlated negatively with depressive symptoms (r = -0.44). In left insula, N-acetyl-aspartate+N-acetyl-aspartyl-glutamate was 9.1% higher in methamphetamine users than controls. In right insula, glutamate+glutamine was 12.3% lower in methamphetamine users than controls and correlated negatively with depressive symptoms (r = -0.51) and state anxiety (r = -0.47). Conclusions:The inferior frontal cortex and insula show methamphetamine-related abnormalities, consistent with prior observations of increased cortical N-acetyl-aspartate in methamphetamine-exposed animal models and associations between cortical glutamate and mood in human methamphetamine users

Common promoter variants of the NDUFV2 gene do not confer susceptibility to schizophrenia in Han Chinese

<p>Abstract</p> <p>Background</p> <p>The NADH-ubiquinone oxidoreductase flavoprotein gene (<it>NDUFV2</it>), which encodes a 24 kD mitochondrial complex I subunit, has been reported to be positively associated with schizophrenia and bipolar disorder in different populations.</p> <p>Methods</p> <p>We genotyped the promoter variants of this gene (rs6506640 and rs1156044) by direct sequencing in 529 unrelated Han Chinese schizophrenia patients and 505 matched controls. Fisher's Exact test was performed to assess whether these two reported single nucleotide polymorphisms (SNPs) confer susceptibility to schizophrenia in Chinese.</p> <p>Results</p> <p>Allele, genotype and haplotype comparison between the case and control groups showed no statistical significance, suggesting no association between the <it>NDUFV2 </it>gene promoter variants and schizophrenia in Han Chinese.</p> <p>Conclusion</p> <p>The role of NDUFV2 played in schizophrenia needs to be further studied. Different racial background and/or population substructure might account for the inconsistent results between studies.</p

Blocking Ion Migration Stabilizes the High Thermoelectric Performance in Cu2Se Composites

The applications of mixed ionic–electronic conductors are limited due to phase instability under a high direct current and large temperature difference. Here, it is shown that Cu2Se is stabilized through regulating the behaviors of Cu+ ions and electrons in a Schottky heterojunction between the Cu2Se host matrix and in‐situ‐formed BiCuSeO nanoparticles. The accumulation of Cu+ ions via an ionic capacitive effect at the Schottky junction under the direct current modifies the space‐charge distribution in the electric double layer, which blocks the long‐range migration of Cu+ and produces a drastic reduction of Cu+ ion migration by nearly two orders of magnitude. Moreover, this heterojunction impedes electrons transferring from BiCuSeO to Cu2Se, obstructing the reduction reaction of Cu+ into Cu metal at the interface and hence stabilizes the β‐Cu2Se phase. Furthermore, incorporation of BiCuSeO in Cu2Se optimizes the carrier concentration and intensifies phonon scattering, contributing to the peak figure of merit ZT value of ≈2.7 at 973 K and high average ZT value of ≈1.5 between 400 and 973 K for the Cu2Se/BiCuSeO composites. This discovery provides a new avenue for stabilizing mixed ionic–electronic conduction thermoelectrics, and gives fresh insights into controlling ion migration in these ionic‐transport‐dominated materials.The space‐charge region between Cu2Se host matrix and in‐situ‐formed BiCuSeO under a direct current causes drastic suppression of the Cu+ ion migration in such composites and obstructs the reduction reaction of Cu+ into Cu metal. This, together with the effective regulation of carrier concentration as well as enhanced interfacial phonon scattering, greatly stabilizes the improved thermoelectric performance.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163457/2/adma202003730-sup-0001-SuppMat.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163457/3/adma202003730_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163457/1/adma202003730.pd

The relationship between Cho/NAA and glioma metabolism: implementation for margin delineation of cerebral gliomas

BACKGROUND: The marginal delineation of gliomas cannot be defined by conventional imaging due to their infiltrative growth pattern. Here we investigate the relationship between changes in glioma metabolism by proton magnetic resonance spectroscopic imaging ((1)H-MRSI) and histopathological findings in order to determine an optimal threshold value of choline/N-acetyl-aspartate (Cho/NAA) that can be used to define the extent of glioma spread. METHOD: Eighteen patients with different grades of glioma were examined using (1)H-MRSI. Needle biopsies were performed under the guidance of neuronavigation prior to craniotomy. Intraoperative magnetic resonance imaging (MRI) was performed to evaluate the accuracy of sampling. Haematoxylin and eosin, and immunohistochemical staining with IDH1, MIB-1, p53, CD34 and glial fibrillary acidic protein (GFAP) antibodies were performed on all samples. Logistic regression analysis was used to determine the relationship between Cho/NAA and MIB-1, p53, CD34, and the degree of tumour infiltration. The clinical threshold ratio distinguishing tumour tissue in high-grade (grades III and IV) glioma (HGG) and low-grade (grade II) glioma (LGG) was calculated. RESULTS: In HGG, higher Cho/NAA ratios were associated with a greater probability of higher MIB-1 counts, stronger CD34 expression, and tumour infiltration. Ratio threshold values of 0.5, 1.0, 1.5 and 2.0 appeared to predict the specimens containing the tumour with respective probabilities of 0.38, 0.60, 0.79, 0.90 in HGG and 0.16, 0.39, 0.67, 0.87 in LGG. CONCLUSIONS: HGG and LGG exhibit different spectroscopic patterns. Using (1)H-MRSI to guide the extent of resection has the potential to improve the clinical outcome of glioma surgery