Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 5 de 5
Filter
Add more filters










Database
Language
Publication year range
1.
Mol Psychiatry ; 20(4): 433-9, 2015 Apr.
Article in English | MEDLINE | ID: mdl-24912493

ABSTRACT

Hippocampal dysfunction in schizophrenia is widely acknowledged, yet the mechanism of such dysfunction remains debated. In this study we investigate the excitatory and inhibitory hippocampal neurotransmission using two complementary methodologies, proton magnetic resonance spectroscopy (MRS) and tissue biochemistry, sampling individuals with schizophrenia in vivo and postmortem hippocampal tissue in vitro. The results show significantly lower glutamate concentrations in hippocampus in schizophrenia, an in vivo finding mirrored by lower GluN1 protein levels selectively in the dentate gyrus (DG) in vitro. In a mouse model with a DG knockout of the GRIN1 gene, we further confirmed that a selective decrease in DG GluN1 is sufficient to decrease the glutamate concentrations in the whole hippocampus. Gamma-aminobutyric acid (GABA) concentrations and GAD67 protein were not significantly different in hippocampus in schizophrenia. Similarly, GABA concentrations in the hippocampi of mice with a DG knockout of the GRIN1 gene were not significantly different from wild type. These findings provide strong evidence implicating the excitatory system within hippocampus in the pathophysiology of schizophrenia, particularly indicating the DG as a site of pathology.


Subject(s)
Dentate Gyrus/metabolism , Glutamic Acid/metabolism , Schizophrenia/pathology , Signal Transduction/physiology , Adolescent , Adult , Animals , Aspartic Acid/analogs & derivatives , Aspartic Acid/metabolism , Disease Models, Animal , Gene Expression Regulation , Humans , Magnetic Resonance Spectroscopy , Mice , Mice, Knockout , Middle Aged , Nerve Tissue Proteins/deficiency , Nerve Tissue Proteins/genetics , Postmortem Changes , Protons , Receptors, N-Methyl-D-Aspartate/deficiency , Receptors, N-Methyl-D-Aspartate/genetics , Young Adult
2.
AJNR Am J Neuroradiol ; 34(4): 797-801, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23079403

ABSTRACT

BACKGROUND AND PURPOSE: Age-related white matter hyperintensities have prognostic implications, but no accepted clinical standard exists for their assessment. We propose a simple objective visual rating system by using 3T brain MR imaging. MATERIALS AND METHODS: MR imaging from 559 participants was processed by using an automated method to determine WMH volumes and evaluated with a new visual rating scale based on the single largest WMH lesion diameter regardless of location. The reproducibility of the visual system was assessed. The association of WMH visual scores and automated volumes was then compared with cognitive scores from the Montreal Cognitive Assessment, which was available for 510 participants. RESULTS: Inter-reader reproducibility was good for subsamples with both high (n=52) and low (n=40) prevalence of large automated WMH volumes (agreement of 67% and 87.5%, κ=0.71 and 0.76, respectively). Correlation between increased WMH and cognitive deficit measurements was equal for our visual ratings and automated volumes (Spearman ρ=0.118 and 0.109; P values=0.008 and 0.014, respectively). The visual scale retained a significant association with MoCA score after adjusting for age, sex, and education (standardized ß=-0.087, P=.042). CONCLUSIONS: We propose a simple visual WMH scoring system suitable for use as a baseline evaluation in clinical practice.


Subject(s)
Brain/pathology , Leukoencephalopathies/pathology , Magnetic Resonance Imaging/methods , Severity of Illness Index , Adult , Aged , Cognition Disorders/epidemiology , Cognition Disorders/pathology , Female , Humans , Leukoencephalopathies/epidemiology , Magnetic Resonance Imaging/standards , Magnetic Resonance Imaging/statistics & numerical data , Male , Middle Aged , Nerve Fibers, Myelinated/pathology , Observer Variation , Prevalence , Prognosis , Reproducibility of Results
3.
AJNR Am J Neuroradiol ; 34(4): 752-7, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23139080

ABSTRACT

BACKGROUND AND PURPOSE: Asymmetry of the hippocampus is regarded as an important clinical finding, but limited data on hippocampal asymmetry are available for the general population. Here we present hippocampal asymmetry data from the Dallas Heart Study determined by automated methods and its relationship to age, sex, and ethnicity. MATERIALS AND METHODS: 3D magnetization-prepared rapid acquisition of gradient echo MR imaging was performed in 2082 DHS-2 participants. The MR images were analyzed by using 2 standard automated brain-segmentation programs, FSL-FIRST and FreeSurfer. Individuals with imaging errors, self-reported stroke, or major structural abnormalities were excluded. Statistical analyses were performed to determine the significance of the findings across age, sex, and ethnicity. RESULTS: At the 90th percentile, FSL-FIRST demonstrated hippocampal asymmetry of 9.8% (95% CI, 9.3%-10.5%). The 90th percentile of hippocampal asymmetry, measured by the difference in right and left hippocampi volume and the larger hippocampus, was 17.9% (95% CI, 17.0%-19.1%). Hippocampal asymmetry increases with age (P=.0216), men have greater asymmetry than women as shown by FSL-FIRST (P=.0036), but ethnicity is not significantly correlated with asymmetry. To confirm these findings, we used FreeSurfer. FreeSurfer showed asymmetry of 4.4% (95% CI, 4.3%-4.7%) normalized to total volume and 8.5% (95% CI, 8.3%-9.0%) normalized by difference/larger hippocampus. FreeSurfer also showed that hippocampal asymmetry increases with age (P=.0024) and that men had greater asymmetry than women (P=.03). CONCLUSIONS: There is a significant degree of hippocampal asymmetry in the population. The data provided will aid in the research, diagnosis, and treatment of temporal lobe epilepsy and other neurologic disease.


Subject(s)
Functional Laterality , Hippocampus/anatomy & histology , Magnetic Resonance Imaging/methods , Magnetic Resonance Imaging/standards , Adult , Epilepsy, Temporal Lobe/pathology , Ethnicity , Female , Humans , Image Processing, Computer-Assisted/methods , Image Processing, Computer-Assisted/standards , Male , Middle Aged , Organ Size , Reference Values , Texas
4.
Nurs Manage ; 30(10): 40-2, 1999 Oct.
Article in English | MEDLINE | ID: mdl-15116446
SELECTION OF CITATIONS
SEARCH DETAIL
...