Dataset Information

Early Stage Alterations in White Matter and Decreased Functional Interhemispheric Hippocampal Connectivity in the 3xTg Mouse Model of Alzheimer's Disease.

ABSTRACT: Alzheimer's disease (AD) is characterized in the late stages by amyloid-β (Aβ) plaques and neurofibrillary tangles. Nevertheless, recent evidence has indicated that early changes in cerebral connectivity could compromise cognitive functions even before the appearance of the classical neuropathological features. Diffusion tensor imaging (DTI), resting-state functional magnetic resonance imaging (rs-fMRI) and volumetry were performed in the triple transgenic mouse model of AD (3xTg-AD) at 2 months of age, prior to the development of intraneuronal plaque accumulation. We found the 3xTg-AD had significant fractional anisotropy (FA) increase and radial diffusivity (RD) decrease in the cortex compared with wild-type controls, while axial diffusivity (AD) and mean diffusivity (MD) were similar. Interhemispheric hippocampal connectivity was decreased in the 3xTg-AD while connectivity in the caudate putamen (CPu) was similar to controls. Most surprising, ventricular volume in the 3xTg-AD was four times larger than controls. The results obtained in this study characterize the early stage changes in interhemispheric hippocampal connectivity in the 3xTg-AD mouse that could represent a translational biomarker to human models in preclinical stages of the AD.

SUBMITTER: Manno FAM

PROVIDER: S-EPMC6440287 | biostudies-other | 2019

REPOSITORIES: biostudies-other

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Early Stage Alterations in White Matter and Decreased Functional Interhemispheric Hippocampal Connectivity in the 3xTg Mouse Model of Alzheimer's Disease.

Manno Francis A M FAM Isla Arturo G AG Manno Sinai H C SHC Ahmed Irfan I Cheng Shuk Han SH Barrios Fernando A FA Lau Condon C

Frontiers in aging neuroscience 20190322

Alzheimer's disease (AD) is characterized in the late stages by amyloid-β (Aβ) plaques and neurofibrillary tangles. Nevertheless, recent evidence has indicated that early changes in cerebral connectivity could compromise cognitive functions even before the appearance of the classical neuropathological features. Diffusion tensor imaging (DTI), resting-state functional magnetic resonance imaging (rs-fMRI) and volumetry were performed in the triple transgenic mouse model of AD (3xTg-AD) at 2 months ...[more]

PMID: 30967770

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Project description:Mesial temporal lobe epilepsy (MTLE), one of the most common types of refractory focal epilepsy, has shown white matter abnormalities both within and beyond the temporal lobe. In particular, the white matter abnormalities in the ipsilateral hemisphere are more obvious than those in the contralateral hemisphere in MTLE, that is, the abnormalities present asymmetrical characteristics. However, very few studies have characterized the white matter microstructure asymmetry in MTLE patients specifically. Thus, we performed diffusion tensor imaging (DTI) to investigate the white matter microstructure asymmetries of patients with MTLE with unilateral hippocampal sclerosis (MTLE-HS). We enrolled 25 MTLE-HS (left MTLE-HS group, n = 13; right MTLE-HS group, n = 12) and 26 healthy controls (HC). DTI data were analyzed by tract-based spatial statistics (TBSS) to test the hemispheric differences across the entire white matter skeleton. We also conducted a two-sample paired t-test for 21 paired region of interests (ROIs) parceled on the basis of the ICBM-DTI-81 white-matter label atlas of bilateral hemispheres to test the hemispheric differences. An asymmetry index (AI) was calculated to further quantify the differences between the left and right paired-ROIs. It was found that the asymmetries of white matter skeletons were significantly lower in the MTLE-HS groups than in the HC group. In particular, the asymmetry traits were moderately reduced in the RMTLE-HS group and obviously reduced in the LMTLE-HS group. In addition, AI was significantly different in the RMTLE-HS group from the LMTLE-HS or HC group in the limbic system and superior longitudinal fasciculus (SLF). The current study found that the interhemispheric white matter asymmetries were significantly reduced in the MTLE-HS groups than in the HC group. The interhemispheric white matter asymmetries are distinctly affected in left and right MTLE-HS groups. The differences in AI among RMTLE-HS, LMTLE-HS, and HC involved the limbic system and SLF, which may have some pragmatic implications for the diagnosis of MTLE and differentiating LMTLE-HS from RMTLE-HS.

Project description:Aims: To investigate the white matter (WM) integrity and hippocampal functional connectivity (FC) in type 2 diabetes mellitus (T2DM) patients without mild cognitive impairment (MCI) by using diffusion tensor imaging (DTI) and resting-state functional magnetic resonance imaging (rs-fMRI), respectively. Methods: Twelve T2DM patients without MCI and 24 age, sex and education matched healthy controls (HC) were recruited. DTI and rs-fMRI data were subsequently acquired on a 3.0T MR scanner. Tract-based spatial statistics (TBSS) combining region of interests (ROIs) analysis was used to investigate the alterations of DTI metrics (fractional anisotropy (FA), mean diffusivity (MD), λ1 and λ23) and FC measurement was performed to calculate hippocampal FC with other brain regions. Cognitive function was evaluated by using Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Brain volumes were also evaluated among these participants. Results: There were no difference of MMSE and MoCA scores between two groups. Neither whole brain nor regional brain volume decrease was revealed in T2DM patients without MCI. DTI analysis revealed extensive WM disruptions, especially in the body of corpus callosum (CC). Significant decreases of hippocampal FC with certain brain structures were revealed, especially with the bilateral frontal cortex. Furthermore, the decreased FA in left posterior thalamic radiation (PTR) and increased MD in the splenium of CC were closely related with the decreased hippocampal FC to caudate nucleus and frontal cortex. Conclusions: T2DM patients without MCI showed extensive WM disruptions and abnormal hippocampal FC. Moreover, the WM disruptions and abnormal hippocampal FC were closely associated. Highlights -T2DM patients without MCI demonstrated no obvious brain volume decrease.-Extensive white matter disruptions, especially within the body of corpus callosum, were revealed with DTI analysis among the T2DM patients.-Despite no MCI in T2DM patients, decreased functional connectivity between hippocampal region and some critical brain regions were detected.-The alterations in hippocampal functional connectivity were closely associated with those of the white matter structures in T2DM patients. This trial was registered to ClinicalTrials.gov (NCT02420470, https://www.clinicaltrials.gov/).

Dataset Information

Early Stage Alterations in White Matter and Decreased Functional Interhemispheric Hippocampal Connectivity in the 3xTg Mouse Model of Alzheimer's Disease.

Publications

Early Stage Alterations in White Matter and Decreased Functional Interhemispheric Hippocampal Connectivity in the 3xTg Mouse Model of Alzheimer's Disease.

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