Striatum and entorhinal cortex atrophy in AD mouse models: MRI comprehensive analysis

Micotti, Edoardo; Paladini, Alessandra; Balducci, Claudia; Tolomeo, Daniele; Frasca, Angelisa; Marizzoni, Moira; Filibian, Marta; Caroli, Anna; Valbusa, Giovanni; Dix, Sophie; O'Neill, Micheal; Ozmen, Laurence; Czech, Christian; Richardson, Jill C.; Frisoni, Giovanni B.; Forloni, Gianluigi

doi:10.1016/j.neurobiolaging.2014.10.027

Cited by 26 publications

(22 citation statements)

References 46 publications

(46 reference statements)

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“…However, we cannot prove that these findings are solely the result of the stem cell treatment ( Figure S1 ). Although a therapeutic effect of MSCs related to the reduction of Aβ deposits was not proven in our study because of the absence of a clear pathological appearance of Aβ, we observed a decrease in the level of Aβ*56 oligomers in the entorhinal cortex, which is involved in spatial as well as working memory formation and is subject to pathological changes in 3xTg-AD mice [ 54 ]. Yeh and colleagues described a significant reduction in the surface area and volume of Glial fibrillary acidic protein (GFAP)-positive cells in the entorhinal cortex of 3xTg-AD mice at very early ages (one month) compared to WT controls.…”

Section: Discussionmentioning

confidence: 98%

Mesenchymal Stem Cells Preserve Working Memory in the 3xTg-AD Mouse Model of Alzheimer’s Disease

Růžička

Kulijewicz-Nawrot

Rodrigez-Arellano

et al. 2016

IJMS

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The transplantation of stem cells may have a therapeutic effect on the pathogenesis and progression of neurodegenerative disorders. In the present study, we transplanted human mesenchymal stem cells (MSCs) into the lateral ventricle of a triple transgenic mouse model of Alzheimer´s disease (3xTg-AD) at the age of eight months. We evaluated spatial reference and working memory after MSC treatment and the possible underlying mechanisms, such as the influence of transplanted MSCs on neurogenesis in the subventricular zone (SVZ) and the expression levels of a 56 kDa oligomer of amyloid β (Aβ*56), glutamine synthetase (GS) and glutamate transporters (Glutamate aspartate transporter (GLAST) and Glutamate transporter-1 (GLT-1)) in the entorhinal and prefrontal cortices and the hippocampus. At 14 months of age we observed the preservation of working memory in MSC-treated 3xTg-AD mice, suggesting that such preservation might be due to the protective effect of MSCs on GS levels and the considerable downregulation of Aβ*56 levels in the entorhinal cortex. These changes were observed six months after transplantation, accompanied by clusters of proliferating cells in the SVZ. Since the grafted cells did not survive for the whole experimental period, it is likely that the observed effects could have been transiently more pronounced at earlier time points than at six months after cell application.

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Section: Discussionmentioning

confidence: 98%

Mesenchymal Stem Cells Preserve Working Memory in the 3xTg-AD Mouse Model of Alzheimer’s Disease

Růžička

Kulijewicz-Nawrot

Rodrigez-Arellano

et al. 2016

IJMS

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“…Finally, to decide which values were reliable to calculate the mean of each group, the spectra with CRLB >30 were discarded. The relative metabolite concentrations were then derived by dividing their fitted amplitudes by that of total creatine, assumed as the internal reference as in previous studies in other AD models …”

Section: Methodsmentioning

confidence: 99%

Progression of Alzheimer's disease and effect of scFv‐h3D6 immunotherapy in the 3xTg‐AD mouse model: An in vivo longitudinal study using Magnetic Resonance Imaging and Spectroscopy

et al. 2020

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Alzheimer's disease (AD) is an incurable disease that affects most of the 47 million people estimated as living with dementia worldwide. The main histopathological hallmarks of AD are extracellular β-amyloid (Aβ) plaques and intracellular neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau protein.In recent years, Aβ-immunotherapy has been revealed as a potential tool in AD treatment. One strategy consists of using single-chain variable fragments (scFvs), which avoids the fragment crystallizable (Fc) effects that are supposed to trigger a microglial response, leading to microhemorrhages and vasogenic edemas, as evidenced in clinical trials with bapineuzumab. The scFv-h3D6 generated by our research group derives from this monoclonal antibody, which targets the N-terminal of the Aβ peptide and recognizes monomers, oligomers and fibrils.In this study, 3xTg-AD mice were intraperitoneally and monthly treated with 100 μg of scFv-h3D6 (a dose of~3.3 mg/kg) or PBS, from 5 to 12 months of age (−mo), the age at which the mice were sacrificed and samples collected for histological and biochemical analyses. During treatments, four monitoring sessions using magnetic resonance imaging and spectroscopy (MRI/MRS) were performed at 5, 7, 9, and 12 months of age. MRI/MRS techniques are widely used in both human and mouse research, allowing to draw an in vivo picture of concrete aspects of the pathology in a non-invasive manner and allowing to monitor its development across time.Compared with the genetic background, 3xTg-AD mice presented a smaller volume in almost all cerebral regions and ages examined, an increase in both the intra and extracellular Aβ 1-42 at 12-mo, and an inflammation process at this age, in both the hippocampus (IL-6 and mIns) and cortex (IL-6). In addition, treatment with scFv-h3D6 partially recovered the values in brain volume, and Aβ, IL-6, and mIns concentrations, among others, encouraging further studies with this antibody fragment.Abbreviations: 3xTg-AD, triple-transgenic mouse model of AD.; 6E10+, mAb-6E10 immunoreactive

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“…On the other hand, transgenic mouse models with AD neuropathology pointed to abnormalities in ongoing EEG activity and epileptiform activity. Transgenic mice with APP and PS1 mutations inducing progressive accumulation of Abeta42 and diffuse plaques in the cerebral cortex, basal ganglia, and thalamus did manifest not only abnormalities in memory processes and ongoing cortical delta activity in the quiet wakefulness (55)(56)(57)(58), but also seizures or subclinical, non-convulsive, and epileptiform EEG activity including cortical and hippocampal spikes and sharp waves (59)(60)(61)(62).…”

Section: Discussionmentioning

confidence: 99%

Abnormalities of Cortical Sources of Resting State Delta Electroencephalographic Rhythms Are Related to Epileptiform Activity in Patients With Amnesic Mild Cognitive Impairment Not Due to Alzheimer's Disease

et al. 2020

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Striatum and entorhinal cortex atrophy in AD mouse models: MRI comprehensive analysis

Cited by 26 publications

References 46 publications

Mesenchymal Stem Cells Preserve Working Memory in the 3xTg-AD Mouse Model of Alzheimer’s Disease

Mesenchymal Stem Cells Preserve Working Memory in the 3xTg-AD Mouse Model of Alzheimer’s Disease

Progression of Alzheimer's disease and effect of scFv‐h3D6 immunotherapy in the 3xTg‐AD mouse model: An in vivo longitudinal study using Magnetic Resonance Imaging and Spectroscopy

Abnormalities of Cortical Sources of Resting State Delta Electroencephalographic Rhythms Are Related to Epileptiform Activity in Patients With Amnesic Mild Cognitive Impairment Not Due to Alzheimer's Disease

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