Age-dependent decrease of GAD65/67 mRNAs but normal densities of GABAergic interneurons in the brain regions of Shank3 -overexpressing manic mouse model

2017 ◽  
Vol 649 ◽  
pp. 48-54 ◽  
Author(s):  
Bokyoung Lee ◽  
Yinhua Zhang ◽  
Yoonhee Kim ◽  
Shinhyun Kim ◽  
Yeunkum Lee ◽  
...  
Keyword(s):  
Mouse Model ◽  
Brain Regions ◽  
Gabaergic Interneurons ◽  
Age Dependent ◽  
The Brain

Deletion of murine tau gene increases tau aggregation in a human mutant tau transgenic mouse model

2010 ◽  
Vol 38 (4) ◽  
pp. 1001-1005 ◽  
Author(s):  
Kunie Ando ◽  
Karelle Leroy ◽  
Céline Heraud ◽  
Anna Kabova ◽  
Zehra Yilmaz ◽  
...  
Keyword(s):  
Mouse Model ◽  
Transgenic Mouse ◽  
Double Mutant ◽  
Transgenic Mouse Model ◽  
Tau Proteins ◽  
Dependent Manner ◽  
Age Dependent ◽  
Ad Alzheimer’S Disease ◽  
Tau Aggregation ◽  
The Brain

We have reported previously a tau transgenic mouse model (Tg30tau) overexpressing human 4R1N double-mutant tau (P301S and G272V) and that develops AD (Alzheimer's disease)-like NFTs (neurofibrillary tangles) in an age-dependent manner. Since murine tau might interfere with the toxic effects of human mutant tau, we set out to analyse the phenotype of our Tg30tau model in the absence of endogenous murine tau with the aim to reproduce more faithfully a model of human tauopathy. By crossing the Tg30tau line with TauKO (tau-knockout) mice, we have obtained a new mouse line called Tg30×TauKO that expresses only exogenous human double-mutant 4R1N tau. Whereas Tg30×TauKO mice express fewer tau proteins compared with Tg30tau, they exhibit augmented sarkosyl-insoluble tau in the brain and an increased number of Gallyas-positive NFTs in the hippocampus. Taken together, exclusion of murine tau causes accelerated tau aggregation during aging of this mutant tau transgenic model.

scholarly journals Comparison of age‐dependent alterations in thioredoxin 2 and thioredoxin reductase 2 expressions in hippocampi between mice and rats

2021 ◽  
Vol 37 (1) ◽  
Author(s):  
Yeon Ho Yoo ◽  
Dae Won Kim ◽  
Bai Hui Chen ◽  
Hyejin Sim ◽  
Bora Kim ◽  
...  
Keyword(s):  
Thioredoxin Reductase ◽  
Pyramidal Cells ◽  
Brain Regions ◽  
Young Age ◽  
Cresyl Violet ◽  
Western Blots ◽  
Protein Levels ◽  
Cresyl Violet Staining ◽  
Age Dependent ◽  
The Brain

Abstract Background Aging is one of major causes triggering neurophysiological changes in many brain substructures, including the hippocampus, which has a major role in learning and memory. Thioredoxin (Trx) is a class of small redox proteins. Among the Trx family, Trx2 plays an important role in the regulation of mitochondrial membrane potential and is controlled by TrxR2. Hitherto, age-dependent alterations in Trx2 and TrxR2 in aged hippocampi have been poorly investigated. Therefore, the aim of this study was to examine changes in Trx2 and TrxR2 in mouse and rat hippocampi by age and to compare their differences between mice and rats. Results Trx2 and TrxR2 levels using Western blots in mice were the highest at young age and gradually reduced with time, showing that no significant differences in the levels were found between the two subfields. In rats, however, their expression levels were the lowest at young age and gradually increased with time. Nevertheless, there were no differences in cellular distribution and morphology in their hippocampi when it was observed by cresyl violet staining. In addition, both Trx2 and TrxR2 immunoreactivities in the CA1-3 fields were mainly shown in pyramidal cells (principal cells), showing that their immunoreactivities were altered like changes in their protein levels. Conclusions Our current findings suggest that Trx2 and TrxR2 expressions in the brain may be different according to brain regions, age and species. Therefore, further studies are needed to examine the reasons of the differences of Trx2 and TrxR2 expressions in the hippocampus between mice and rats.

scholarly journals Extensive Expression Analysis of Htt Transcripts in Brain Regions from the zQ175 HD Mouse Model Using a QuantiGene Multiplex Assay

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Aikaterini S. Papadopoulou ◽  
Casandra Gomez-Paredes ◽  
Michael A. Mason ◽  
Bridget A. Taxy ◽  
David Howland ◽  
...  
Keyword(s):  
Mouse Model ◽  
Neurodegenerative Disorder ◽  
Simultaneous Detection ◽  
Brain Regions ◽  
Cag Repeat ◽  
Highly Pathogenic ◽  
Exon 2 ◽  
Mouse Tissues ◽  
Exon 1 ◽  
The Brain

Abstract Huntington’s disease (HD) is an inherited neurodegenerative disorder caused by a CAG repeat expansion within exon 1 of the huntingtin (HTT) gene. HTT mRNA contains 67 exons and does not always splice between exon 1 and exon 2 leading to the production of a small polyadenylated HTTexon1 transcript, and the full-length HTT mRNA has three 3′UTR isoforms. We have developed a QuantiGene multiplex panel for the simultaneous detection of all of these mouse Htt transcripts directly from tissue lysates and demonstrate that this can replace the more work-intensive Taqman qPCR assays. We have applied this to the analysis of brain regions from the zQ175 HD mouse model and wild type littermates at two months of age. We show that the incomplete splicing of Htt occurs throughout the brain and confirm that this originates from the mutant and not endogenous Htt allele. Given that HTTexon1 encodes the highly pathogenic exon 1 HTT protein, it is essential that the levels of all Htt transcripts can be monitored when evaluating HTT lowering approaches. Our QuantiGene panel will allow the rapid comparative assessment of all Htt transcripts in cell lysates and mouse tissues without the need to first extract RNA.

scholarly journals Mice with GNAO1 R209H Movement Disorder Variant Display Hyperlocomotion Alleviated by Risperidone

2019 ◽  
Author(s):  
Casandra L. Larrivee ◽  
Huijie Feng ◽  
Josiah A. Quinn ◽  
Vincent S. Shaw ◽  
Jeffrey R. Leipprandt ◽  
...  
Keyword(s):  
Mouse Model ◽  
De Novo ◽  
Neurodevelopmental Disorder ◽  
Clinical Manifestations ◽  
Brain Regions ◽  
Psychomotor Development ◽  
Nucleotide Exchange ◽  
Involuntary Movements ◽  
Gait Abnormality ◽  
The Brain

AbstractNeurodevelopmental disorder with involuntary movements (NEDIM, OMIM: 617493) is a severe, early onset neurological condition characterized by a delay in psychomotor development, hypotonia, and hyperkinetic involuntary movements. Heterozygous de novo mutations in the GNAO1 gene cause NEDIM. Gαo, the gene product of GNAO1, is the alpha subunit of Go, a member of the heterotrimeric Gi/o family of G-proteins. Go is found abundantly throughout the brain but the pathophysiological mechanisms linking Gαo functions to clinical manifestations of GNAO1-related disorders are still poorly understood. One of the most common mutant alleles among the GNAO1 encephalopathies is the c.626G>A or p.Arg209His (R209H) mutation. We developed heterozygous knock-in Gnao1+/R209H mutant mice using CRISPR/Cas9 methodology to assess whether a mouse model could replicate aspects of the NEDIM clinical pattern. Mice carrying the R209H mutation exhibited increased locomotor activity and a modest gait abnormality at 8-12 weeks. In contrast to mice carrying other mutations in Gnao1, the Gnao1+/R209H mice did not show enhanced seizure susceptibility. Levels of protein expression in multiple brain regions were unchanged from WT mice but the nucleotide exchange rate of mutant R209H Gαo was 9 times faster than WT. The atypical neuroleptic risperidone has shown efficacy in a patient with the R209H mutation. It also alleviated the hyperlocomotion phenotype observed in our mouse model but suppressed locomotion in WT mice as well. In this study, we show that Gnao1+/R209H mice mirror elements of the patient phenotype and respond to an approved pharmacological agent.

scholarly journals A Temporal Quantitative Profiling of Newly Synthesized Proteins during Aβ Accumulation

2020 ◽  
Author(s):  
Yuanhui Ma ◽  
Daniel B. McClatchy ◽  
Salvador Martínez-Bartolomé ◽  
Casimir Bamberger ◽  
John R. Yates
Keyword(s):  
Protein Synthesis ◽  
Mitochondrial Respiratory Chain ◽  
Brain Regions ◽  
Age Dependent ◽  
Canonical Amino Acid ◽  
Cellular Pathways ◽  
Pathway Regulation ◽  
The Brain ◽  
Reliable Methods ◽  
Quantitative Profiling

ABSTRACTAccumulation of aggregated amyloid beta (Aβ) in the brain is believed to impair multiple cellular pathways and play a central role in Alzheimer’s disease pathology. But how this process is regulated remains unclear. In theory, measuring protein synthesis is the most direct way to evaluate a cell’s response to stimuli, but to date there have been few reliable methods to do this. To identify the protein regulatory network during the development of Aβ deposition in AD, we applied a new proteomic technique to quantitate newly synthesized protein (NSP) changes in the cerebral cortex and hippocampus of 2, 5 and 9-month-old APP/PS1 AD transgenic mice. This bioorthogonal non-canonical amino acid tagging (BONCAT) analysis combined PALM (Pulse Azidohomoalanine Labeling in Mammals) and HILAQ (Heavy Isotope Labeled AHA Quantitation) to reveal a comprehensive dataset of NSPs prior to and post Aβ deposition, including the identification of proteins not previously associated with AD, and demonstrated that the pattern of differentially expressed NSPs is age-dependent. We also found dysregulated vesicle transportation networks including endosomal subunits, coat protein complex I (COPI) and mitochondrial respiratory chain throughout all timepoints and two brain regions. These results point to a pathological dysregulation of vesicle transportation that occurs prior to Aβ accumulation and the onset of AD symptoms, which may progressively impact the entire protein network and thereby drive neurodegeneration. This study illustrates key pathway regulation responses to the development of AD pathogenesis by directly measuring the changes of protein synthesis and provides unique insights into the mechanisms that underlie AD.

Age-Dependent Increment of Hydroxymethylation in the Brain Cortex in the Triple-Transgenic Mouse Model of Alzheimer's Disease

2014 ◽  
Vol 41 (3) ◽  
pp. 845-854 ◽  
Author(s):  
Carla Cadena-del-Castillo ◽  
Christian Valdes-Quezada ◽  
Francisco Carmona-Aldana ◽  
Clorinda Arias ◽  
Federico Bermúdez-Rattoni ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Transgenic Mouse ◽  
Brain Cortex ◽  
Transgenic Mouse Model ◽  
Model Of Alzheimer’S Disease ◽  
Age Dependent ◽  
Triple Transgenic Mouse ◽  
The Brain

scholarly journals Mechanical alterations of the hippocampus in the APP/PS1 Alzheimer’s disease mouse model

2020 ◽  
Author(s):  
Nelda Antonovaite ◽  
Lianne A. Hulshof ◽  
Christiaan F.M. Huffels ◽  
Elly M. Hol ◽  
Wytse J. Wadman ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Brain Tissue ◽  
Mechanical Testing ◽  
Brain Slices ◽  
Brain Regions ◽  
Tissue Mechanics ◽  
Testing Procedures ◽  
The Brain

AbstractThere is increasing evidence of altered tissue mechanics in neurodegeneration. However, due to difficulties in mechanical testing procedures and the complexity of the brain, there is still little consensus on the role of mechanics in the onset and progression of neurodegenerative diseases. In the case of Alzheimer’s disease (AD), magnetic resonance elastography (MRE) studies have indicated viscoelastic differences in the brain tissue of AD and healthy patients. However, there is a lack of viscoelastic data from contact mechanical testing at higher spatial resolution. Therefore, we report viscoelastic maps of the hippocampus obtained by a dynamic indentation on brain slices from the APP/PS1 mouse model where individual brain regions are resolved. A comparison of viscoelastic parameters shows that regions in the hippocampus of the APP/PS1 mice are significantly stiffer than wild-type (WT) mice and have increased viscous dissipation. Furthermore, indentation mapping at the cellular scale directly on the plaques and their surroundings did not show local alterations in stiffness although overall mechanical heterogeneity of the tissue was high (SD~40%). Therefore, reported mechanical alterations at a tissue scale indicates global remodeling of the brain tissue structure.

scholarly journals Paraoxonase-1 and -3 Protein Expression in the Brain of the Tg2576 Mouse Model of Alzheimer’s Disease

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 339
Author(s):  
Jose Gregorio Salazar ◽  
Judit Marsillach ◽  
Ingrid Reverte ◽  
Bharti Mackness ◽  
Michael Mackness ◽  
...  
Keyword(s):  
Mouse Model ◽  
Protein Expression ◽  
Neurodegenerative Diseases ◽  
Cell Types ◽  
Brain Regions ◽  
Brain Cell ◽  
Paraoxonase 1 ◽  
Tg2576 Mouse ◽  
The Brain ◽  
Brain Cell Types

Background: Brain oxidative lipid damage and inflammation are common in neurodegenerative diseases such as Alzheimer’s disease (AD). Paraoxonase-1 and -3 (PON1 and PON3) protein expression was demonstrated in tissue with no PON1 or PON3 gene expression. In the present study, we examine differences in PON1 and PON3 protein expression in the brain of a mouse model of AD. Methods: we used peroxidase- and fluorescence-based immunohistochemistry in five brain regions (olfactory bulb, forebrain, posterior midbrain, hindbrain and cerebellum) of transgenic (Tg2576) mice with the Swedish mutation (KM670/671NL) responsible for a familial form of AD and corresponding wild-type mice. Results: We found intense PON1 and PON3-positive staining in star-shaped cells surrounding Aβ plaques in all the studied Tg2576 mouse-brain regions. Although we could not colocalize PON1 and PON3 with astrocytes (star-shaped cells in the brain), we found some PON3 colocalization with microglia. Conclusions: These results suggest that (1) PON1 and PON3 cross the blood–brain barrier in discoidal high-density lipoproteins (HDLs) and are transferred to specific brain-cell types; and (2) PON1 and PON3 play an important role in preventing oxidative stress and lipid peroxidation in particular brain-cell types (likely to be glial cells) in AD pathology and potentially in other neurodegenerative diseases as well.

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