The olfactory molecular snapshot of Tg2576 mice at early stages of amyloid pathology
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: PXD007813
ORGANISM(S): Mus musculus
PROVIDER: GSE106643 | GEO | 2019/07/01
REPOSITORIES: GEO
Similar Datasets
Project description:Olfaction is often deregulated in Alzheimer´s disease (AD) patients, being also impaired in transgenic Tg2576 AD mouse model, which overexpress the Swedish mutated form of human amyloid precursor protein (APP). However, little is known about the molecular mechanisms that accompany the neurodegeneration of olfactory structures in Tg2576 mice. For that, we have applied proteome- and transcriptome-wide approaches to probe molecular disturbances in the olfactory bulb (OB) dissected from aged Tg2576 mice (18 months of age) respect to age matched wild-type (WT) littermates.
2018-02-14 | GSE103835 | GEO
Project description:Olfaction is often deregulated in Alzheimer´s disease (AD) patients, being also impaired in transgenic Tg2576 AD mouse model, which overexpress the Swedish mutated form of human amyloid precursor protein (APP). However, little is known about the molecular mechanisms that accompany the neurodegeneration of olfactory structures in Tg2576 mice. For that, we have applied proteome-wide approaches to probe molecular disturbances in the olfactory bulb (OB) dissected from Tg2576 mice respect to age matched wild-type littermates (2 and 6 months of age).
2019-06-28 | PXD007813 | Pride
Project description:Olfaction is often deregulated in Alzheimer´s disease (AD) patients, being also impaired in transgenic Tg2576 AD mouse model, which overexpress the Swedish mutated form of human amyloid precursor protein (APP). However, little is known about the molecular mechanisms that accompany the neurodegeneration of olfactory structures in Tg2576 mice. For that, we have applied proteome- and transcriptome-wide approaches to probe molecular disturbances in the olfactory bulb (OB) dissected from aged Tg2576 mice (18 months of age) respect to age matched wild-type (WT) littermates
2017-11-02 | PXD007795 | Pride
Project description:The olfactory molecular snapshot of Tg2576 mice at early stages of amyloid pathology
| PRJNA417496 | ENA
Project description:The amyloidogenic processing of APP to A-beta is known to play a central role in Alzheimer’s disease pathogenesis. Despite this, however, the physiological role of APP and its processing still remains elusive. In the current study we utilzed a transcriptional profiling approach, to determine the pathways that may become dysregulated in the brains of APPswe transgenic mice (Tg2576). As many pathways linked to Alzheimer’s disease are also linked to cholesterol metabolism, we also treated the Tg2576 mice with LXR agonist TO901317, to determine the effects of LXR agonists on the hippocampal transcriptome of Tg2576 mice. We used microarrays to identify gene expression modulated in hippocampus of transgenic TG2576 mice that express human APP containing the Swedish mutation and the transcriptional responses to treatment with an LXR agonist.
2017-08-01 | GSE31624 | GEO
Project description:Olfactory sensory neurons distinguish a large variety of odor molecules and direct the information through their axons to the olfactory bulb, the first site for the processing of olfactory information in the brain. Olfaction is very important for most mammals for the maintenance of a good quality of life. Accumulating evidences endorse that olfactory sensory decline is connected with neurodegenerative disorders including schizophrenia, depression, multiple sclerosis, Huntington's, Alzheimer's and Parkinson's diseases. For several decades, neuroanatomical, volumetric, and histological approaches have been the gold standard techniques employed to characterize the olfactory bulb functionality. Diagnosis and treatment of olfactory dysfunction remain significant health care challenges to society. Novel strategies and clues that assist in the identification of biomarker and drug development for aid in the prevention and cure of neurological diseases are necessary. However, little attention has been focused specifically on the molecular composition of the olfactory bulb from the perspective of proteomics. To this end, an in-depth mapping of the olfactory bulb proteome was carried out using high resolution tandem mass spectrometry, revealing a repertoire of 7,754 proteins. A large proportion of the identified proteins were predicted to be involved in diverse biological processes including signal transduction, metabolism, transport, olfaction and protein synthesis. Pathway analysis of the identified proteins shows that, these proteins are predominantly involved in metabolic and neural processes, chromatin modeling, and synaptic vesicle transport associated with neuronal transmission. In total, our study offers valuable understandings into the molecular composition of the human olfactory bulb proteome that could possibly help neuroscience community to understand the olfactory bulb better and open avenues for intervention strategies for olfactory dysfunction in the future.
2017-08-23 | PXD005629 | Pride
Project description:Extracellular senile plaques of amyloid beta (Abeta) are a pathological hallmark in brain of patients with Alzheimer`s Disease (AD). Abeta is generated by the amyloidogenic processing of the amyloid precursor protein (APP). Concomitant to Abeta load, AD brain is characterized by an increase in protein level and activity of the angiotensin-converting enzyme (ACE). ACE inhibitors are a widely used class of drugs with established benefits for patients with cardiovascular disease. However, the role of ACE and ACE inhibition in the development of Abeta plaques and the process of AD-related neurodegeneration is not clear since ACE was reported to degrade Abeta. To investigate the effect of ACE inhibition on AD-related pathomechanisms, we used Tg2576 mice with neuron-specific expression of APPSwe as AD model. From 12 months of age, substantial Abeta plaque load accumulates in the hippocampus of Tg2576 mice as a brain region, which is highly vulnerable to AD-related neurodegeneration. The effect of central ACE inhibition was studied by treatment of 12 month-old Tg2576 mice for six months with the brain penetrating ACE inhibitor captopril. At an age of 18 months, hippocampal gene expression profiling was performed of captopril-treated Tg2576 mice relative to untreated 18 month-old Tg2576 controls with high Abeta plaque load. As an additional control, we used 12 month-old Tg2576 mice with low Abeta plaque load. Whole genome microarray gene expression profiling revealed gene expression changes induced by the brain-penetrating ACE inhibitor captopril, which could reflect the neuro-regenerative potential of central ACE inhibition. Microarray gene expression profiling was performed of hippocampi isolated from aged, 18 month-old Tg2576 (APPSwe-transgenic) AD mice with high Abeta plaque load relative to age-matched Tg2576 mice, which were treated for 6 months with the centrally active ACE inhibitor captopril. Another study group consisted of 12 month-old Tg2576 mice with low Abeta plaque load. In total, three study groups were analyzed, i.e. (i) 18 month-old untreated Tg2576 mice with high Abeta plaque load, (ii) age-matched Tg2576 mice treated for 6 months with the brain-penetrating ACE inhibitor captopril (20 mg/kg body weight/day in drinking water), and (iii) untreated 12 month-old Tg2576 mice with low Abeta plaque load reflecting the time point when captopril treatment was initiated. Two biological replicates were made of each group, and total hippocampal RNA of four mice was pooled for one gene chip.
2013-05-14 | E-GEOD-46871 | biostudies-arrayexpress
Project description:cAMP plays a dual role in olfaction. It serves as the excitatory second messenger in signaltransduction, but is also required to establish correct axonal targeting toglomeruli in the olfactory bulb. PDE1C regulates cAMP levels in olfactory sensory neurons. Here we extracted RNA from whole olfactory muscosa of PDE1C knockout and control mice. The samples were multiplexed and sequenced using the Illumina Hiseq2500 platform.This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/
2016-02-09 | E-ERAD-438 | biostudies-arrayexpress
Project description:The olfactory system is a part of the mammalian central nervous system and is characterized by neurogenesis and replacement of degenerated neurons. Clinically, it has been reported that the various causes including aging, smoking, and epithelial damage have a high incidence of olfactory impairment. However, the molecular mechanisms underlying these causes-associated defect of olfaction have yet been unclear. To elucidate this problem, we performed micoarray analysis against mouse nasal mucosa and olfactory bulb and compared the transcriptome of them among groups.
2020-05-28 | GSE150694 | GEO
Project description:The goal of this study was the identification of a novel mode of action for this unmet need. Pharmacological tool compounds: suberoylanilide hydroxamic acid (SAHA) and tadalafil, targeting histone deacetylases (HDAC) and phosphodiesterase 5 (PDE5) respectively, were utilized simultaneously for in-vitro and in-vivo Proof-of-Concept (PoC). A synergistic effect was observed in the amelioration of AD signs using the combination therapy in Tg2576 mice. Finally, a therapeutic agent, CM-414, inhibiting simultaneously HDAC2/6 and PDE5 was generated and tested in Tg2576 mice. CM-414 reversed cognitive impairment, reduced amyloid and tau pathology, and rescued dendritic spine density loss in the hippocampus in AD mice. Importantly, the effect obtained was present after a 4-weeks wash-out period.However, to obtain a compound with a safer profile we designed a new compound, CM-695, targeting HDAC6 and PDE9. CM-695 showed similar effect to that of CM-414 after chronic administration to Tg2576 although the effect was not mantained when CM-695 was no longer administered.
2019-07-16 | GSE128422 | GEO