Transcription profiling of rat and mouse model of Alzheimers disease after treatment with BDNF
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
SUBMITTER: Giovanni Coppola
PROVIDER: E-GEOD-14522 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:We examined transgenic (TG) mice expressing human APP695 bearing the double Swedish (671KM>NL) and Indiana (717V>F) amyloid precursor protein (APP) mutations. Lentiviral vectors constitutively expressing BDNF-GFP under control of the CMV/Ã-actin hybrid promoter or GFP alone were injected into the entorhinal cortices of TG mice bilaterally at age 6 months, a time point by which neuropathological degeneration and cell loss are established. Age-matched wild-type littermates underwent sham surgery or injection of lentivirus expressing GFP into the entorhinal cortices bilaterally. Experiment Overall Design: 26 Samples total: 4 biological replicates of APP transgenic mice BDNF treated, 4 biological replicates of APP transgenic mice GFP treated, 3 biological replicates of non-trangenic mice sham lesion and 2 biological replicates of non-transgenic mice GFP treated for both tissues: Entorhinal cortex and hippocampus.
2009-02-01 | E-GEOD-14499 | biostudies-arrayexpress
Project description:Patterns of gene expression in the aged entorhinal cortex and hippocampus were examined one month after entorhinal administration of BDNF lentivirus. Whole-genome patterns of expression were examined using Affymetrix arrays four weeks after entorhinal injection of lentiviral-BDNF or GFP injection compared to control subjects. Experiment Overall Design: 27 Samples total: 4 biological replicates of Age rats BDNF treated, 3 biological replicates of Age rats eGFP treated, and 4 biological replicates each of Aged and Young rats controls for the Entorhinal cortex tissue. 2 biological replicates of Age rats BDNF treated, 2 biological replicates of Age rats eGFP treated, and 4 biological replicates each of Age and Young rats controls for the hippocampus tissue.
2009-01-31 | E-GEOD-14505 | biostudies-arrayexpress
Project description:The purpose of the study was to determine the potential role of ATF4 in gene regulation by brain derived neurotrophic factor (BDNF). To achieve this, we compared gene regulation by BDNF in cultured rat hippocampal neurons with or without prior ATF4 knockdown with shRNA. We surveyed cultures after 0,2,4,8 and 16 hrs of exposure to BDNF.
2017-09-09 | E-MTAB-6046 | biostudies-arrayexpress
Project description:Although the Mnks have been known for >15 years, their roles in the regulation of protein synthesis have remained obscure. Here we explore how BDNF stimulates protein synthesis in cortical neurons. Using a combination of pharmacological and genetic approaches, we show that this effect depends on MEK/ERK signaling and on the downstream kinase, Mnk1, which phosphorylates eIF4E. Translation initiation is mediated by the interaction of eIF4E with the m7GTP cap of mRNA and with eIF4G. The latter interaction is inhibited by the interactions of eIF4E with partner proteins such as CYFIP1, which together with its partner, FMRP acts as a translational repressor. We find that BDNF induces the release of CYFIP1 from eIF4E, and that this depends on Mnk1. Finally, using a novel combination of BONCAT and SILAC, we identify the a subset of proteins whose synthesis is upregulated by BDNF signalling via Mnk1 in neurons. The This subset of Mnk1-sensitive proteins are enriched for functions involved in neurotransmission and synaptic plasticity. Additionally, we find significant overlap between our subset of Mnk1 Mnk1-sensitive proteins and proteins encoded by known FMRP-binding mRNAs. Taken together, our data implicate Mnk1 as a key component of BDNF-mediated translational regulation in neurons.
2014-11-06 | PXD001074 | Pride
Project description:This study examined the proteome profile in the hippocampus, medial prefrontal cortex, and striatum of APPswe/PS1dE9 transgenic mice (APP/PS1) model of Alzheimer’s disease compared to wild-type mice. The effect of tocotrienol-rich fraction (TRF), a mixture of vitamin E analogs derived from palm oil supplementation on the proteome profile of APP/PS1 mice hippocampus, medial prefrontal cortex, and striatum was also investigated. The analysis was performed using ultrahigh-performance liquid chromatography coupled with Q Exactive HF Orbitrap mass spectrometry. This study was in hoped to understand the mechanisms of Alzheimer’s disease at proteome level, and pre-emptive activity of TRF to combat the disease.
2019-12-06 | PXD011068 | Pride
Project description:BMSC gene expression profiling was completed to examine the baseline neurotrophin and receptor gene expression in BMSC and to evaulate changes in gene expression in response to NGF or BDNF stimulation In the study, primary BMSC were treated with recombinant human NGF or BDNF for 24 hours. Following treatment, RNA isolated from the BMSC were analyzed using the Human Neurotrophin and Receptor Gene Array HS-018
2010-05-01 | E-GEOD-18537 | biostudies-arrayexpress
Project description:Effect of BDNF on the APP transgenic mouse model of Alzheimer's disease
| PRJNA114487 | ENA
Project description:We examined transgenic (TG) mice expressing human APP695 bearing the double Swedish (671KM>NL) and Indiana (717V>F) amyloid precursor protein (APP) mutations. Lentiviral vectors constitutively expressing BDNF-GFP under control of the CMV/ß-actin hybrid promoter or GFP alone were injected into the entorhinal cortices of TG mice bilaterally at age 6 months, a time point by which neuropathological degeneration and cell loss are established. Age-matched wild-type littermates underwent sham surgery or injection of lentivirus expressing GFP into the entorhinal cortices bilaterally. Keywords: Treatment effect
2009-01-23 | GSE14499 | GEO
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:∆FosB epigenetically regulates target gene expression; however, whether ∆FosB targets the same genes when induced by recurrent seizures in different neurological conditions like Alzheimer's disease (AD) is unclear. We performed hippocampal ChIP-sequencing to identify ∆FosB target genes in APP mice, a model of AD, and in pilocarpine-treated wildtype mice (Pilo mice), a model of epilepsy. Functional domains modulated by ∆FosB target genes are expanded and diversified in APP mice and in Pilo mice (vs respective controls), and primarily involve neuronal excitability and neurotransmission, neurogenesis, chromatin remodeling, and cellular stress and immunity. To identify genes bound by ∆FosB regardless of seizure etiology, we focused on the 442 ∆FosB target genes in both APP and Pilo mice (not respective controls), which related to pathways including membrane potential regulation, glutamatergic signaling, complement activation, neuron-glia population maintenance, and chromatin dynamics. RNA-sequencing and RT-qPCR in independent mice detected altered expression of several ∆FosB targets shared in APP and Pilo mice. Our findings indicate that seizure-induced ∆FosB can bind genes in seizure etiology-dependent patterns, but can also bind genes in patterns regardless of seizure etiology. Understanding factors that influence ∆FosB binding patterns could reveal novel insights into control of gene expression in disorders with recurrent seizures.
2020-04-16 | E-MTAB-8954 | biostudies-arrayexpress