Project description:Schnurri-2 (Shn-2), an NF-kappa B site-binding protein, tightly binds to the enhancers of major histocompatibility complex (MHC) class I genes and inflammatory cytokines, which have been shown to harbor common variant single nucleotide polymorphisms associated with schizophrenia. Shn-2 knockout mice show behavioral abnormalities that strongly resemble those of schizophrenics. We performed gene expression microarray analysis of dentate gyri from Shn-2 knockout and wild-type control mice. Dentate gyrus RNA isolated from six Shn-2 knockout and six control wild-type mice were compared.
Project description:To identify genes responsible for stem and progenitor cells maintenance, we sought here to find genes underlying premature neural aging, and whose deregulated expression could be rescued by running. Through RNA sequencing we analyzed the transcriptomic profiles of the dentate gyrus isolated from Btg1 wild-type or Btg1 knockout adult (two-month-old) mice submitted to physical exercise or sedentary. In Btg1 knockout mice, 545 genes were deregulated, relative to wild-type, while 2081 genes were deregulated by running. We identified 42 genes whose expression was not only down-regulated in the dentate gyrus of Btg1 knockout, but was also counter-regulated to control levels by running in Btg1 knockout mice, vs. sedentary.
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.
Project description:The gene expression patterns in the medial prefrontal cortex of wild-type mice (2W and 12W) were examined using Affymetrix GeneChip arrays.
Project description:The gene expression patterns in the medial prefrontal cortex of Camk2a+/- mice and wild-type mice were examined using Affymetrix GeneChip arrays.
Project description:Gene expression was measured from the dentate gyrus and entorhinal cortex harvested from human postmortem samples. We harvested the dentate gyrus DG from healthy human brains ranging from 33 to 88 years of age. Additionally, from each brain we harvested the entorhinal cortex (EC) as a within-brain control. Using Affymetrix microarray chips we generated gene-expression profiles of each individual tissue samples. DG expression levels were first normalized against the EC, and the normalized DG transcripts were then correlated against age.
Project description:Sanfilippo syndrome type B (MPS III B) is an autosomal recessive, neurodegenerative disease of children, characterized by profound mental retardation and dementia. The primary cause is mutation in the NAGLU gene, resulting in deficiency of N-acetylglucosaminidase and lysosomal accumulation of heparan sulfate. In the mouse model of MPS III B, neurons and microglia display the characteristic vacuolation of lysosomal storage of undegraded substrate, but neurons in the medial entorhinal cortex (MEC) display accumulation of several additional substances. We used whole genome microarray analysis to examine differential gene expression in MEC neurons isolated by laser capture microdissection from Naglu -/- and Naglu +/- mice. Neurons from the lateral entorhinal cortex (LEC) were used as tissue controls. The highest increase in gene expression (6- to 7-fold between mutant and control) in MEC and LEC neurons was that of Lyzs, which encodes lysozyme, but accumulation of lysozyme protein was seen in MEC neurons only. Because of a report that lysozyme induced the formation of hyperphosphorylated tau (P-tau) in cultured neurons, we searched for P-tau by immunohistochemistry. P-tau was found in MEC of Naglu -/- mice, in the same neurons as lysozyme. In older mutant mice, it was also seen in the dentate gyrus, an area important for memory. Electron microscopy of dentate gyrus neurons showed cytoplasmic inclusions of paired helical filaments - P-tau aggregates characteristic of tauopathies, a group of age-related dementias that includes Alzheimer disease. Our findings indicate that the Sanfilippo syndrome type B should also be considered a tauopathy. Two-condition experiment, Naglu-/- (affected) vs. Naglu+/- (unaffected control) of neurons from two adjacent brain regions: medial entorhinal cortex (MEC) and lateral entorhinal cortex (LEC). Biological replicates: 3 MEC Naglu-/-, 3 MEC Naglu+/-, 3 LEC Naglu-/- and 3 LEC Naglu+/-. Comparisons were made between 3 pairs of mutant and control female littermates for MEC and LEC neurons with dye switch duplicates, for a total of 12 microarrays.
