Project description:Survey of gene expression in ten common inbred strains of laboratory mouse. Seven brain regions examined: amygdala, basal ganglia, cerebellum, frontal cortex, hippocampus, cingulate cortex, olfactory bulb. Keywords: Genetic background and brain region Sample data tables were removed because the ID_REF identifiers did not match the platform IDs
Project description:We aim to analyse high-throughput data deriving from miRNAs expression profiles to thoroughly investigate the miRNAs changes in the four brain regions of adult rats including cerebellum, hippocampus, hypothalamus and cortex
Project description:We aim to analyse high-throughput data deriving from gene expression profiles to thoroughly investigate the transcriptomic changes in the four brain regions of adult rats including cerebellum, hippocampus, hypothalamus and cortex.
Project description:In a wide range of synaptopathies a sex/gender bias in prevalence and clinical course has been reported. Therefore, analysis of the synaptic proteinaceous inventory in different brain regions in males and females is very desirable in understanding the molecular basis of brain function and the etiology of its diseases. In this study we analyzed the synaptic proteome of the prefrontal cortex, hippocampus, striatum and cerebellum in male and female mice. Our efforts should serve as a neurobiological framework to better understand the regional and sex/gender-specific synaptic function both in health and disease.
Project description:To address differences in splicing across brain regions (cerebellum, cortex, hippocampus, and striatum) and sexes, we used long-read Oxford Nanopore Technologies (ONT) RNA sequencing to sequence 40 wild-type mouse brain cDNA libraries from 10 mice and calculated differential expression and transcript usage. We found that there is differential gene expression, differential transcript expression, and differential transcript usage across all brain regions. We found that the brain region with the most differential expression and transcript usage is the cerebellum, potentially driven by differences in cell type composition. Additionally, our findings suggest there is much differential splicing across brain regions and to a lesser extent, within brain regions across sexes.
Project description:Alzheimer’s disease (AD) is a chronic ageing related neurodegenerative disease which is characterized by loss of synapses and neurons in the vulnerable brain regions. Expression perturbations of amyloid β (Aβ) and tau protein in the brain are two hallmarks of AD. Aβ is abnormally generated from amyloid precursor protein (APP) which is broadly distributed in different brain regions including the hippocampus and cortex. It is believed that increased Aβ expression plays a causative role in the early stage of AD pathology. Aβ protein interacts with the signaling pathways that control the phosphorylation of the microtubule-associated protein tau, which eventually disrupts the neuronal circuitry as well as network connectivity leading to neurodegenerative processes observed in AD. In addition, substantial molecular and neurodegenerative changes occur in the initial stage of AD even before the cognitive symptoms are evident, which makes the early diagnosis of AD vital to any timely disease stabilization and treatment. However, despite myriad efforts and substantial progress in the field to decipher the molecular mechanisms of disease onset and its progression, specific causes underlying AD pathology remain ill-defined. There is an urgent need to identify novel mechanism based interventional approaches that can stop, or slow down, the progression of AD. Therefore, it is important to improve the knowledge of the early AD and have a better understanding of the underlying molecular mechanisms induced by Aβ. In this study, we performed comparative quantitative proteomics on different brain regions of 2.5 months old APP/PS1 mice (hippocampus, frontal cortex, parietal cortex and cerebellum) in order to investigate the early stage impact of AD. Although over 5000 proteins were identified in all regions, the proteome response across regions was greatly varied. As expected, the greatest proteome perturbation was detected in the hippocampus and frontal cortex (AD-susceptible brain regions), compared to only 155 changed proteins in the cerebellum (less vulnerable region to AD). Increased expression of APP protein was identified in all brain regions. The expression of the majority of the other proteins between hippocampus and cortex areas was not similar, highlighting differential effects of the disease on different brain regions. A series of AD associated markers and pathways were identified as overexpressed in the hippocampus including glutamatergic synapse, GABAergic synapse, retrograde endocannabinoid signaling, long-term potentiation, and calcium signaling. In contrast, the expression of same proteins and pathways was negatively regulated in frontal and parietal cortex regions. Additionally, an increased expression of proteins associated with the oxidative phosphorylation pathway in hippocampus was not evident in the two cortices. Interestingly, an increased expression of proteins involved with myelination, neurofilament cytoskeleton organization, and glutathione metabolism was identified in cortex areas, while these were reduced in the hippocampus. The results obtained from this study highlight important information on brain region specific protein expression changes occurring in the early stages of AD.
Project description:To discover potential biomarkers of melanoma development and progression, we embarked on studies comparing the glycomic gene profiles of normal human epidermal melanocytes with human metastatic melanoma (MM) cells represented by A375 and G361 cell lines. Glycomic features embody all of those enzymatic, membranous and regulatory proteins that influence glycan ‘sugar’ formation/degradation on a cell. Comparative expression profiling of glycomic genes indicated that several genes were differentially expressed between normal melanocytes and MM cells. We speculate that glycome genes differentially expressed in MM cells help drive malignant and metastatic behavior of MM cells and could potentially serve as a biomarker(s) of melanoma progression.
Project description:We performed an shRNA screen to identify novel ATXN1 protein level regulators in hope of finding some that may improve brainstem function in SCA1. We found that two closely related BTB-ZF transcription factors, ZBTB7A and ZBTB7B, positively regulate ATXN1 levels in vitro and in vivo, with ZBTB7B displaying a more pronounced effect. ZBTB7B regulates ATXN1 by regulating the transcription of RSK3 (RPS6KA2). RSK3 in turn regulates ATXN1 by phosphorylating its serine 776 (S776), a residue critical for ATXN1 stability, which is similar to another one previously identified ATXN1 kinase, MSK1. However, despite the convergent function of the two kinases, each kinase selectively regulates Atxn1 in a brain region-dependent manner; Msk1 predominantly regulates Atxn1 in the cerebellum, while Rsk3 is the predominant regulator of Atxn1 in the brainstem. Our results demonstrate that toxic protein levels can be modulated by different regulators in select brain regions, and hence targeting multiple regulators can expand therapeutic efficacy to rescue multiple degenerating brain areas.