Project description:We describe age-related molecular and neuronal changes that disrupt mobility or energy balance based on brain region and genetic background. Compared to young mice, aged C57BL/6 mice exhibit marked locomotor (but not energy balance) impairments. In contrast, aged BALB mice exhibit marked energy balance (but not locomotor) impairments. Age-related changes in cerebellar or hypothalamic gene expression accompany these phenotypes. Aging evokes upregulation of immune pattern recognition receptors and cell adhesion molecules. However, these changes do not localize to microglia, the major CNS immunocyte. Consistent with a neuronal role, there is a marked age-related increase in excitatory synapses over the cerebellum and hypothalamus. Functional imaging of these regions is consistent with age-related synaptic impairments. These studies suggest that aging reactivates a developmental program employed during embryogenesis where immune molecules guide synapse formation and pruning. Renewed activity in this program may disrupt excitatory neurotransmission, causing significant behavioral deficits. keywords: aging, C57BL/6, BALB, CBA, hypothalamus, cerebellum, striatum, frontal cortex
Project description:Aging is believed to be the result of alterations of protein expression and accumulation of changes in biomolecules. Although there are numerous reports demonstrating changes in protein expression in brain during aging, only few of them describe global changes in the protein level. Here, we present a deepest quantitative proteomic analysis of three brain regions, hippocampus, cortex and cerebellum, in mice aged 1 and 12 months, using the total protein approach technique. In all the brain regions, both in young and in middle-aged animals, we identified over 6,700 proteins. We found that although the total protein expression in middle-aged brain structures is practically unaffected by aging, there are significant differences between young adult and middle-aged mice in the expression of some receptors and signaling cascade proteins proven to be significant for learning and memory formation. Our analysis demonstrates that hippocampus is the most unstable structure during natural aging and that the first symptoms of weakening of neuronal plasticity may be observed on protein level in middle-aged animals.
Project description:We have used microarrays to analyze gene expression in Parkinson’s disease (PD). We used four different brain regions, including two that are relatively affected in PD (striatum and cortex) and two that are relatively spared (cerebellum and medulla). We show that while differences between brain regions are strong, expression profile differences between PD and controls are much more modest and that genome-wide significant differences are restricted to the striatum and cerebral cortex. RNA (aRNA) was generated from 500ng of total RNA from the medulla (n=15 control brains, n=14 PD brains), striatum (n=15 control brains, n = 15 PD brains), frontal cortex (n=15 control brains, n = 11 PD brains) and cerebellum (n = 14 control brains, n=15 PD brains).
Project description:Comparison of the gene expression profiles of adult human brain samples from frontal cortical regions, including samples from young, middle aged, normal aged, and AlzheimerM-bM-^@M-^Ys disease (AD) brains. Comparison of 12 young (<40yr), 9 middle aged (40-70yr), 16 normal aged (70-94yr), and 4 extremely aged (95-106yr)
Project description:Comparison of the gene expression profiles of adult human brain samples from frontal cortical regions, including samples from young, middle aged, normal aged.
Project description:By looking at the transcriptome of the hypothalamus, frontal cortex and striatum, we studied how the fine balance between the homeostatic and hedonic control of food intake can be influenced by diet
Project description:Analysis of function of CD11c+ cells from middle-aged and young mice at gene level. This experiment provided insight into the different genes that plays roles in inflammation, immune response and mainly arachidonic acid cascade that are differentiall expressed in CD11c+ cells from middle aged and young mice. Total RNA was isolated from pulmonary CD11c cells (separated using magnetic beads) from middle-aged and young mice
Project description:(Phospho)proteomic studies in the human aging brain are based on the comparison between controls of bain aging usually affected by early stages of neurofibrillary tangle (NFT) pathology and subjects with moderate or advanced Alzheimer’s disease (AD).
(Phospho)proteomics using conventional label‐free‐ and SWATH‐MS (Sequential window acquisition of all theoretical fragment ion spectra mass spectrometry) has been assessed in the frontal cortex (FC) of individuals without NFTs and SPs, and comorbidities classified by age (years) in four groups; group 1 (young, 30-44); group 2 (middle-aged: MA, 45-52); group 3 (early-elderly, 64-70); and group 4 (late-elderly, 75-85).
