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Aging brain
About: Aging brain is a research topic. Over the lifetime, 1255 publications have been published within this topic receiving 66405 citations.
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TL;DR: These observations support the hypothesis of transneuronal spread of neurofibrillary changes from the DR to its interconnected cortical brain areas and indicate that the supratrochlear subnucleus of the DR is affected by neurofibillary changes before the transentorhinal cortex during the disease process underlying AD.
Abstract: AIMS Alzheimer's disease (AD) is a progressive and irreversible disease. There is strong evidence that the progression of the phospho-tau neurofibrillary cytoskeletal changes, rather than the beta-amyloid burden, is crucial in determining the severity of the dementia in AD. The Braak and Braak staging system (BB) focuses mainly on the cortical cytoskeletal pathology and classifies this progressive pathology into six stages, spreading from the transentorhinal region to primary cortices. Although it is reported elsewhere that the midbrain's dorsal raphe nucleus (DR), which is connected with those areas of the cerebral cortex undergoing early changes during BB I and II, exhibits AD-related cytoskeletal pathology, this nucleus has not been considered by the BB. METHODS To determine during which BB stage and how frequently the DR is affected by AD-related neurofibrillary changes, we studied the DR of 118 well-characterized individuals of the Brain Bank of the Brazilian Aging Brain Study Group categorized according to the BB. Thirty-eight of these individuals were staged as BB = 0, and 80 as BB >or= 1. RESULTS In all of the BB >or= 1 individuals (cortical neurofibrillary changes were present at least in the transentorhinal region) and in more than 1/5 of the BB = 0 individuals neurofibrillary changes were detected in the supratrochlear subnucleus of the DR. CONCLUSIONS These observations: (i) support the hypothesis of transneuronal spread of neurofibrillary changes from the DR to its interconnected cortical brain areas; and (ii) indicate that the supratrochlear subnucleus of the DR is affected by neurofibrillary changes before the transentorhinal cortex during the disease process underlying AD.
188 citations
TL;DR: Analysis of brainstem and cortical speech-evoked brain responses suggests aging negatively impacts speech listening abilities by distorting the hierarchy of speech representations, reducing neural flexibility through increased neural redundancy, and ultimately impairing the acoustic-phonetic mapping necessary for robust speech understanding.
188 citations
TL;DR: Observations identify ApoD as an acute response protein with a protective and therefore beneficial function mediated by the control of peroxidated lipids, and its transcriptional up‐regulation in the brain upon oxidative insult.
Abstract: Many nervous system pathologies are associated with increased levels of apolipoprotein D (ApoD), a lipocalin also expressed during normal development and aging. An ApoD homologous gene in Drosophila, Glial Lazarillo, regulates resistance to stress, and neurodegeneration in the aging brain. Here we study for the first time the protective potential of ApoD in a vertebrate model organism. Loss of mouse ApoD function increases the sensitivity to oxidative stress and the levels of brain lipid peroxidation, and impairs locomotor and learning abilities. Human ApoD overexpression in the mouse brain produces opposite effects, increasing survival and preventing the raise of brain lipid peroxides after oxidant treatment. These observations, together with its transcriptional up-regulation in the brain upon oxidative insult, identify ApoD as an acute response protein with a protective and therefore beneficial function mediated by the control of peroxidated lipids.
187 citations
TL;DR: The study by Hara et al. in PNAS synergizes with recent discoveries, revealing a key role of mitochondria regulating synaptic transmission, brain function, and cognition in aging.
Abstract: A revolution in our understanding of brain development, adult brain function, senescence, and disease has emerged from the recognition of structural and functional plasticity within the mammalian brain (1). For example, the role of brain-derived neurotrophic factor (BDNF) and other hormonal factors that mediate neurogenesis, as well as synaptic and dendritic plasticity in psychiatric disorders (2), has revealed unforeseen neuronal regulatory mechanisms. These build on a growing dynamic conception of brain architecture that complements the understanding of synaptic transmission. This, we are also discovering, is a plastic event altered by both structural and functional remodeling of the synapse. However, little is known about the role of mitochondria in regulating synaptic transmission, and less yet about their implications for cognitive function and memory decline in the aging brain (3). The study by Hara et al. (4) in PNAS synergizes with recent discoveries, revealing a key role of mitochondria regulating synaptic transmission, brain function, and cognition in aging.
187 citations
TL;DR: These data are the first linking inflammation‐related transcription factor NF‐κB‐DNA binding to up‐regulation of transcription from a key inflammatory gene, COX‐2, in both normally aging brain and in AD‐affected neocortex.
Abstract: Cyclooxygenase-2 (COX-2; EC 1.14.99.1) RNA message abundance in 25 control and Consortium to Establish a Registry for Alzheimer's Disease (CERAD)-confirmed sporadic Alzheimer's disease (AD) brains is remarkably heterogeneous when compared with 55 other AD brain RNA message levels that were previously characterized (Lukiw and Bazan: J Neurosci Res 50:937–945, 1997). Examination of nuclear protein extracts (NPXTs) that were derived from control and AD-affected brain neocortical nuclei (n = 20; age range, 60–82 years; postmortem interval, 0.5–6.5 hours) by using gel shift, gel supershift, and cold oligonucleotide competition assay revealed a highly significant relationship between the extent of inflammatory transcription factor, nuclear factor (NF)-κB: DNA binding and the abundance of the COX-2 RNA signal (P 0.045). These data are the first linking inflammation-related transcription factor NF-κB-DNA binding to up-regulation of transcription from a key inflammatory gene, COX-2, in both normally aging brain and in AD-affected neocortex.
Systematic deletion of NF-κB-DNA binding sites in human COX-2 promoter constructs attenuates COX-2 transcriptional induction by mediators of inflammation. Strong NF-κB-DNA binding has been reported previously to temporally precede COX-2 gene transcription in human epithelial (A549), hamster B-cell (HIT-T15), human endothelial (HUVEC), human lymphoblast (IM9), human fibroblast (IMR90), rat glioma/mouse neuroblastoma (NG108–15), human keratinocyte (NHEK), mouse fibroblast (NIH 3T3), rat neuroblastoma (SH-SY5Y) cell lines and in mouse and rat brain hippocampus, indicating a highly conserved inflammatory signaling pathway that is common to diverse species and cell types. The mouse, rat, and human COX-2 immediate promoters, despite 7.5 × 107 years of DNA sequence divergence, each retain multiple recognition sites specific for NF-κB-DNA binding. These data suggest that basic gene induction mechanisms, which have been conserved over long periods of evolution, that increase NF-κB-DNA binding may be fundamental in driving transcription from inflammation-related genes, such as COX-2, that operate in stressed tissues, in normally aging cell lines, and in neurodegenerative disorders that include AD brain. J. Neurosci. Res. 53:583–592, 1998. © 1998 Wiley-Liss, Inc.
185 citations