Dynamics of hippocampal neurogenesis in adult humans.
ABSTRACT Adult-born hippocampal neurons are important for cognitive plasticity in rodents. There is evidence for hippocampal neurogenesis in adult humans, although whether its extent is sufficient to have functional significance has been questioned. We have assessed the generation of hippocampal cells in humans by measuring the concentration of nuclear-bomb-test-derived (14)C in genomic DNA, and we present an integrated model of the cell turnover dynamics. We found that a large subpopulation of hippocampal neurons constituting one-third of the neurons is subject to exchange. In adult humans, 700 new neurons are added in each hippocampus per day, corresponding to an annual turnover of 1.75% of the neurons within the renewing fraction, with a modest decline during aging. We conclude that neurons are generated throughout adulthood and that the rates are comparable in middle-aged humans and mice, suggesting that adult hippocampal neurogenesis may contribute to human brain function.
SourceAvailable from: Bharathi Hattiangady[Show abstract] [Hide abstract]
ABSTRACT: Greatly waned neurogenesis, diminished microvasculature, astrocyte hypertrophy and activated microglia are among the most conspicuous structural changes in the aged hippocampus. Because these alterations can contribute to age-related memory and mood impairments, strategies efficacious for mitigating these changes may preserve cognitive and mood function in old age. Resveratrol, a phytoalexin found in the skin of red grapes having angiogenic and antiinflammatory properties, appears ideal for easing these age-related changes. Hence, we examined the efficacy of resveratrol for counteracting age-related memory and mood impairments and the associated detrimental changes in the hippocampus. Two groups of male F344 rats in late middle-age having similar learning and memory abilities were chosen and treated with resveratrol or vehicle for four weeks. Analyses at ~25 months of age uncovered improved learning, memory and mood function in resveratrol-treated animals but impairments in vehicle-treated animals. Resveratrol-treated animals also displayed increased net neurogenesis and microvasculature, and diminished astrocyte hypertrophy and microglial activation in the hippocampus. These results provide novel evidence that resveratrol treatment in late middle age is efficacious for improving memory and mood function in old age. Modulation of the hippocampus plasticity and suppression of chronic low-level inflammation appear to underlie the functional benefits mediated by resveratrol.Scientific Reports 01/2015; 5:8075. DOI:10.1038/srep08075 · 5.08 Impact Factor
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ABSTRACT: Osteocytes form an extensive cellular network throughout the hard tissue matrix of the skeleton, which is known to regulate skeletal structure. However due to limitations in imaging techniques, the magnitude and complexity of this network remains undefined. We have used data from recent papers obtained by new imaging techniques, in order to estimate absolute and relative quantities of the human osteocyte network and form a more complete understanding of the extent and nature of this network. We estimate that the total number of osteocytes within the average adult human skeleton is ~42 billion and that the total number osteocyte dendritic projections from these cells is ~3.7 trillion. Based on prior measurements of canalicular density and a mathematical model of osteocyte dendritic process branching, we calculate that these cells form a total of 23 trillion connections with each other and with bone surface cells. We estimate the total length of all osteocytic processes connected end-to-end to be 175,000km. Furthermore, we calculate that the total surface area of the lacuno-canalicular system is 215m(2). However, the residing osteocytes leave only enough space for 24mL extracellular fluid. Calculations based on measurements in lactation-induced murine osteocytic osteolysis indicate a potential total loss of ~16,000mm(3) (16mL) bone by this process in the human skeleton. Finally, based on the average speed of remodelling in the adult, we calculate that 9.1 million osteocytes are replenished throughout the skeleton on a daily basis, indicating the dynamic nature of the osteocyte network. We conclude that the osteocyte network is a highly complex communication network, and is much more vast than commonly appreciated. It is at the same order of magnitude as current estimates of the size of the neural network in the brain, even though the formation of the branched network differs between neurons and osteocytes. Furthermore, continual replenishment of large numbers of osteocytes in the process of remodelling allows therapeutic changes to the continually renewed osteoblast population to be rapidly incorporated into the skeleton. Copyright © 2015. Published by Elsevier Inc.Bone 02/2015; 75. DOI:10.1016/j.bone.2015.02.016 · 4.46 Impact Factor