Long-Term Impact of Radiation on the Stem Cell and Oligodendrocyte Precursors in the Brain

Background. The cellular basis of long term radiation damage in the brain is not fully understood. Methods and Findings. We administered a dose of 25Gy to adult rat brains while shielding the olfactory bulbs. Quantitative analyses were serially performed on different brain regions over 15 months. Our data reveal an immediate and permanent suppression of SVZ proliferation and neurogenesis. The olfactory bulb demonstrates a transient but remarkable SVZ-independent ability for compensation and maintenance of the calretinin interneuron population. The oligodendrocyte compartment exhibits a complex pattern of limited proliferation of NG2 progenitors but steady loss of the oligodendroglial antigen O4. As of nine months post radiation, diffuse demyelination starts in all irradiated brains. Counts of capillary segments and length demonstrate significant loss one day post radiation but swift and persistent recovery of the vasculature up to 15 months post XRT. MRI imaging confirms loss of volume of the corpus callosum and early signs of demyelination at 12 months. Ultrastructural analysis demonstrates progressive degradation of myelin sheaths with axonal preservation. Areas of focal necrosis appear beyond 15 months and are preceded by widespread demyelination. Human white matter specimens obtained post-radiation confirm early loss of oligodendrocyte progenitors and delayed onset of myelin sheath fragmentation with preserved capillaries. Conclusions. This study demonstrates that long term radiation injury is associated with irreversible damage to the neural stem cell compartment in the rodent SVZ and loss of oligodendrocyte precursor cells in both rodent and human brain. Delayed onset demyelination precedes focal necrosis and is likely due to the loss of oligodendrocyte precursor

Erythropoietin Amplifies Stroke-Induced Oligodendrogenesis in the Rat

Erythropoietin (EPO), a hematopoietic cytokine, enhances neurogenesis and angiogenesis during stroke recovery. In the present study, we examined the effect of EPO on oligodendrogenesis in a rat model of embolic focal cerebral ischemia.Recombinant human EPO (rhEPO) at a dose of 5,000 U/kg (n = 18) or saline (n = 18) was intraperitoneally administered daily for 7 days starting 24 h after stroke onset. Treatment with rhEPO augmented actively proliferating oligodendrocyte progenitor cells (OPCs) measured by NG2 immunoreactive cells within the peri-infarct white matter and the subventricular zone (SVZ), but did not protect against loss of myelinating oligodendrocytes measured by cyclic nucleotide phosphodiesterase (CNPase) positive cells 7 days after stroke. However, 28 and 42 days after stroke, treatment with rhEPO significantly increased myelinating oligodendrocytes and myelinated axons within the peri-infarct white matter. Using lentivirus to label subventricular zone (SVZ) neural progenitor cells, we found that in addition to the OPCs generated in the peri-infarct white matter, SVZ neural progenitor cells contributed to rhEPO-increased OPCs in the peri-infarct area. Using bromodeoxyuridine (BrdU) for birth-dating cells, we demonstrated that myelinating oligodendrocytes observed 28 days after stroke were derived from OPCs. Furthermore, rhEPO significantly improved neurological outcome 6 weeks after stroke. In vitro, rhEPO increased differentiation of adult SVZ neural progenitor cells into oligodendrocytes and enhanced immature oligodendrocyte cell proliferation.Our in vivo and in vitro data indicate that EPO amplifies stroke-induced oligodendrogenesis that could facilitate axonal re-myelination and lead to functional recovery after stroke

Mood and cognition in healthy older European adults: the Zenith study

YesBackground: The study aim was to determine if state and trait intra-individual measures of everyday affect predict cognitive functioning in healthy older community dwelling European adults (n = 387), aged 55-87 years. Methods: Participants were recruited from centres in France, Italy and Northern Ireland. Trait level and variability in positive and negative affect (PA and NA) were assessed using self-administered PANAS scales, four times a day for four days. State mood was assessed by one PANAS scale prior to assessment of recognition memory, spatial working memory, reaction time and sustained attention using the CANTAB computerized test battery. Results: A series of hierarchical regression analyses were carried out, one for each measure of cognitive function as the dependent variable, and socio-demographic variables (age, sex and social class), state and trait mood measures as the predictors. State PA and NA were both predictive of spatial working memory prior to looking at the contribution of trait mood. Trait PA and its variability were predictive of sustained attention. In the final step of the regression analyses, trait PA variability predicted greater sustained attention, whereas state NA predicted fewer spatial working memory errors, accounting for a very small percentage of the variance (1-2%) in the respective tests. Conclusion: Moods, by and large, have a small transient effect on cognition in this older sample

Brain functional network integrity sustains cognitive function despite atrophy in presymptomatic genetic frontotemporal dementia

Introduction The presymptomatic phase of neurodegenerative disease can last many years, with sustained cognitive function despite progressive atrophy. We investigate this phenomenon in familial frontotemporal dementia (FTD). Methods We studied 121 presymptomatic FTD mutation carriers and 134 family members without mutations, using multivariate data-driven approach to link cognitive performance with both structural and functional magnetic resonance imaging. Atrophy and brain network connectivity were compared between groups, in relation to the time from expected symptom onset. Results There were group differences in brain structure and function, in the absence of differences in cognitive performance. Specifically, we identified behaviorally relevant structural and functional network differences. Structure-function relationships were similar in both groups, but coupling between functional connectivity and cognition was stronger for carriers than for non-carriers, and increased with proximity to the expected onset of disease. Discussion Our findings suggest that the maintenance of functional network connectivity enables carriers to maintain cognitive performance

Temporal dynamics predict symptom onset and cognitive decline in familial frontotemporal dementia

Copyright © 2022 The Authors. Introduction We tested whether changes in functional networks predict cognitive decline and conversion from the presymptomatic prodrome to symptomatic disease in familial frontotemporal dementia (FTD). Methods For hypothesis generation, 36 participants with behavioral variant FTD (bvFTD) and 34 controls were recruited from one site. For hypothesis testing, we studied 198 symptomatic FTD mutation carriers, 341 presymptomatic mutation carriers, and 329 family members without mutations. We compared functional network dynamics between groups, with clinical severity and with longitudinal clinical progression. Results: We identified a characteristic pattern of dynamic network changes in FTD, which correlated with neuropsychological impairment. Among presymptomatic mutation carriers, this pattern of network dynamics was found to a greater extent in those who subsequently converted to the symptomatic phase. Baseline network dynamic changes predicted future cognitive decline in symptomatic participants and older presymptomatic participants. Discussion: Dynamic network abnormalities in FTD predict cognitive decline and symptomatic conversion. Highlights: 1. We investigated brain network predictors of dementia symptom onset. 2. Frontotemporal dementia results in characteristic dynamic network patterns. 3. Alterations in network dynamics are associated with neuropsychological impairment. 4. Network dynamic changes predict symptomatic conversion in presymptomatic carriers. 5. Network dynamic changes are associated with longitudinal cognitive decline.Medical Research Council UK. Grant Numbers: MR/M023664/1, SUAG/092116768 JPND GENFI-PROX. Grant Number: DLR/BMBF 2019-02248 Munich Cluster for Systems Neurology. Grant Number: 390857198 National Institute for Health Research (NIHR) Biomedical Research Centre at Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge. Grant Number: BRC-1215-20014 Cambridge Centre for Parkinson-plus. Grant Number: RG95450 Wellcome Trust. Grant Number: 22025

Influence of pacific on Southern Indian ocean Rossby waves

The sea-surface height anomalies derived from Simple Ocean Data Assimilation (SODA) during 1958-2001, Topex/Poseidon satellite during 1993-2001 and the SODA heat content anomalies (125 m depth) during 1958-2001 are filtered into annual and biennial Rossby wave components using a two-dimensional Finite Impulse Response filter. The filtered Rossby wave components (both annual and biennial) in the southern Pacific and Indian Oceans have considerable strength and variability. The propagation of annual and biennial Rossby waves in the Indonesian through-flow region 12.5°S-7.5°S of the Indian Ocean is in phase with the southern Pacific Ocean waves. So it is speculated that the Pacific Ocean influences the Indian Ocean, especially through the region 17.5°S to 7.5°S and thus the southern Pacific Rossby waves could be an unexplored contributor to the Indian Ocean Rossby waves. We also carried out Fast Fourier Transform (FFT) and wavelet analysis on the tide gauge sea-level data along the Australian coast to support our claim. Filtered annual and biennial components of SODA heat content anomalies (125 m depth) also support these findings

Impact of biannual rossby waves on the indian ocean dipole

Topex/Poseidon sea surface height anomalies during 1993-2002 are decomposed using 2-D finite impulse response filters which showed biannual Rossby waves (BRWs) in the equatorial Indian Ocean (peak at 1.5° S) and in the southern tropical Indian Ocean (peak at 10.5° S) during Indian Ocean Dipole (IOD) years. Anomalous downwelling BRWs in the equatorial Indian Ocean triggered by the wind stress curl-induced Ekman pumping near the eastern boundary started propagating westward from the eastern boundary in July/August 1993 and 1996, i.e., more than one year prior to the formation of the IOD events of 1994 and 1997 respectively. These strong downwelling signals reach the western equatorial Indian Ocean during the peak dipole time. © 2008 IEEE