Dataset Information

Tobacco Smoke-Induced Brain White Matter Myelin Dysfunction: Potential Co-Factor Role of Smoking in Neurodegeneration.

ABSTRACT: BACKGROUND:Meta-analysis studies showed that smokers have increased risk for developing Alzheimer's disease (AD) compared with non-smokers, and neuroimaging studies revealed that smoking damages white matter structural integrity. OBJECTIVE:The present study characterizes the effects of side-stream (second hand) cigarette smoke (CS) exposures on the expression of genes that regulate oligodendrocyte myelin-synthesis, maturation, and maintenance and neuroglial functions. METHODS:Adult male A/J mice were exposed to air (8 weeks; A8), CS (4 or 8 weeks; CS4, CS8), or CS8 followed by 2 weeks recovery (CS8?+?R). The frontal lobes were used for histology and qRT-PCR analysis. RESULTS:Luxol fast blue, Hematoxylin and Eosin stained histological sections revealed CS-associated reductions in myelin staining intensity and narrowing of the corpus callosum. CS exposures broadly decreased mRNA levels of immature and mature oligodendrocyte myelin-associated, neuroglial, and oligodendrocyte-related transcription factors. These effects were more prominent in the CS8 compared with CS4 group, suggesting that molecular abnormalities linked to white matter atrophy and myelin loss worsen with duration of CS exposure. Recovery normalized or upregulated less than 25% of the suppressed genes; in most cases, inhibition of gene expression was either sustained or exacerbated. CONCLUSION:CS exposures broadly inhibit expression of genes needed for myelin synthesis and maintenance. These adverse effects often were not reversed by short-term CS withdrawal. The results support the hypothesis that smoking contributes to white matter degeneration, and therefore could be a key risk factor for a number of neurodegenerative diseases, including AD.

SUBMITTER: Yu R

PROVIDER: S-EPMC5577392 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Tobacco Smoke-Induced Brain White Matter Myelin Dysfunction: Potential Co-Factor Role of Smoking in Neurodegeneration.

Yu Rosa R Deochand Chetram C Krotow Alexander A Leão Raiane R Tong Ming M Agarwal Amit R AR Cadenas Enrique E de la Monte Suzanne M SM

Journal of Alzheimer's disease : JAD 20160101 1

<h4>Background</h4>Meta-analysis studies showed that smokers have increased risk for developing Alzheimer's disease (AD) compared with non-smokers, and neuroimaging studies revealed that smoking damages white matter structural integrity.<h4>Objective</h4>The present study characterizes the effects of side-stream (second hand) cigarette smoke (CS) exposures on the expression of genes that regulate oligodendrocyte myelin-synthesis, maturation, and maintenance and neuroglial functions.<h4>Methods</ ...[more]

PMID: 26639972

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Project description:White matter hyperintensities negatively impact white matter structure and relate to cognitive decline in aging. Diffusion tensor imaging detects changes to white matter microstructure, both within the white matter hyperintensity and extending into surrounding (perilesional) normal-appearing white matter. However, diffusion tensor imaging markers are not specific to tissue components, complicating the interpretation of previous microstructural findings. Myelin water imaging is a novel imaging technique that provides specific markers of myelin content (myelin water fraction) and interstitial fluid (geometric mean T2). Here we combined diffusion tensor imaging and myelin water imaging to examine tissue characteristics in white matter hyperintensities and perilesional white matter in 80 individuals (47 older adults and 33 individuals with chronic stroke). To measure perilesional normal-appearing white matter, white matter hyperintensity masks were dilated in 2 mm segments up to 10 mm in distance from the white matter hyperintensity. Fractional anisotropy, mean diffusivity, myelin water fraction, and geometric mean T2 were extracted from white matter hyperintensities and perilesional white matter. We observed a spatial gradient of higher mean diffusivity and geometric mean T2, and lower fractional anisotropy, in the white matter hyperintensity and perilesional white matter. In the chronic stroke group, myelin water fraction was reduced in the white matter hyperintensity but did not show a spatial gradient in perilesional white matter. Across the entire sample, white matter metrics within the white matter hyperintensity related to whole-brain white matter hyperintensity volume; with increasing white matter hyperintensity volume there was increased mean diffusivity and geometric mean T2, and decreased myelin water fraction in the white matter hyperintensity. Normal-appearing white matter adjacent to white matter hyperintensities exhibits characteristics of a transitional stage between healthy white matter and white matter hyperintensities. This effect was observed in markers sensitive to interstitial fluid, but not in myelin water fraction, the specific marker of myelin concentration. Within the white matter hyperintensity, interstitial fluid was higher and myelin concentration was lower in individuals with more severe cerebrovascular disease. Our data suggests white matter hyperintensities have penumbra-like effects in perilesional white matter that specifically reflect increased interstitial fluid, with no changes to myelin concentration. In contrast, within the white matter hyperintensity there are varying levels of demyelination, which vary based on the severity of cerebrovascular disease. Diffusion tensor imaging and myelin imaging may be useful clinical markers to predict white matter hyperintensity formation, and to stage neuronal damage within white matter hyperintensities.

Dataset Information

Tobacco Smoke-Induced Brain White Matter Myelin Dysfunction: Potential Co-Factor Role of Smoking in Neurodegeneration.

Publications

Tobacco Smoke-Induced Brain White Matter Myelin Dysfunction: Potential Co-Factor Role of Smoking in Neurodegeneration.

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