Genes From a Translational Analysis Support a Multifactorial Nature of White Matter Hyperintensities

Abstract

Supplemental Digital Content is available in the text.

Emerging Evidence for Pathogenesis of Sporadic Cerebral Small Vessel Disease

“…Differential gene effects can be observed in humans with WM hyperintensities (WMH). 25 An magnetic resonance imaging study in patients with SVD showed not only that hypertension could be a predictor of WMH damage in patients with mild stroke but also that salt intake itself is associated with WMH, independent of hypertension. 15 It is well known that there are salt-resistant and salt-sensitive hypertensive patients, the latter of whom has been associated with greater endothelial dysfunction, characterized by defective endothelium-dependent…”

“…Genes differently expressed in brains of SHRSPs of 5, 16, and 21 weeks of age, compared with controls, include those related to glial activity (increased), endothelial tight junctions (reduced), and vascular reactivity (impaired), 23 some of which have also been identified in human gene analysis of WMH. 25 It has been increasingly recognized that oligodendrocyte precursor cells themselves also play a pivotal role in promoting BBB integrity by the secretion of transforming growth factor-β1. 93 Moreover, electron microscopy has demonstrated that oligodendrocyte precursor cells and pericytes directly adhere to and communicate with each other via basal lamina to promote their proliferation and differentiation.…”

“…Эти данные свидетельствуют о том, что не только АГ, но и другие факторы способствуют развитию повре-ждений БВГМ, например взаимодействие генотипа и окружающей среды. У людей с гиперинтенсивными оча-гами в БВГМ (ГБВГМ) можно наблюдать разную работу генов [25]. При проведении исследования с использо-ванием результатов магнитно-резонансной томографии у пациентов с БМЦС продемонстрировали не только то, что АГ может быть предиктором появления ГБВГМ у пациентов с легким инсультом, но и то, что потребление соли само по себе ассоциировано с ГБВГМ, независимо от гипертензии [15].…”

“…свя-занных с активностью глии (увеличение), эндотелиаль-ными плотными контактами (снижение) и реактивно-стью сосудов (нарушение) [23]. Некоторые из этих генов также были идентифицированы при анализе генома людей с ГБВГМ [25]. Было доказано, что клетки-предше-ственники олигодендроцитов сами по себе также играют ключевую роль в обеспечении целостности ГЭБ посред-ством секреции трансформирующего фактора роста-β1 [93].…”

Aberrant epigenetic gene regulation in hippocampal neurogenesis of mouse offspring following maternal exposure to 3,3’-iminodipropionitrile

“…Evidence is also accumulating that mutation of mitochondrial ribosomal protein genes is involved in impaired mitochondrial translation leading to neurological diseases (Boczonadi and Horvath, 2014). Of note, MRPL18, another mitochondrial ribosomal protein gene that was found to be upregulated in active multiple sclerosis lesions (Fischer et al, 2012), was also differentially expressed in brains of young spontaneously hypertensive stroke-prone rats and associated with WMH (Lopez et al, 2015). Taken together, these data provide biological plausibility supporting the role of MRPL38 dysfunction in the pathophysiologic changes in the nervous sys- Fig.…”