The Effects of Astrocyte and Oligodendrocyte Lineage Cell Interaction on White Matter Injury under Chronic Cerebral Hypoperfusion. (15th May 2019)

• Record Type: Journal Article
• Authors: Magami, Shunsuke; Miyamoto, Nobukazu; Ueno, Yuji; Hira, Kenichiro; Tanaka, Ryota; Yamashiro, Kazuo; Oishi, Hidenori; Arai, Hajime; Urabe, Takao; Hattori, Nobutaka
• Is Part Of: Neuroscience. Volume 406(2019)
• Page Start: 167
• Page End: 175
• Publication Date: 2019-05-15
• Subjects: astro-oligo interaction -- bilateral carotid arterial stenosis (BCAS) model -- brain derived neurotrophic factor (BDNF) -- white matter injury; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2019.03.004
• Languages: English
• ISSNs: 0306-4522

Abstract

Abstract: Oligodendrocytes (OLGs) differentiate from oligodendrocyte-precursor-cells (OPCs) for myelination in white matter. This differentiation is maintained by cell–cell interactions through trophic factors such as brain-derived-neurotrophic-factor (BDNF). However, differentiation is impaired when white matter injury occurs in a chronic cerebral hypoperfusion model. Thus, we examined the effects of the interaction between astrocyte and oligodendrocyte lineage cells on myelination regarding the mechanism of impairment. A microcoil was applied to the bilateral common carotid arteries in male C57BL/6 mice as an in vivo cerebral chronic hypoperfusion model (BCAS model). A nonlethal concentration of CoCl2 was added to the primary cell culture from the postnatal rat cortex and incubated in vitro . White matter injury progressed in the BCAS model as myelin decreased. The numbers of OPCs and astrocytes increased after the operation, whereas that of OLGs decreased at day 28. BDNF continuously decreased until day 28. Differentiation was disrupted under the stressed conditions in the cell culture, but improved after administration of astrocyte-conditioned medium containing BDNF. Astrocytes with BDNF underwent differentiation, but differentiation was impaired under the stressed conditions due to the reduction of BDNF. We examined S100B regarding the mechanism of impairment. S100B is mainly expressed by mature astrocytes, and has neuroprotective and neurotoxic effects inside and outside of cells. GFAP-positive astrocytes increased in the corpus callosum in the BCAS model, whereas the number of mature astrocytes continued to decrease, resulting in reduced BDNF. The reduction in mature astrocytes due to the discharge of S100B in ischemic conditions caused the reduction in BDNF. Graphical abstract: Unlabelled Image Highlights: White matter injury progresses in chronic cerebral hypoperfusion. White matter injury is caused by impairing oligodendrocyte lineage cells differentiation. The reduction of brain derived neurotrophic factor which is expressed from astrocytes in mature stage is related to its impaired differentiation. Decreasing mature astrocytes leads to the reduction of BDNF in white matter injury.