Abstract
Rett syndrome (RTT) is an X-linked neurodevelopmental disease predominantly caused by mutations of the methyl-CpG-binding protein 2 (MeCP2) gene. Generally, RTT has been attributed to neuron-centric dysfunction. However, increasing evidence has shown that glial abnormalities are also involved in the pathogenesis of RTT. Mice that are MeCP2-null specifically in glial cells showed similar behavioral and/or neuronal abnormalities as those found in MeCP2-null mice, a mouse model of RTT. MeCP2 deficiency in astrocytes impacts the expression of glial intermediate filament proteins such as fibrillary acidic protein (GFAP) and S100 and induces neuron toxicity by disturbing glutamate metabolism or enhancing microtubule instability. MeCP2 deficiency in oligodendrocytes (OLs) results in down-regulation of myelin gene expression and impacts myelination. While MeCP2-deficient microglia cells fail in response to environmental stimuli, release excessive glutamate, and aggravate impairment of the neuronal circuit. In this review, we mainly focus on the progress in determining the role of MeCP2 in glial cells involved in RTT, which may provide further insight into a therapeutic intervention for RTT.
Highlights
Rett Syndrome (RTT) is an X-linked autism spectrum disorder that affects 1 in every 10,000–15,000 newborns in the United States (Chahrour and Zoghbi, 2007)
methyl-CpG-binding protein 2 (MeCP2)-deficient astrocytes that were differentiated from induced pluripotent stem cell lines from Rett syndrome (RTT) patients have negative regulatory effects on neuronal morphology and function (Williams et al, 2014)
The beneficial effect declined when the phagocytic activity of these transplanted cells was inhibited and the ability to clear apoptotic targets was reduced. This result indicated that the phagocytic activity of microglia is impaired in MeCP2-null microglia and that a non-cell autonomous mechanism is involved in spreading the MeCP2-deficient state (Maezawa and Jin, 2010)
Summary
Rett Syndrome (RTT) is an X-linked autism spectrum disorder that affects 1 in every 10,000–15,000 newborns in the United States (Chahrour and Zoghbi, 2007). MeCP2-null microglia and astrocytes have been reported to be toxic to neurons through non-cell autonomous mechanisms, including a slower rate of glutamate (Glu) clearance and release of excessive Glu, as well as glial connexin (Maezawa et al, 2009; Maezawa and Jin, 2010).
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