Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033036 (APC)
 10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

White matter injury (WMI) of prematurity is associated with a spectrum of neurological disorders ranging from mild cognitive and behavioral deficits to cerebral palsy. Translational studies have implicated impaired oligodendrocyte development after hypoxia as the primary cause of WMI, but the underlying mechanisms remain poorly understood. The goal of this study was to identify alterations in the expression of oligodendrocyte precursor cell transcription factors in a mouse model of transient mild global hypoxia. Postnatal day (P) 7 mouse pups were exposed to hypoxia (7.5% O2) for 60minutes. We compared oligodendrocyte differentiation and subsequent myelin formation between hypoxia and sham animals at P9, P14 and P28 by examining the expression of key transcription factor regulators of oligodendrocyte differentiation (Ascl1, Olig1, Olig2, and Nkx2.2), as well as APC, a mature oligodendrocyte marker, in the major white matter regions including the corpus callosum, external capsule and anterior commissure. We also examined the effect on myelin formation by examining two myelin specific protein constituents, myelin associated glycoprotein (MAG) and myelin basic protein (MBP), in white matter tracts and whole brain lysate respectively. We found that transient hypoxia at P7 altered the expression of Ascl1, Olig1 and Nkx2.2, resulting in delayed myelination in the external capsule. In addition, our study showed that oligodendrocyte progenitor cells specified several days prior to a hypoxic event are more susceptible to maturation arrest than those specified shortly prior to hypoxia. Our results suggest that alterations of Ascl1, Olig1 and Nkx2.2 underlie impaired oligodendrocyte differentiation and deficient myelination in WMI. These transcription factors are potential therapeutic targets for the treatment of WMI in preterm infants.
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PMID:Region specific oligodendrocyte transcription factor expression in a model of neonatal hypoxic injury. 2854 87

Myelin, which is a multilamellar structure that sheathes the axon, is essential for normal neuronal function. In the central nervous system (CNS), myelin is produced by oligodendrocytes (OLs), which wrap their plasma membrane around axons. The dynamic membrane trafficking system, which relies on motor proteins, is required for myelin formation and maintenance. Previously, we reported that myosin ID (Myo1d) is distributed in rat CNS myelin and is especially enriched in the outer and inner cytoplasm-containing loops. Further, small interfering RNA (siRNA) treatment highlighted the involvement of Myo1d in the formation and maintenance of myelin in cultured OLs. Myo1d is one of the unconventional myosins, which may contribute to membrane dynamics, either in the wrapping process or transport of myelin membrane proteins during myelination. However, the function of Myo1d in myelin formation in vivo remains unclear. In the current study, to clarify the function of Myo1d in vivo, we surgically injected siRNA in the corpus callosum of a cuprizone-treated demyelination mouse model via stereotaxy. Knockdown of Myo1d expression in vivo decreased the intensities of myelin basic protein and myelin proteolipid protein immunofluorescence staining. However, neural/glial antigen 2-positive signals and adenomatous polyposis coli (APC/CC1)-positive cell numbers were unchanged by siRNA treatment. Furthermore, Myo1d knockdown treatment increased pro-inflammatory microglia and astrocytes during remyelination. In contrast, anti-inflammatory microglia were decreased. The percentage of caspase 3-positive cells in total CC1-positive OLs were also increased by Myo1d knockdown. These results indicated that Myo1d plays an important role during the regeneration process after demyelination.
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PMID:Unconventional Myosin ID is Involved in Remyelination After Cuprizone-Induced Demyelination. 2898 88


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