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Archive for the ‘Myelin’ Category

“sintinaptoo” is a nonword that makes it hard to read nonwords

Posted in CNTNAP2, FOXP2, Myelin, Superior temporal cortex, tagged , , , , on November 7, 2008| Leave a Comment »

Day 191 - Stick it Out

Image by lintmachine via Flickr

Like “Joe the Plumber” (whose real name is Samuel), CNTNAP2 (whose real name is CASPR2) has achieved a bit of fame lately.  While recently appearing almost everywhere (here, here, here) except FOX News, CNTNAP2 (not Joe the Plumber) is apparently a transcriptional target of the infamous FOXP2 “language gene” – so says Sonja C. Vernes & colleagues [doi: 10.1056/NEJMoa0802828] who precipitated DNA-protein complexes using anti-FOXP2 antibodies from a cell line transiently expressing FOXP2. The team later evaluated measures of expressive and receptive language abilities and nonsense-word repetition and found that a series of snps – most significantly rs17236239 – were associated with performance of children from a consortium of families at risk for language impairment.  This adds to several previous reports of CNTNAP2 and risk for autism, a disorder where language ability is severely impaired.

So what’s all the fuss ? How can something so insignificant (rs17236239 not Joe the Plumber) stir up so much trouble ?  Well, as reported in a previous post, the expression of CNTNAP2 in the developing superior temporal cortex may be a relevant clue since this brain region is activated by language tasks.  Also, this gene encodes a rather massive protein which (as reported by Coman et al.,) seems to participate in the establishment of myelination and “nodes” that permit rapid neural transmission and long-range coordination across neural structures in the brain. Interestingly, this gene shows evidence for recent positive selection in humans (as posted on here and here) although the newly derived G-allele at rs17236239 seems to be the allele that is causing the language difficulties.  My own 23andMe profile shows a middling A/G here which makes it slightly hard to recall and repeat “Samuel Wurzelbacher”.

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Epigenetic keys to brain repair

Posted in HDACs, Myelin, tagged , on July 10, 2008| Leave a Comment »

TATA-binding protein (TBP) recognizes TATA seq...Image via Wikipedia Siming Shen et al., in their paper, “Age-dependent epigenetic control of differentiation inhibitors is critical for remyelination efficiency“ provide insight on basic mechanisms of myelination. While myelination (think of it as the plastic insulation on copper electrical wires) makes normally developing neural networks much more efficient, it has a way of inhibiting the re-development and repair of mature neural circuits. The research team shows that recruitment of histone deacetylases (HDACs) is rather inefficient in mature oligodendrocytes precursor cells (the cells that adhere to bare neuronal axons and form the insulating myelin-rich sheath) in contrast to younger cells which differentiate readily. HDAC1 and HDAC2 are shown to down-regulate of Hes5 and Sox2, which have previously been implicated in blocking the differentiation of stem cells to oligodendrocytes. Here, the term ‘epigenetic’ refers to the mechanism of gene regulation – not by way of transcription factors binding to specific sequences – but rather, by factors being sterically blocked from binding by the 3-dimensional superstructure of the chromosome that occurs when histone proteins are deacetylated. The team suggests that as the brain ages, it becomes more difficult to recruit HDAC1,2 to the promoters needed to shut down the expression of the differentiation inhibitors. The results pose a confound for the certain applications of inhibitors of histone deacetylases (HDACi) which have demonstrated anti-tumor activity – but may – as suggested by this article – have negative consequences on brain repair processes.

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