Editorial: epilepsy and neurodevelopmental diseases

The association between epilepsy and neurodevelopmental diseases is well-recognized and has gained significant attention in the field of neuroscience in recent years. One of the main reasons for this interest is the need for a better understanding of the events that lead to the development and maturation of the CNS. This is a fundamental and necessary basis for potential breakthrough strategies that could guide novel and more effective disease-modifying therapeutic approaches to neurodevelopmental syndromes that are frequently characterized by severe and drug-resistant epilepsy. The perspective of such new therapeutic strategies is very promising. At the state-of-theart, patients afflicted by these rare neurodevelopmental disorders mostly rely on “symptomatic” approaches that mitigate seizures and other major symptoms but do not target the underlying biological causes of the disease. The study of this vast field of research is extremely complex and requires a multidisciplinary approach, from neuropathological to molecular and functional studies since even “simple” triggering events (e.g., a genetic mutation) during critical periods of brain development can lead to widespread effects on brain morphological and functional features

LINC00507 Is Specifically Expressed in the Primate Cortex and Has Age-Dependent Expression Patterns

Over the past decade, there has been an increase in the appreciation of the role of non-coding RNA in the development of organism phenotype. It is possible to divide the non-coding elements of the transcriptome into three categories: short non-coding RNAs, circular RNAs and long non-coding RNAs. Long non-coding RNAs are those transcripts that are greater than 200 nts in length and lack any significant open reading frames that produce proteins greater then 100 amino acids. Long intervening non-coding RNAs (lincRNAs) are a subclass of long non-coding RNAs. In contrast to protein coding RNAs, lincRNAs are expressed in a more tissue- and species-specific manner. In particular, many lincRNAs are only conserved amongst higher primates. This coupled with the propensity of many lincRNAs to be expressed in the brain, suggests that they are in fact one of the major drivers of organism complexity. We analysed 39 lincRNAs that are expressed in the frontal cortex and identified LINC00507 as being expressed in a cortex-specific manner in non-human primates and humans. The expression patterns of LINC00507 appear to be age-dependent, suggesting it may be involved in brain development of higher primates. Moreover, the analysis of LINC00507 potential to bind ribosomes revealed that this previously identified non-coding transcript may harbour a micropeptide

Calcineurin controls expression of EAAT1/GLAST in mouse and human cultured astrocytes through dynamic regulation of protein synthesis and degradation

Alterations in the expression of glutamate/aspartate transporter (GLAST) have been associated with several neuropathological conditions including Alzheimer\u2019s disease and epilepsy. However, the mechanisms by which GLAST expression is altered are poorly understood. Here we used a combination of pharmacological and genetic approaches coupled with quantitative PCR and Western blot to investigate the mechanism of the regulation of GLAST expression by a Ca2+ /calmodulin-activated phosphatase calcineurin (CaN). We show that treatment of cultured hippocampal mouse and fetal human astrocytes with a CaN inhibitor FK506 resulted in a dynamic modulation of GLAST protein expression, being downregulated after 24\u201348 h, but upregulated after 7 days of continuous FK506 (200 nM) treatment. Protein synthesis, as assessed by puromycin incorporation in neo-synthesized polypeptides, was inhibited already after 1 h of FK506 treatment, while the use of a proteasome inhibitor MG132 (1 \ub5M) shows that GLAST protein degradation was only suppressed after 7 days of FK506 treatment. In astrocytes with constitutive genetic ablation of CaN both protein synthesis and degradation were significantly inhibited. Taken together, our data suggest that, in cultured astrocytes, CaN controls GLAST expression at a posttranscriptional level through regulation of GLAST protein synthesis and degradation

K-Band Observations of Boxy Bulges. I. Morphology and Surface Brightness Profiles

Kn-band images, unsharp-masked images, as well as major-axis and vertically- summed surface brightness profiles are presented for 30 edge-on spiral galaxies, most with a boxy or peanut-shaped (B/PS) bulge. Such galaxies have more complex morphologies than galaxies of other bulge types, more often showing (off-)centered X structures, secondary major-axis maxima and spiral-like structures. Those features are also observed in N-body simulations of barred discs and may trace the main bar orbit families. The surface brightness profiles of galaxies with a B/PS bulge are also more complex, with typically 3 or more clearly separated regions, including a flat intermediate region (Freeman Type II profiles). Those radial breaks offer evidence for bar-driven transfer of angular momentum and radial redistribution of material. The profiles also suggest a rapid variation of the scaleheight of the disc material, contrary to conventional wisdom but again as expected from vertical resonances and instabilities in barred discs. The steep inner region of the surface brightness profiles is often shorter than the isophotally thick part of the galaxies, itself always shorter than the flat region of the profiles. Contrary to the standard `bulge + disc' model, we thus propose that galaxies with a B/PS bulge are composed of a thin concentrated disc (a disc-like bulge) contained within a partially thick bar (the B/PS bulge) and a thin outer disc. The inner disc likely formed secularly through bar-driven processes and is responsible for the steep inner region of the surface brightness profiles, while the bar is responsible for the flat region and the thick complex morphological structures observed. Those components are strongly coupled dynamically and are formed mostly of the same (disc) material. [Abridged]Comment: 23 pages, 34 figures. Accepted for publication in MNRAS. A version with full resolution figures is available at http://www-astro.physics.ox.ac.uk/~bureau/pub_list.htm