The myth of brain damage: no change of neurofilament light chain during transient cognitive side-effects of ECT.

Electroconvulsive therapy (ECT) is an effective, safe, and mostly well-tolerated treatment for patients with severe or difficult to treat depression or psychotic disorders. However, a relevant number of patients experience subjective and/or objective cognitive side-effects. The mechanism of these transient deficits is not yet clear. Thus, our study prospectively investigated neurofilament light chain (NfL) concentrations as a highly sensitive biomarker for neuroaxonal damage along with cognitive performance during a course of ECT. Serum NfL concentrations from 15 patients with major depressive disorder receiving ECT were analyzed (1) 24 h before the first ECT, (2) 24 h and (3) 7 days after the last ECT (45 measurements in total). Neuropsychological testing including memory, executive functions and attention was performed at each time-point. NfL concentrations did not change between the three time-points, while a temporary cognitive impairment was found. Even in the subset of patients with the strongest impairment, NfL concentrations remained unchanged. Neuropsychological testing revealed the common pattern of transient cognitive side-effects with reduced performance 24 h post-ECT (global cognition score: p < 0.001; memory: p = 0.043; executive functions: p = 0.002) and return to baseline after 7 days (all p < 0.001). Our study adds to the evidence that neither ECT per se nor the transient cognitive side-effects seem to be associated with an increase of NfL as a marker of neuroaxonal damage. In contrast, we discuss cognitive side effects to be potentially interpreted as a byproduct of ECT's neuroplastic effects.

TfAP-2 is required for night sleep in Drosophila.

BACKGROUND: The AP-2 transcription factor APTF-1 is crucially required for developmentally controlled sleep behavior in Caenorhabditis elegans larvae. Its human ortholog, TFAP-2beta, causes Char disease and has also been linked to sleep disorders. These data suggest that AP-2 transcription factors may be highly conserved regulators of various types of sleep behavior. Here, we tested the idea that AP-2 controls adult sleep in Drosophila. RESULTS: Drosophila has one AP-2 ortholog called TfAP-2, which is essential for viability. To investigate its potential role in sleep behavior and neural development, we specifically downregulated TfAP-2 in the nervous system. We found that neuronal TfAP-2 knockdown almost completely abolished night sleep but did not affect day sleep. TfAP-2 insufficiency affected nervous system development. Conditional TfAP-2 knockdown in the adult also produced a modest sleep phenotype, suggesting that TfAP-2 acts both in larval as well as in differentiated neurons. CONCLUSIONS: Thus, our results show that AP-2 transcription factors are highly conserved regulators of development and sleep.

Structure predictions and interaction studies indicate homology of separase N-terminal regulatory domains and Drosophila THR.

The final resolution of sister chromatid cohesion during mitotic and meiotic divisions is mediated by activation of separase which cleaves a cohesin complex subunit. The structural basis of separase regulation is unknown. Separases from different eukaryotes share almost no sequence similarity, especially within the large N-terminal domain that precedes the protease domain except in Drosophila melanogaster. Moreover, sequence similarity among securin proteins, which associate as regulatory subunits with separase, is restricted to the signals that promote the mitotic degradation required for separase activation. Here, we address the surprising divergence of separase and securin sequences. The absence of an extended N-terminal separase domain in dipteran species is shown to be correlated with the expression of an extra regulatory subunit (THR). The interactions of THR with separase and securin in Drosophila melanogaster are analogous to those of the human N-terminal separase domain with its C-terminal domain and securin. Even heterologous interactions between Drosophila and human separase complex components occur in yeast two-hybrid experiments. Tertiary structure predictions reveal alpha-alpha superhelix folds in both THR and the N-terminal domains of nondipteran separases. The compatibility of these folds with a wide range of primary sequences has likely allowed the rapid divergence of THR/N-terminal separase sequences and securins, which contact this region.

Bällchen is required for self-renewal of germline stem cells in Drosophila melanogaster.

Self-renewing stem cells are pools of undifferentiated cells, which are maintained in cellular niche environments by distinct tissue-specific signalling pathways. In Drosophila melanogaster, female germline stem cells (GSCs) are maintained in a somatic niche of the gonads by BMP signalling. Here we report a novel function of the Drosophila kinase Bällchen (BALL), showing that its cell autonomous role is to maintain the self-renewing capacity of female GSCs independent of BMP signalling. ball mutant GSCs are eliminated from the niche and subsequently differentiate into mature eggs, indicating that BALL is largely dispensable for differentiation. Similar to female GSCs, BALL is required to maintain self-renewal of male GSCs, suggesting a tissue independent requirement of BALL for self-renewal of germline stem cells.