Genetically induced brain inflammation by Cnp deletion transiently benefits from microglia depletion.

Reduced expression of 2'-3'-cyclic nucleotide 3'-phosphodiesterase (Cnp) in humans and mice causes white matter inflammation and catatonic signs. These consequences are experimentally alleviated by microglia ablation via colony-stimulating factor 1 receptor (CSF1R) inhibition using PLX5622. Here we address for the first time preclinical topics crucial for translation, most importantly 1) the comparison of 2 long-term PLX5622 applications (prevention and treatment) vs. 1 treatment alone, 2) the correlation of catatonic signs and executive dysfunction, 3) the phenotype of leftover microglia evading depletion, and 4) the role of intercellular interactions for efficient CSF1R inhibition. Based on our Cnp-/- mouse model and in vitro time-lapse imaging, we report the unexpected discovery that microglia surviving under PLX5622 display a highly inflammatory phenotype including aggressive premortal phagocytosis of oligodendrocyte precursor cells. Interestingly, ablating microglia in vitro requires mixed glial cultures, whereas cultured pure microglia withstand PLX5622 application. Importantly, 2 extended rounds of CSF1R inhibition are not superior to 1 treatment regarding any readout investigated (magnetic resonance imaging and magnetic resonance spectroscopy, behavior, immunohistochemistry). Catatonia-related executive dysfunction and brain atrophy of Cnp-/- mice fail to improve under PLX5622. To conclude, even though microglia depletion is temporarily beneficial and worth pursuing, complementary treatment strategies are needed for full and lasting recovery.-Fernandez Garcia-Agudo, L., Janova, H., Sendler, L. E., Arinrad, S., Steixner, A. A., Hassouna, I., Balmuth, E., Ronnenberg, A., Schopf, N., van der Flier, F. J., Begemann, M., Martens, H., Weber, M. S., Boretius, S., Nave, K.-A., Ehrenreich, H. Genetically induced brain inflammation by Cnp deletion transiently benefits from microglia depletion.

Musical meaning modulates word acquisition.

Musical excerpts have been shown to have the capacity to prime the processing of target words and vice versa, strongly suggesting that music can convey concepts. However, to date no study has investigated an influence of musical semantics on novel word acquisition, thus corroborating evidence for a similarity of underlying semantic processing of music and words behaviourally. The current study investigates whether semantic content of music can assist the acquisition of novel words. Forty novel words and their German translation were visually presented to 26 participants accompanied by either semantically congruent or incongruent music. Semantic congruence between music and words was expected to increase performance in the subsequent forced-choice recognition test. Participants performed significantly better on the retention of novel words presented with semantically congruent music compared to those presented with semantically incongruent music. This provides first evidence that semantic "enrichment" by music during novel word learning can augment novel word acquisition. This finding may lead to novel approaches in foreign language acquisition and language rehabilitation, and further strongly supports the concept that music has a strong capacity to iconically convey meaning.

Losing track of time through delayed body representations.

The ability to keep track of time is perceived as crucial in most human societies. However, to lose track of time may also serve an important social role, associated with recreational purpose. To this end a number of social technologies are employed, some of which may relate to a manipulation of time perception through a modulation of body representation. Here, we investigated an influence of real-time or delayed videos of own-body representations on time perception in an experimental setup with virtual mirrors. Seventy participants were asked to either stay in the installation until they thought that a defined time (90 s) had passed, or they were encouraged to stay in the installation as long as they wanted and after exiting were asked to estimate the duration of their stay. Results show that a modulation of body representation by time-delayed representations of the mirror-video displays influenced time perception. Furthermore, these time-delayed conditions were associated with a greater sense of arousal and intoxication. We suggest that feeding in references to the immediate past into working memory could be the underlying mental mechanism mediating the observed modulation of time perception. We argue that such an influence on time perception would probably not only be achieved visually, but might also work with acoustic references to the immediate past (e.g., with music).