Vascular response to social cognitive performance measured by infrared thermography: A translational study from mouse to man.

To assess complex social recognition in mice, we previously developed the SocioBox paradigm. Unexpectedly, 4 weeks after performing in the SocioBox, mice displayed robust social avoidance during Y-maze sociability testing. This unique "sociophobia" acquisition could be documented in independent cohorts. We therefore employed infrared thermography as a non-invasive method of stress-monitoring during SocioBox testing (presentation of five other mice) versus empty box. A higher Centralization Index (body/tail temperature) in the SocioBox correlated negatively with social recognition memory and, after 4 weeks, with social preference in the Y-maze. Assuming that social stimuli might be associated with characteristic thermo-responses, we exposed healthy men (N = 103) with a comparably high intelligence level to a standardized test session including two cognitive tests with or without social component (face versus pattern recognition). In some analogy to the Centralization Index (within-subject measure) used in mice, the Reference Index (ratio nose/malar cheek temperature) was introduced to determine the autonomic facial response/flushing during social recognition testing. Whereas cognitive performance and salivary cortisol were comparable across human subjects and tests, the Face Recognition Test was associated with a characteristic Reference Index profile. Infrared thermography may have potential for discriminating disturbed social behaviors.

Correction to: Ketogenic diet ameliorates axonal defects and promotes myelination in Pelizaeus-Merzbacher disease.

The original article was published.

Ketogenic diet ameliorates axonal defects and promotes myelination in Pelizaeus-Merzbacher disease.

Pelizaeus-Merzbacher disease (PMD) is an untreatable and fatal leukodystrophy. In a model of PMD with perturbed blood-brain barrier integrity, cholesterol supplementation promotes myelin membrane growth. Here, we show that in contrast to the mouse model, dietary cholesterol in two PMD patients did not lead to a major advancement of hypomyelination, potentially because the intact blood-brain barrier precludes its entry into the CNS. We therefore turned to a PMD mouse model with preserved blood-brain barrier integrity and show that a high-fat/low-carbohydrate ketogenic diet restored oligodendrocyte integrity and increased CNS myelination. This dietary intervention also ameliorated axonal degeneration and normalized motor functions. Moreover, in a paradigm of adult remyelination, ketogenic diet facilitated repair and attenuated axon damage. We suggest that a therapy with lipids such as ketone bodies, that readily enter the brain, can circumvent the requirement of a disrupted blood-brain barrier in the treatment of myelin disease.

Fluorescent in situ hybridization of synaptic proteins imaged with super-resolution STED microscopy.

Super-resolution fluorescence microscopy is still a developing field. One of the limitations has been that standard labeling assays, which had been developed for conventional imaging, must be adjusted and optimized for each super-resolution method. These methods are more sensitive to noise, and require more intense labeling than conventional microscopy, which is not always trivial to achieve. Here, we describe the use of stimulation-emission depletion (STED) microscopy to locate messenger RNAs (mRNAs) in single neurons with high spatial precision. We address several technical difficulties we encountered in using fluorescent in situ hybridization (FISH) for STED imaging. We optimized the experimental protocol to detect mRNAs and proteins simultaneously, by performing FISH and immunostaining on the same samples. We tested our imaging approach in primary hippocampal neurons, studying the mRNAs of three important presynaptic proteins (synaptobrevin, synaptotagmin, and synaptophysin). Our approach allowed us to relate changes in mRNA levels and localization to neuronal physiology, under different activity regimes and also during neuronal development. We conclude that FISH can be performed efficiently using super-resolution techniques. This should contribute significantly to the clarification of the molecular mechanisms that govern mRNA distribution and dynamics within cells.