Biology subjects

Flachskamm, C.

Publications and source records attributed to Flachskamm, C..

4 recordsLinked to original sources

bioRxiv2025

Pharmacological Inhibition of FKBP51 Mitigates Early Life Adversity-Induced Social Deficits

Early life adversity (ELA) is a major risk factor for psychiatric disorders, but targeted preventative strategies are lacking due to poor mechanistic insight. The FKBP51 protein, a co-chaperone of the glucocorticoid receptor, is a key mediator of stress vulnerability. We tested if pharmacological inhibition of FKBP51 with the selective inhibitor SAFit2 prevents the long-term consequences of ELA. Mice exposed to ELA exhibited persistent deficits in social behavior, manifesting as social subordination in adolescence and adulthood. Early-life SAFit2 treatment fully rescued these ELA-induced behavioral impairments. Transcriptional profiling across six stress-relevant brain regions revealed that SAFit2 normalized ELA-driven gene expression changes, particularly in the medial prefrontal cortex and nucleus accumbens. Functional analysis showed the rescue converged on immunoregulatory and neuroactive ligand-receptor signaling pathways. Our findings establish FKBP51 as a critical pharmacological target for reversing the lasting impact of early life adversity on brain function, offering a path toward preventative treatment for ELA-related psychopathology.

neuroscience↗

bioRxiv2020

Sexually divergent effects of social dominance on chronic stress outcomes in mice

BackgroundSex and social context are two major factors in the development of depression and other stress-related disorders. However, few studies of the effects of stress on rodent behavior and physiology have investigated social context and fewer still have assessed the possibility of sex-specific effects of social context. MethodsWe assessed social dominance of group-living mice during several days of monitoring using a high-throughput automated behavioral tracking system. We then exposed groups from each sex to a three-week chronic mild stress (CMS) procedure, followed by a behavioral test battery. Finally, we used principle component analysis and post-hoc tests to explore the sources of variance in the behavioral outcome data. ResultsWe found stable hierarchies in both sexes, however social dominance in males exhibited several additional associations with behaviors related to locomotion and exploration that were not seen in females. Crucially, pre-stress social dominance status was associated with opposing outcomes on multiple behavioral readouts between the two sexes following CMS. In particular, subordinate male mice and dominant female mice appeared more responsive to the environmental challenge, as observed in anxiety-like and locomotor behaviors. ConclusionsThis work demonstrates that sex differences interact with preexisting social dominance status to alter the effects of chronic stress. It highlights the importance of understanding the interplay between sex and social context and its contribution to individual differences in stress response.

neuroscience↗

bioRxiv2019

Social context and dominance status contribute to sleep patterns and quality in groups of freely-moving mice

In many socially-living species, sleep patterns are subject to group influences, as individuals adjust to the presence, daily rhythms, and social pressures inherent to cohabitation. Disturbances in social functioning are comorbid with sleep problems in many prevalent psychiatric disorders, most notably, autism-spectrum, mood, and anxiety disorders (e.g., [1-3]). Our understanding of the common causality and the interplay between sleep impairment and psychiatric symptomatology could greatly benefit from experimental paradigms that allow simultaneous assessment of both domains of functioning. In laboratory mice, much is known about the sensitivity of sleep quality to a variety of experimental manipulations. Due to existing methodological restrictions, however, sleep studies are typically conducted in single-housed mice, thereby neglecting the influence of social dynamics and group-derived individual differences (however, see [4,5]). Here, we investigated sleep in a semi-naturalistic environment with freely-moving socially-housed groups of male mice using wireless electroencephalographic (EEG) monitoring devices and automated video tracking. In addition to multiple days of continuous behavioral data, we collected over fifty hours of EEG signal per mouse, recording simultaneously from all individuals in a group. We found evidence of in-group synchrony of sleep state patterns. Moreover, social status was a powerful predictor of sleep quality, such that sleep fragmentation, slow-wave sleep power, and rapid eye movement (REM) episode duration differed as a function of dominance status in the group. Finally, acute stress exposure had differential effects on REM sleep during recovery in dominant versus subordinate individuals. These findings highlight the importance of exploring sleep in a social context and are a step toward more informative research on the interplay between social functioning and sleep.

neuroscience↗

bioRxiv2018

Identity domains in complex behavior: Toward a biology of personality

Personality traits offer considerable insight into the biological basis of individual differences. However, existing approaches toward understanding personality across species rely on subjective criteria and limited sets of behavioral readouts, resulting in noisy and often inconsistent outcomes. Here, we introduce a mathematical framework for studying individual differences along dimensions with maximum consistency and discriminative power. We validate this framework in mice, using data from a system for high-throughput longitudinal monitoring of group-housed mice that yields a variety of readouts from all across an individuals behavioral repertoire. We describe a set of stable traits that capture variability in behavior and gene expression in the brain, allowing for better informed mechanistic investigations into the biology of individual differences.

animal behavior and cognition↗