Biology subjects

Potter, Z.

Publications and source records attributed to Potter, Z..

3 recordsLinked to original sources

bioRxiv2026

Temporal Trajectories of Motor and Cognitive Dysfunction After Combined PTSD and TBI in Mice: Implications for Neurodegenerative Disease Vulnerability

Post-Traumatic Stress Disorder (PTSD) commonly occurs alongside Traumatic Brain Injury (TBI), yet the chronic behavioral consequences of combined neurotrauma (i.e., PTSD and TBI) across the sexes remain unclear. Using a mouse model combining Single Prolonged Stress (SPS) as a model for PTSD and Controlled Cortical Impact (CCI) as a model for TBI, we assessed gait, anxiety-like behavior, and contextual fear learning and extinction at 2, 4, and 12-weeks post-injury. Combined neurotrauma produced early and persistent gait impairments in both sexes, delayed changes to anxiety-like behavior characterized by reduced avoidance of an anxiogenic environment, and long-lasting contextual fear recall deficits. Impaired learning was observed in males, where they demonstrated reduced fear acquisition and diminished extinction rates at later time points while females showed no deficits. Across testing and sex, peak deficits emerged at 4 weeks post-neurotrauma. Together, these findings define a sex- and time-dependent behavioral phenotype following combined neurotrauma and underscore the importance of modeling comorbidity to capture the temporal and neurobehavioral consequences of trauma exposure that more closely reflect clinical populations.

animal behavior and cognition↗

bioRxiv2025

Centella asiatica improves sleep quality and quantity in aged mice

Age-related sleep disruption is common in older adults. Not only does the total amount of time spent in sleep decline, but the number of arousals during sleep increases with age. As sleep is important for both memory consolidation and to prevent neurodegenerative pathology, this decline in sleep and/or sleep consolidation may underlie age-related cognitive decline and dementias. Furthermore, treatment of sleep disruption can improve quality of life. However, few interventions have successfully reversed age-related sleep decline. Extracts from the plant Centella asiatica have demonstrated neuroprotective effects in human, rodent, and fly models of aging and neurodegenerative diseases, and is a promising intervention for dementias, yet little is known about how these extracts affect sleep patterns. Here, we administered Centella asiatica water extract (CAW) dosed or control chow to male and female C57BL6/J mice aged 18 months. Effects on sleep composition were determined using electrodes that recorded EEG and EMG signals. We found that CAW dosed chow (1000 mg/kg/day) increased REM sleep time in aged male mice and decreased the number of arousals during sleep observed in aged females, compared to age- and sex-matched controls. We conclude that CAW administered in food has a moderate, sex-dependent effect on sleep quantity and quality. Statement of SignificanceSleep declines with age and may underline age-related cognitive changes. However, few interventions have successfully reversed age-related sleep and cognitive decline. This study found that botanical extract from the plant Centella asiatica increased total REM sleep time in aged male mice, and decreased sleep fragmentation in aged female mice, compared to age- and sex-matched controls. Whether these moderate, sex-dependent effect sizes on sleep in aged mice are impactful enough to affect cognition, quality of life, and/or neurodegenerative pathology could be explored in future studies.

neuroscience↗

bioRxiv2021

Profiling of the drug resistance of thousands of Src tyrosine kinase mutants uncovers a regulatory network that couples autoinhibition to the dynamics of the catalytic domain

Kinase inhibitors are effective cancer therapies but resistance often limits clinical efficacy. Despite the cataloguing of numerous resistance mutations, our understanding of kinase inhibitor resistance is still incomplete. Here, we comprehensively profiled the resistance of [~]3500 Src tyrosine kinase mutants to four different ATP-competitive inhibitors. We found that ATP-competitive inhibitor resistance mutations are distributed throughout Srcs catalytic domain. In addition to inhibitor contact residues, residues that participate in regulating Srcs phosphotransferase activity were prone to the development of resistance. Unexpectedly, we found that a resistance-prone cluster of residues located on the top face of the N-terminal lobe of Srcs catalytic domain contributes to autoinhibition by reducing catalytic domain dynamics, and mutations in this cluster led to resistance by lowering inhibitor affinity and promoting kinase hyperactivation. Together, our studies demonstrate how drug resistance profiling can be used to define potential resistance pathways and uncover new mechanisms of kinase regulation.

biochemistry↗