Biology subjects

Elliott, J. E.

Publications and source records attributed to Elliott, J. E..

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↗

bioRxiv2024

Heart rate variability impairment during sleep in Veterans with REM sleep behavior disorder, traumatic brain injury, and posttraumatic stress disorder: An early potential window into autonomic dysfunction?

Individuals with comorbid REM sleep behavior disorder (RBD) and neurotrauma (defined by traumatic brain injury and post-traumatic stress disorder) have an earlier age of RBD symptom onset, increased RBD-related symptom severity and more neurological features indicative of prodromal synucleinopathy compared to RBD only. An early sign of neurodegenerative condition is autonomic dysfunction, which we sought to evaluate by examining heart rate variability during sleep. Participants with overnight polysomnography were recruited from the VA Portland Health Care System. Veterans without neurotrauma or RBD (controls; n=19), with RBD only (RBD, n=14), and with RBD and neurotrauma (RBD+NT, n=19) were evaluated. Eligible 5-minute NREM and REM epochs without apneas/hypopneas, microarousals, and ectopic beats were analyzed for frequency and time domain (e.g. low frequency power, LF; high frequency power, HF; root mean square of successive RR intervals, RMSSD; % of RR intervals that vary [≥]50 ms, pNN50) heart rate variability outcomes. Heart rate did not significantly differ between groups in any sleep stage. Time domain and frequency domain variables (e.g., LF power, HF power, RMSSD, and pNN50) were significantly reduced in the RBD and RBD+NT groups compared to controls and RBD only during NREM sleep. There were no group differences detected during REM sleep. These data suggest significant reductions in heart rate variability during NREM sleep in RBD+NT participants, suggesting greater autonomic dysfunction compared to controls or RBD alone. Heart rate variability during sleep may be an early, promising biomarker, yielding mechanistic insight for diagnosis and prognosis of early neurodegeneration in this vulnerable population. STATEMENT OF SIGNIFICANCEComorbid REM sleep behavior disorder (RBD) and neurotrauma (NT, traumatic brain injury + post-traumatic stress disorder; RBD+NT) is associated with increased neurodegenerative symptom burden and worsened health. Sleep and autonomic function are integrally and bidirectionally related to neurodegenerative processes. In the current study, we sought to determine if early signs of autonomic dysfunction, measured via heart rate variability (HRV), were present during sleep in comorbid RBD+NT compared to RBD only and controls. Our data show reduced time and frequency domain HRV during NREM sleep in RBD+NT Veterans compared to RBD only and controls. These data contribute evidence that participants with RBD and comorbid NT demonstrate significantly worse autonomic dysfunction compared to age/sex matched participants with RBD alone.

physiology↗

bioRxiv2024

Aquaporin-4 mis-localization slows glymphatic clearance of α-synuclein and promotes α-synuclein pathology and aggregate propagation

The appearance of misfolded and aggregated proteins is a pathological hallmark of numerous neurodegenerative diseases including Alzheimers disease and Parkinsons disease. Sleep disruption is proposed to contribute to these pathological processes and is a common early feature among neurodegenerative disorders. Synucleinopathies are a subclass of neurodegenerative conditions defined by the presence of -synuclein aggregates, which may not only enhance cell death, but also contribute to disease progression by seeding the formation of additional aggregates in neighboring cells. The mechanisms driving intercellular transmission of aggregates remains unclear. We propose that disruption of sleep-active glymphatic function, caused by loss of precise perivascular AQP4 localization, inhibits -synuclein clearance and facilitates -synuclein propagation and seeding. We examined human post-mortem frontal cortex and found that neocortical -synuclein pathology was associated with AQP4 mis-localization throughout the gray matter. Using a transgenic mouse model lacking the adapter protein -syntrophin, we observed that loss of perivascular AQP4 localization impairs the glymphatic clearance of -synuclein from intersititial to cerebrospinal fluid. Using a mouse model of -synuclein propogation, using pre-formed fibril injection, we observed that loss of perivascular AQP4 localization increased -synuclein aggregates. Our results indicate -synuclein clearance and propagation are mediated by glymphatic function and that AQP4 mis-localization observed in the presence of human synucleinopathy may contribute to the development and propagation of Lewy body pathology in conditions such as Lewy Body Dementia and Parkinsons disease. SummaryIn a human postmortem case series, we observe that neocortical Lewy body pathology is associated with mis-localization of the astroglial water channel aquaporin-4 (AQP4). In mice, -synuclein is cleared from the brain along perivascular pathways, while loss of perivascular AQP4 localization impairs glymphatic -synuclein clearance to the CSF. Furthermore, loss of perivascular AQP4 localization promotes the development and propagation of -synuclein aggregates.

neuroscience↗