Biology subjects

Lowry, C. A.

Publications and source records attributed to Lowry, C. A..

4 recordsLinked to original sources

bioRxiv2026

Towards Identifying a Molecular Activator of Spreading Depolarization Generated by the Ischemic Brain

Spreading depolarizations (SDs) are waves of mass depolarization that propagate through gray matter following Na+/K+-ATPase (NKA) failure because of stroke, traumatic brain injury or sudden cardiac arrest. SDs expand the initial site of neuronal injury and worsen clinical outcomes. The molecular events underlying SD initiation and propagation are not well understood. In this rodent study, we hypothesized that gray matter stressed by oxygen/glucose deprivation (OGD) releases a compound(s) that promotes SD, which we term a spreading depolarization activator (SDa). We used rat brain slices incubated in artificial cerebrospinal fluid (aCSF) and subjected to OGD to release a putative SDa. The aCSF was collected either prior to ("Pre-SD aCSF") or 10 min after initiation of OGD conditions ("Post-SDOGD aCSF"). These solutions were then separately superfused over a healthy, naive (non-stressed) brain slice. Post-SDOGD aCSF (with re-normalized O2 and glucose) evoked SD in 82.35% of the naive brain slices (n = 17) whereas Pre-SD aCSF evoked no SD in 10 naive slices. Then to investigate the NKA as a potential target of the SDa, we used a hemolysis assay, comparing the effects of Pre- or Post-SDOGD aCSF on red blood cell (RBC) lysis and compared it to the known hemolytic effect of the NKA-specific inhibitor, palytoxin. Post-SDOGD aCSF evoked neither swelling nor lysis of RBCs on its own. However, when a sub-threshold concentration (0.01-0.02 nM) of the specific NKA inhibitor palytoxin (PLTX) was added, a striking "priming" effect was observed, whereby Post-SDOGD aCSF evoked a highly significant increase in both RBC swelling and then hemolysis, compared to Pre-SD aCSF. High pressure liquid chromatography (HPLC) experiments show a several-fold increase in released molecules post-SD vs pre-SD. Overall, this study provides support for SDa release capable of inducing SD-associated swelling in brain slices and, when combined with a trace amount of PLTX, swelling/hemolysis of RBCs caused by NKA inhibition. A greater understanding of the molecular events underlying SD should identify novel targets to reduce recurrent SD-evoked neuronal injury under ischemic conditions.

neuroscience↗

bioRxiv2023

Association of homelessness and diet on the gut microbiome: A United States-Veteran Microbiome Project (US-VMP) study

Military Veterans account for 8% of homeless individuals living in the United States. To highlight associations between history of homelessness and the gut microbiome, we compared the gut microbiome of Veterans who reported having a previous experience of homelessness to those from individuals who reported never having experienced a period of homelessness. Moreover, we examined the impact of the cumulative exposure of prior and current homelessness to understand possible associations between these experiences and the gut microbiome. Microbiome samples underwent genomic sequencing and were analyzed based on alpha diversity, beta diversity, and taxonomic differences. Additionally, demographic information, dietary data, and mental health history were collected. A lifetime history of homelessness was found to be associated with alcohol use disorder, substance use disorder, and healthy eating index compared to those without such a history. In terms of differences in gut microbiota, beta diversity was significantly different between Veterans that had experienced homelessness and Veterans that had never been homeless (p = 0.047, Weighted UniFrac), while alpha diversity was similar. The microbial community differences were, in part, driven by a lower relative abundance of Akkermansia in Veterans that had experienced homelessness (mean {+/-} SD; 1.07 {+/-} 3.85) compared to Veterans that had never been homeless (2.02 {+/-} 5.36) (p = 0.014, ancom-bc2). Additional research is required to facilitate understanding regarding complex associations between homelessness, the gut microbiome, and mental and physical health conditions, with a focus on increasing understanding regarding the longitudinal impact of housing instability throughout the lifespan. ImportanceAlthough there are known stressors related to homelessness, as well as chronic health conditions experienced by those without stable housing, there has been limited work evaluating the associations between microbial community composition and homelessness. We analyzed, for the first time, bacterial gut microbiome associations among those with experiences of homelessness on alpha diversity, beta diversity, and taxonomic differences. Additionally, we characterized the influences of diet, demographic characteristics, military service history and mental health conditions on the microbiome of Veterans with and without any lifetime history of homelessness. Future longitudinal research to evaluate the complex relationships between homelessness, the gut microbiome, and mental health outcomes is recommended. Ultimately, differences in the gut microbiome of individuals experiencing and not experiencing homelessness could assist in identification of treatment targets to improve health outcomes.

microbiology↗

bioRxiv2021

Probiotic bacteria and bile acid profile are modulated by prebiotic diet and associate with facilitated diurnal clock/sleep realignment after chronic disruption of rhythms

Chronic disruption of rhythms (CDR) impacts sleep and can result in circadian misalignment of physiological systems, which in turn is associated with increased disease risk. Exposure to repeated or severe stressors also disturbs sleep and diurnal rhythms. Prebiotic nutrients produce favorable changes in gut microbial ecology, the gut metabolome, and reduce several negative impacts of acute severe stressor exposure, including disturbed sleep, core body temperature rhythmicity, and gut microbial dysbiosis. This study tested the hypothesis whether prebiotics can also reduce the negative impacts of CDR by facilitating light/dark realignment of sleep/wake, core body temperature, and locomotor activity; and whether prebiotic-induced changes in bacteria and bile acid profiles are associated with these effects. Male, Sprague Dawley rats were fed diets enriched in prebiotic substrates or calorically matched control chow. After 5 weeks on diet, rats were exposed to CDR (12h light/dark reversal, weekly for 8 weeks) or remained on undisturbed normal light/dark cycles (NLD). Sleep EEG, core body temperature, and locomotor activity were recorded via biotelemetry in freely moving rats. Fecal samples were collected on experimental days -33, 0 (day of onset of CDR), and 42. Taxonomic identification and relative abundances of gut microbes were measured in fecal samples using 16S rRNA gene sequencing and shotgun metagenomics. Fecal primary, bacterially-modified secondary, and conjugated bile acids were measured using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Prebiotic diet produced rapid and stable increases in the relative abundances of Parabacteroides distasonis and Ruminiclostridium 5. Shotgun metagenomics analyses confirmed reliable increases in relative abundances of Parabacteroides distasonis and Clostridium leptum, a member of the Ruminiclostridium genus. Prebiotic diet also modified fecal bile acid profiles; and based on correlational and step-wise regression analyses, Parabacteroides distasonis and Ruminiclostridium 5 were positively associated with each other and negatively associated with secondary and conjugated bile acids. Prebiotic diet, but not CDR, impacted beta diversity. Measures of alpha diversity evenness were decreased by CDR and prebiotic diet prevented that effect. Rats exposed to CDR while eating prebiotic, compared to control diet, more quickly realigned NREM sleep and core body temperature (ClockLab) diurnal rhythms to the altered light/dark cycle. Finally, both cholic acid and Ruminiclostridium 5 prior to CDR were associated with time to realign CBT rhythms to the new light/dark cycle after CDR; whereas both Ruminiclostridium 5 and taurocholic acid prior to CDR were associated with NREM sleep recovery after CDR. These results suggest that ingestion of prebiotic substrates is an effective strategy to increase the relative abundance of health promoting microbes, alter the fecal bile acid profile, and facilitate the recovery and realignment of sleep and diurnal rhythms after circadian disruption.

physiology↗

bioRxiv2020

Immunization with Mycobacterium vaccae NCTC 11659 prevents the development of PTSD- like sleep and behavioral phenotypes after sleep disruption and acute stress in mice

Because regular sleep disruption can increase vulnerability to stress-related psychiatric disorders, there is a need to explore novel countermeasures to increase stress resilience after inadequate sleep. In this study, we explored the impact of 5 days of intermittent sleep disruption on vulnerability to acute social defeat stress in mice, and investigated the ability of the environmental, immunomodulatory bacterium Mycobacterium vaccae NCTC 11659 (MV) to promote stress resilience in that context. We found that mice receiving sleep disruption plus acute stress developed sleep and behavioral phenotypes that had some features of human posttraumatic stress disorder (PTSD) including reduced NREM delta power and increased NREM beta power in post-stress sleep EEG, persistent increases in sleep fragmentation and the REM:Sleep ratio, and behavioral changes. Importantly, immunization with heat-killed MV prevented the development of this phenotype. These results support further research into novel, microbial-based countermeasures to improve health and increase resilience to sleep disruption.

neuroscience↗