Biology subjects

McDonald, E.

Publications and source records attributed to McDonald, E..

3 recordsLinked to original sources

bioRxiv2025

Adolescent alcohol consumption alters sex-specific behaviors associated with prefrontal functional connectivity in mice

The prefrontal cortex (PFC) is one of the last brain regions to fully mature, making it particularly sensitive to drug use early in life. Both human and rodent studies find long-lasting behavioral changes after adolescent alcohol exposure that implicate underlying disruptions in PFC development, including structural abnormalities and altered brain functional connectivity. Few rodent studies have been conducted to understand the network-level implications of these disruptions. We assessed how adolescent binge-like alcohol consumption in a drinking in the dark (DID) model affected adult alcohol consumption, behavioral exploration, and brain-wide functional connectivity in mice. Approximately one month after the conclusion of DID, only female mice exposed to alcohol during adolescence exhibited aversion-resistant alcohol preference in adulthood. Adult females exhibited additional sex-specific changes in exploratory behavior in the elevated plus maze after adolescent alcohol consumption. Resting state neuroimaging revealed sex-specific changes in prefrontal cortical connections with sensory motor, hippocampal, striatal, and other networks, providing insights into the putative systems underlying deficits caused by adolescent alcohol exposure. Critically, our data corroborate a growing body of literature in human and rodent studies demonstrating that adolescent alcohol use may increase risk for adult alcohol use more strongly in females. Finally, we identify neural correlates of this effect that include both known and novel neural networks and tie these back to human datasets, allowing biological and mechanistic targets to be further explored for future study and interventions.

neuroscience↗

bioRxiv2025

The 1-Cys peroxiredoxin, PRDX-6, suppresses a pro-survival response, including the Flavin monoxygenase, FMO-2, that protects against fungal and bacterial infection

Reactive oxygen species (ROS)-induced cell damage contributes to many diseases. However, ROS also contribute to cell signaling and immune defences. As ubiquitous thiol peroxidases, peroxiredoxins (Prdx) play integral roles in balancing ROS functions. High levels of Prdx6 are associated with increased metastasis and resistance to chemotherapy, rendering Prdx6 a therapeutic target for treatment of a broad range of cancers. However, Prdx6, has additional activities, in lipid signalling and selenocysteine metabolism, and it remains unclear how Prdx6s thiol peroxidase activity contributes to disease or ageing. Here we have investigated the role/s of Prdx6 in the stress responses and ageing of the nematode worm Caenorhabditis. elegans. Unexpectedly, we have found that C. elegans lacking prdx-6, have an increased resistance to oxidative stress and extended lifespan under some conditions. Moreover, prdx-6 mutant worms are also more resistant to infection with two opportunistic human pathogens; the gram-positive bacteria Staphylococcus aureus and the dimorphic yeast Candida albicans. Our data suggest that increased ROS levels in prdx-6 mutant worms lead to increased cell death in the germ line, and increased expression of the Flavin monooxygenase, FMO-2 in other tissues. FMO-2 has a conserved pro-survival function and is upregulated by the NHR-49(PPAR/HNF4) transcriptional regulator in response to various stresses, including peroxides and S. aureus infection. Here we reveal that fmo-2 expression is also increased as an NHR-49-dependent protective response to C. albicans. Thus, in addition to its anti-ageing role, FMO-2 protects C. elegans against both fungal and bacterial infections. Accordingly, we propose that elevated fmo-2 expression contributes to the increased stress resistance, lifespan and innate immunity of prdx-6 mutant animals. These findings further illustrate the complex roles that ROS/PRDX can play in stress resistance, immunity and ageing. HighlightsO_LIPRDX-6 is expressed in specific interneurons and intestine C_LIO_LILoss of PRDX-6 increases germ cell apoptosis C_LIO_LILoss of PRDX-6 increases C. elegans stress resistance, innate immunity and longevity C_LIO_LILoss of PRDX-6 and infection increase expression of the flavin monooxygenase fmo-2 C_LIO_LIFMO-2 protects against infection with the fungal pathogen Candida albicans C_LI

immunology↗

bioRxiv2022

Wavelet-based Approach for Diagnosing Attention Deficit Hyperactivity Disorder (ADHD)

Attention deficit hyperactivity disorder (ADHD) is a common cognitive disorder affecting children. ADHD can interfere with educational, social, and emotional development, so early detection is essential for obtaining proper care. Standard ADHD diagnostic protocols rely heavily on subjective assessments of perceived behavior. An objective diagnostic measure would be a welcome development and potentially aid in accurately and efficiently diagnosing ADHD. Analysis of pupillary dynamics has been proposed as a promising alternative method of detecting affected individuals effectively. This study proposes a method based on the self-similarity of pupillary dynamics and assesses its strength as a potential diagnostic biomarker. Localized discriminatory features are developed in the wavelet domain and selected via a rolling window method to build classifiers. The application on a task-based pupil diameter time series dataset of children aged 10-12 years shows that the proposed method achieves greater than 78% accuracy in detecting ADHD. Comparing with a recent approach that constructs features in the original data domain, the proposed wavelet-based classifier achieves more accurate ADHD classification with fewer features. The findings suggest that the proposed diagnostic procedure involving interpretable wavelet-based self-similarity features of pupil diameter data can potentially aid in improving the efficacy of ADHD diagnosis.

bioinformatics↗