Biology subjects

McDonough, I.

Publications and source records attributed to McDonough, I..

4 recordsLinked to original sources

bioRxiv2024

Adult choline supplementation in a Down syndrome model reduces co-morbidities and improves cognition

Down syndrome (DS) is the most common cause of early-onset Alzheimers disease (AD). Dietary choline has been proposed as a modifiable factor to improve cognitive and pathological outcomes of AD, especially as many do not reach adequate daily intake levels. Perinatal choline supplementation (Ch+) in the Ts65Dn mouse model of DS protects offspring against AD-relevant pathology and improves cognition, and dietary Ch+ in adult AD models also ameliorates pathology and improves cognition. However, dietary Ch+ in adult Ts65Dn mice has not yet been explored. To test whether Ch+ in adulthood improves DS co-morbidities, we fed trisomic Ts65Dn mice and disomic littermate controls with either choline normal (ChN; 1.1 g/kg) or Ch+ (5 g/kg) diets from 4.5-14 months of age. We found that Ch+ improved cognitive flexibility in a reverse place preference task and reduced weight gain and peripheral inflammation in female mice, whereas Ch+ improved glucose metabolism in male mice. In conclusion, we found that adulthood Ch+ benefits behavioral and biological factors important for general well-being in DS and related to AD risk.

neuroscience↗

bioRxiv2022

Dietary choline intake is necessary to prevent systems-wide organ pathology and reduce Alzheimers disease hallmarks

Evidence suggests that environmental factors may contribute to Alzheimers disease (AD). The B-like vitamin choline plays key roles in body- and brain-related functions. Choline produced endogenously by the phosphatidylethanolamine N-methyltransferase (PEMT) enzyme in the liver is not sufficient for adequate physiological functions, necessitating daily dietary intake. [~]90% of Americans dont reach the recommended daily choline intake. Thus, its imperative to determine whether dietary deficiency increases disease outcomes. Here, we placed 3xTg-AD, a model of AD, and non-transgenic (NonTg) control mice on either a sufficient choline (ChN) or choline deficient (Ch-; choline deficiency) diet from 3 to 12 (early to late adulthood) months of age. Ch- reduced plasma choline and acetylcholine levels, increased weight, and impaired both glucose metabolism and motor function in NonTg, with 3xTg-AD mice showing greater deficits. Tissue analyses showed cardiac and liver pathology, and elevated Amyloid-{beta} and phosphorylated tau in the hippocampus and cortex of 3xTg-AD Ch- mice. Unbiased proteomic analyses revealed Ch- altered hippocampal networks associated with microtubule function and postsynaptic membrane regulation. In plasma, Ch- altered protein networks associated with insulin metabolism, mitochondrial function, and inflammation. Collectively, our data highlight that dietary choline intake is necessary to prevent systems-wide organ pathology and reduce AD hallmark pathologies.

neuroscience↗

bioRxiv2018

The Relation Between White Matter Microstructure and Network Complexity: Implications for Processing Efficiency

Brain structure has been proposed to facilitate as well as constrain functional interactions within brain networks. Simulation models suggest that integrity of white matter (WM) microstructure should be positively related to the complexity of BOLD signal--a measure of network interactions. Using 121 young adults from the Human Connectome Project, we empirically tested whether greater WM integrity would be associated with greater complexity of the BOLD signal during rest via multiscale entropy. Multiscale entropy measures the lack of predictability within a given time series across varying time scales, thus being able to estimate fluctuating signal dynamics within brain networks. Using multivariate analysis techniques (Partial Least Squares), we found that greater WM integrity was associated with greater network complexity at fast time scales, but less network complexity at slower time scales. These findings implicate two separate pathways through which WM integrity affects brain function in the prefrontal cortex--an executive-prefrontal pathway and a perceptuo-occipital pathway. In two additional samples, the main patterns of WM and network complexity were replicated. These findings support simulation models of WM integrity and network complexity and provide new insights into brain structure-function relationships.

neuroscience↗

bioRxiv2016

Mindcontrol: A Web Application for Brain Segmentation Quality Control

Tissue classification plays a crucial role in the investigation of normal neural development, brain-behavior relationships, and the disease mechanisms of many psychiatric and neurological illnesses. Ensuring the accuracy of tissue classification is important for quality research and, in particular, the translation of imaging biomarkers to clinical practice. Assessment with the human eye is vital to correct various errors inherent to all currently available segmentation algorithms. Manual quality assurance becomes methodologically difficult at a large scale - a problem of increasing importance as the number of data sets is on the rise. To make this process more efficient, we have developed Mindcontrol, an open-source web application for the collaborative quality control of neuroimaging processing outputs. The Mindcontrol platform consists of a dashboard to organize data, descriptive visualizations to explore the data, an imaging viewer, and an in-browser annotation and editing toolbox for data curation and quality control. Mindcontrol is flexible and can be configured for the outputs of any software package in any data organization structure. Example configurations for three large, open-source datasets are presented: the 1000 Functional Connectomes Project (FCP), the Consortium for Reliability and Reproducibility (CoRR), and the Autism Brain Imaging Data Exchange (ABIDE) Collection. These demo applications link descriptive quality control metrics, regional brain volumes, and thickness scalars to a 3D imaging viewer and editing module, resulting in an easy-to-implement quality control protocol that can be scaled for any size and complexity of study.

bioinformatics↗