Biology subjects

Donegan, J. J.

Publications and source records attributed to Donegan, J. J..

2 recordsLinked to original sources

bioRxiv2026

Mitochondrial DNA copy number in neurodegenerative diseases: a global meta-analysis of 156 comparisons across 76 studies

Mitochondria are central hubs for cellular metabolism and mitochondrial dysfunction is a hallmark of many chronic diseases. Consequently, changes in mitochondrial DNA copy number (mtDNA-CN), the number of mtDNA genomes per cell or tissue sample, are associated with diseases ranging from cancer and obesity to psoriasis and all-cause mortality. MtDNA-CN especially holds promise as a biomarker for neurodegenerative diseases, but whether and how mtDNA-CN changes with neurodegeneration is controversial. Here, we performed a systematic review and meta-analysis of 76 studies including 156 comparisons of mtDNA-CN in populations with or without a neurodegenerative disease to identify overall trends and potential moderators that explain variation among studies. Overall, mtDNA-CN was not statistically different with neurodegeneration, but heterogeneity among studies was extreme (I2 = 99.5%). The diagnosed disease explained the most variation. For example, Alzheimer's patients showed a 21% decrease in mtDNA-CN, but there was no change in mtDNA-CN with Parkinson's disease. Decreases in mtDNA-CN during neurodegeneration were also more extreme at older ages. Surprisingly, the tissue sampled for mtDNA-CN was not particularly influential, except for certain diseases. Studies published in earlier years also showed more extreme decreases in mtDNA-CN with neurodegeneration. Excessive heterogeneity persisted even after accounting for all moderators and their interactions (I2 = 85.7%). We conclude that the general perception of decreased mtDNA-CN with neurodegeneration is a vast oversimplification that may stem from legacy effects of early studies. However, mtDNA levels offer great promise as biomarkers for neurodegeneration, other diseases, and general health metrics, assuming appropriate complications can be considered.

neuroscience↗

bioRxiv2020

Buprenorphine exposure alters the development and migration of interneurons in the cortex

The misuse of opioids has reached epidemic proportions over the last decade, with over 2.1 million people in the U.S. suffering from substance use disorders related to prescription opioid pain relievers. This increase in opioid misuse affects all demographics of society, including women of child-bearing age, which has led to a rise in opioid use during pregnancy. Opioid use during pregnancy has been associated with increased risk of obstetric complications and adverse neonatal outcomes, including neonatal abstinence syndrome. Currently, opioid use disorder in pregnant women is treated with long-acting opioid agonists, including buprenorphine. Although buprenorphine reduces illicit opioid use during pregnancy and improves infant outcomes at birth, few long-term studies of the neurodevelopmental consequences have been conducted. The goal of the current experiments was to examine the effects of buprenorphine on the development of the cortex using fetal brain tissue, 3D brain cultures, and rodent models. First, we demonstrated that we can grow cortical and subpallial spheroids, which model the cellular diversity, connectivity, and activity of the developing human brain. Next, we show that cells in the developing human cortex express the nociceptin opioid (NOP) receptor and that buprenorphine can signal through this receptor in cortical spheroids. Using subpallial spheroids to grow inhibitory interneurons, we show that buprenorphine can alter interneuron development and migration into the cortex. Finally, using a rodent model of prenatal buprenorphine exposure, we demonstrate that alterations in interneuron distribution can persist into adulthood. Together, these results suggest that more research is needed into the long-lasting consequences of buprenorphine exposure on the developing human brain.

developmental biology↗