Biology subjects

Damschroder, D.

Publications and source records attributed to Damschroder, D..

4 recordsLinked to original sources

bioRxiv2025

Changes in cell size occur across brain regions in the aging Drosophila brain.

Aging is accompanied by complex cellular changes in the brain, yet alterations in cell size and brain volume during early adulthood remain poorly characterized. We used flow cytometry to examine cell size in the aging Drosophila melanogaster brain across genotypes, sexes, and brain regions, comparing the optic lobes (OL) and central brain (CB). We found substantial heterogeneity in brain cell sizes accompanied by a significant decrease in average cell sizes with age across genotypes, sexes, and regions. This reduction emerged early in adulthood and occurred in both the OL and CB, although the OL contained smaller cells than the CB. In parallel, we detected significant age-dependent accumulation of polyploid cells, defined as cells with a greater than 2C DNA content. Although polyploid cells were larger than diploid cells, they also exhibited an age-associated decline in average size. Adult-specific neuronal overexpression of Myc blunted the age-associated reduction in average cell size, indicating that this phenotype is modifiable by a known cell growth regulator. To determine whether cellular changes were accompanied by tissue-level alterations, we used micro-computed tomography to assess brain volume during early adulthood. In w1118 flies, brain volume decreased with age regardless of sex, consistent with the decrease we observe in average brain cell size. Together, these findings identify early brain-wide changes in cell size and volume during early adulthood in Drosophila melanogaster as prominent features of early brain aging and provide a foundation for investigating age-dependent cellular remodeling and its underlying mechanisms and functional consequences.

cell biology↗

bioRxiv2024

Cell cycle re-entry in the aging Drosophila brain.

The brain is an organ comprised mostly of long-lived, quiescent cells that perform vital functions throughout an animals life. Due to the brains limited regenerative ability, these long-lived cells must engage unique mechanisms to cope with accumulated damage over time. We have shown that a subset of differentiated neuronal and glial cells in the fruit fly brain become polyploid during adulthood. Cell cycle re-entry in the brain has previously been associated with neurodegeneration, but there may be a more complex relationship between polyploidy and cell fitness in the brain. Here, we examine how known lifespan modifiers influence the accumulation of polyploidy in the aging fly brain. Flies aged at a low temperature, or with a low protein diet, accumulate polyploid cells in the brain more slowly than expected if this phenotype were solely regulated by lifespan mechanisms. Despite the slower accumulation of polyploid cells, animals under conditions that extend lifespan eventually reach similar levels of polyploidy in the brain as controls. Our work suggests known lifespan modifiers can influence the timing of cell cycle re-entry in the adult brain, indicating there is a flexible window of cell cycle plasticity in the aging brain.

developmental biology↗

bioRxiv2023

The RU486-dependent activation of the GeneSwitch system in adult muscles leads to severe adverse effects in Drosophila

Robust genetic systems to control the expression of transgenes in a spatial and temporal manner are a valuable asset for researchers. The GeneSwitch system induced by the drug RU486 has gained widespread use in the Drosophila community. However, some concerns were raised as negative effects were seen depending on the stock, transgene, stage and tissue under study. Here, we characterized the adverse effects triggered by activating the GeneSwitch system in adult muscles using the MHC-GS-GAL4 driver. When a control, mock UAS-RNAi transgene was induced by feeding adult flies with RU486, we found that the overall muscle structure, including myofibrils and mitochondrial shape, was significantly disrupted and led to a significant reduction in the lifespan. Remarkably, lifespan was even shorter when two copies of the driver were used even without the mock UAS-RNAi transgene. Thus, researchers should be cautious when interpreting the results given the adverse effects we found when inducing RU486-dependent MHC-GS-GAL4 in adult muscles. To counter the impact of these effects we recommend setting up additional control groups, such as a mock UAS-RNAi transgene, to validate the findings when using this inducible genetic system, as comparing the phenotypes between RU486-treated and untreated animals could be insufficient.

genetics↗

bioRxiv2022

Stimulating the sir2-pgc-1α axis rescues exercise capacity and mitochondrial respiration in Drosophila tafazzin mutants.

Cardiolipin (CL) is a phospholipid required for proper mitochondrial function. Tafazzin remodels CL to create highly unsaturated fatty acid chains. However, when tafazzin is mutated, CL remodeling is impeded, leading to mitochondrial dysfunction and the disease Barth syndrome. Patients with Barth syndrome often have severe exercise intolerance, which negatively impacts their overall quality of life. Boosting NAD+ levels can improve symptoms of other mitochondrial diseases, but its effect in the context of Barth syndrome has not been examined. We demonstrate for the first time that nicotinamide riboside (NR) can rescue exercise tolerance and mitochondrial respiration in a Drosophila tafazzin mutant and that the beneficial effects are dependent on sir2 and pgc-1. Overexpressing pgc-1 increased the total abundance of cardiolipin in mutants. In addition, muscles and neurons were identified as key targets for future therapies because sir2 or pgc-1 overexpression in either of these tissues is sufficient to restore the exercise capacity of Drosophila tafazzin mutants. Summary StatementNicotinamide riboside rescues the exercise capacity and mitochondrial function of a Drosophila model of Barth syndrome in a Sir2/Pgc-1[a] dependent manner.

physiology↗