Biology subjects

Duman, J. G.

Publications and source records attributed to Duman, J. G..

2 recordsLinked to original sources

bioRxiv2026

Transcriptional and DNA Methylation Changes in the Hippocampus and Prefrontal Cortex after Fractionated Cranial Radiation in Mice

Fractionated whole-brain irradiation is essential for treating brain tumors, but many long-term survivors develop cognitive decline whose molecular basis is poorly understood. We asked which cell types and gene programs change late after irradiation, how the hippocampus and prefrontal cortex compare, and whether DNA methylation changes affect the same genes or programs. Male and female mice received whole-brain irradiation (5 x 4 Gy) or anesthesia alone. Irradiated mice showed persistent deficits in executive function and spatial memory. Eleven weeks after irradiation, single-nucleus RNA sequencing and whole-genome bisulfite sequencing of pooled hippocampal (CA1-3) and prefrontal tissue showed cell-type-specific transcriptional changes in neurons of both regions. Both regions showed reduced ribosomal-protein gene expression and changes in adhesion genes, with reduced respiratory-chain genes in prefrontal neurons and bidirectional synaptic gene changes in hippocampus. Differentially methylated regions were enriched at promoters, with hypermethylation predominating in three of the four sex-by-region contrasts. Methylation and gene expression changes pointed to overlapping synaptic and signaling programs, largely through different genes.

neuroscience↗

bioRxiv2025

Primary cortical neurons form calcium-phosphate sheets with a bone-precursor-like ultrastructure

Calcium-phosphate (CaP) is a ubiquitous inorganic compound that plays an important structural role in healthy bone and teeth formation, but its pathologic buildup can occur in dyshomeostatic calcium disorders like Alzheimers disease and Leigh syndrome. The nexus of pathologic extracellular CaP in the nervous system is not well understood, but prior evidence suggests mitochondria could be a source. We have observed mitochondria-sized sheet-like CaP aggregates within functional wild type cortical neuron cultures at 1 and 20 DIV. Neurons were extracted from embryonic day 18 (E18) rat embryos following standard protocols to study neuronal structure and function. We have used a combination of cryo-ET, cryo-CLEM, and LDSAED to demonstrate that these aggregates are octacalcium phosphate-like, are associated with mitochondria, and that at least a portion are extruded via migrasomes. Visually similar aggregates were previously observed in Huntingtons disease model neurons, but in that study they were not observed in WT controls. These findings show that this CaP aggregation process occurs routinely in WT neurons and may reveal an important link for how mitochondria may participate in calcification, highlighting them as potential therapeutic targets in neurological disorders characterized by pathological calcification, such as Alzheimers disease.

neuroscience↗