Biology subjects

Eggert, S.

Publications and source records attributed to Eggert, S..

3 recordsLinked to original sources

bioRxiv2025

Transcriptional dynamics of the oligodendrocyte lineageand its regulation by the brain erythropoietin system

Oligodendrocytes differentiate from oligodendrocyte progenitor cells (OPC) in early postnatal development, but some oligodendrogenesis is maintained throughout adulthood, where oligodendrocyte lineage dynamics may contribute to neuroplasticity, adaptive myelination, and myelin repair. Here, we studied the effect of erythropoietin (EPO) and its receptor (EPOR) on oligodendrocyte lineage dynamics employing murine hippocampus and its myelinated fibers as model region. Using multiple stage-specific markers and single-nuclei-RNA-seq data, we find that EPO stimulates all oligodendroglial lineage cells directly, driving differentiation/maturation. Differential gene expression analysis reveals multiple EPO-regulated mRNAs, including downregulated transcripts for GABA-A receptors, fitting the known inhibition of oligodendrocyte maturation by GABA. Importantly, analogous oligodendrocyte responses are seen when endogenous EPO expression in brain is stimulated by hypoxia. Mice lacking EPOR from mature oligodendrocytes show subtle deficiencies of adult myelination in hippocampal fimbria and mild working memory deficits. These gain- and loss-of-function experiments may further suggest EPO as clinically safe treatment for remyelination therapies.

neuroscience↗

bioRxiv2023

Oligodendrocytes and neurons contribute to amyloid-β deposition in Alzheimer's disease

In Alzheimers disease (AD), amyloid-{beta} (A{beta}) is thought to be of neuronal origin. However, in single-cell RNAseq datasets from mouse and human, we found transcripts of amyloid precursor protein (APP) and the amyloidogenic-processing machinery equally abundant in oligodendrocytes (OLs). By cell-type-specific deletion of Bace1 in a humanized knock-in AD model, APPNLGF, we demonstrate that almost a third of cortical A{beta} deposited in plaques is derived from OLs. However, excitatory projection neurons must provide a threshold level of A{beta} production for plaque deposition to occur and for oligodendroglial A{beta} to co-aggregate. Indeed, very few plaques are deposited in the absence of neuronally-derived A{beta}, although soluble A{beta} species are readily detected, especially in subcortical white matter. Our data identify OLs as a source of A{beta} in vivo and further underscore a non-linear relationship between cellular A{beta} production and resulting plaque formation. Ultimately, our observations are relevant for therapeutic strategies aimed at disease prevention in AD.

neuroscience↗

bioRxiv2022

APP family member dimeric complexes are formed predominantly in synaptic compartments

The amyloid precursor protein (APP), a key player in Alzheimes disease (AD), is part of a larger gene family, including the APP like proteins APLP1 and APLP2. They share similar structures, form homo- and heterotypic dimers and exhibit overlapping functions. We investigated complex formation of the APP family members via two inducible dimerization systems, the FKBP-rapamycin based dimerization as well as cysteine induced dimerization, combined with coimmunoprecipitations and Blue Native (BN) gel analyses. Within the APP family, APLP1 shows the highest degree of dimerization and high molecular weight (HMW) complex formation. Interestingly, about 20% of APP is dimerized in cultured cells while about 50% of APP is dimerized in mouse brains, independent of age and splice forms. Furthermore, we could show that dimerized APP originates mostly from neurons and is enriched in synaptosomes. Finally, BN gel analysis of human cortex samples shows a significant decrease of APP dimers in AD patients compared to controls, suggesting that loss of dimers of full-length APP might correlate with loss of synapses in the process of AD.

neuroscience↗