Biology subjects

Boehringer, A.

Publications and source records attributed to Boehringer, A..

3 recordsLinked to original sources

bioRxiv2025

Regional BOLD variability reflects microstructural maturation and neuronal ensheathment in the preterm infant cortex

BOLD variability reflects meaningful brain activity, yet its structural and biological correlates during early development remain unknown. We aimed to investigate how BOLD variability evolves in very preterm (VPT) infants, its relationship with cortical microstructure and gene expression, and how it differs from full-term (FT) newborns at term-equivalent age (TEA). Using resting-state fMRI and multi-shell diffusion imaging, acquired in 54 VPT (longitudinally at 33-weeks GA and at TEA) and 24 FT newborns, we evaluated regional differences in cortical BOLD variability and microstructural maturation, and compared to patterns of gene expression in the fetal cortex, using the BrainSpan dataset. BOLD variability increased in primary sensory-sensorimotor and proto-DMN regions, accompanied by decreased cortical diffusivity. Gene expression analysis revealed concurrent upregulation of genes mediating gliogenesis and neuronal ensheathment. Compared to FT newborns, VPT at TEA showed decreased BOLD variability and increased cortical diffusivity. BOLD variability reflects cortical microstructure, mediated by upregulation of gliogenesis and neuronal ensheathment. Interruption of these processes by preterm birth identifies putative mechanisms of preterm brain injury.

neuroscience↗

bioRxiv2025

Neuronal Activity-Dependent Gene Dysregulation in C9orf72 i3 Neuronal Models of ALS/FTD Pathogenesis

The GGGGCC nucleotide repeat expansion (NRE) mutation in the C9orf72 (C9) gene is the most common cause of ALS and FTD. Neuronal activity plays an essential role in shaping biological processes within both healthy and neurodegenerative disease scenarios. Here, we show that at baseline conditions, C9-NRE iPSC-cortical neurons display aberrations in several pathways, including synaptic signaling and transcriptional machinery, potentially priming diseased neurons for an altered response to neuronal stimulation. Indeed, exposure to two pathophysiologically relevant stimulation modes, prolonged membrane depolarization, or a blockade of K+ channels, followed by RNA sequencing, induces a temporally divergent activity-dependent transcriptome of C9-NRE cortical neurons compared to healthy controls. This study provides new insights into how neuronal activity influences the ALS/FTD-associated transcriptome, offering a dataset that enables further exploration of pathways necessary for conferring neuronal resilience or degeneration.

neuroscience↗

bioRxiv2022

KapBeta2 is a modifier of the C9orf72-linked glycine-arginine dipeptide neurotoxicity

SummaryExpanded intronic G4C2 repeats in the C9orf72 gene cause several cases of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). These repeats are translated through a non-AUG-dependent mechanism into five different dipeptides (DPRs), including poly-glycine-arginine (GR), which is aggregation-prone and eventually neurotoxic. Here, we report that Kap{beta}2 and GR interact, co-aggregating in primary neurons in-vitro and CNS tissue in-vivo. Importantly, this interaction improves the overall survival of neurons expressing GR. Downregulation of Kap {beta}2 is detrimental to the survival of neurons only if GR is expressed, whereas increased Kap {beta}2 levels mitigate GR-mediated neurotoxicity. notably, we did not find any changes in TDP-43 localization nor in the dynamic properties of the GR aggregates when Kap{beta}2 was over-expressed. These findings support the design of therapeutic strategies aimed at modulating Kap {beta}2 levels as a potential new avenue for contrasting neurodegeneration in C9orf72-ALS/FTD.

neuroscience↗