Biology subjects

Weuthen, A.

Publications and source records attributed to Weuthen, A..

3 recordsLinked to original sources

bioRxiv2026

Convergent molecular signatures of ageing and injury in the peripheral nervous system

Peripheral nervous system (PNS) ageing is marked by structural and functional decline, yet it remains unclear whether ageing constitutes a distinct biological programme or reflects a chronic injury-like state. To address this, we performed an unbiased, comparative molecular analysis of PNS ageing, neuroprotective dietary restriction (DR), and nerve injury. We conducted transcriptomic and proteomic profiling of peripheral nerves from young, old and geriatric mice fed ad libitum or subjected to long-term DR, and proteomics of nerves collected at multiple time points following injury. Age-associated molecular changes followed both linear and non-linear trajectories, and DR partially attenuated these ageing-related alterations. Notably, ageing-and injury-induced proteomic signatures showed considerable similarities, supporting the concept that an aged nerve resembles an injured nerve. Together, our study provides the most comprehensive molecular resource of PNS changes during ageing, DR, and injury, enabling the definition of key molecular signatures underlying PNS physiology. All datasets are integrated into the "PNS-omics Viewer", a Shiny web application designed to facilitate data mining of the herein presented datasets (tba).

neuroscience↗

bioRxiv2025

Grey matter embedding of the cholinergic system

Integrity of acetylcholine-producing basal forebrain nuclei Ch1-4 is crucial for neurocognitive functioning and grey matter decline represents a hallmark of neuropsychiatric disorders, including Alzheimers disease, Parkinsons disease and schizophrenia. Approaches that link brain-wide grey matter atrophy with diminished cholinergic innervation from Ch1-4 projections are required for neuroimaging of disease stages and pharmacological decisions addressing cholinergic deficits. The current study assessed human magnetic resonance imaging-based markers for cholinergic nucleus subregions and synaptic targets in healthy exploration (HCP, n = 1113) and replication (IXI, n = 587) cohorts. Ch1-3 and Ch4 were delineated at 50% cytoarchitectonic probability to determine their grey matter coupling patterns using structural covariance analyses. Spatial colocalization with vesicular acetylcholine transporter, M1-muscarinic and 4{beta}2-nicotinic receptor density quantified the correspondence with synaptic cholinergic markers. All individual-level cholinergic nucleus and target region indices showed good test-retest reliability (R [≥] 0.80) when restricted to voxels with at least 10% grey matter probability. Spatial colocalization with presynaptic acetylcholine transporters emphasized a cholinergic nature of Ch1-4 grey matter and its coupling with corticopetal projections such as amygdala, insula and cingulate cortices. Subcortical gradients of M1-muscarinic receptor density and the Ch1-3 structural covariance map, however, dominated in locations of striatal cholinergic interneurons, such as nucleus accumbens, caudate nucleus and putamen. Ch4 covaried with medial thalamus and hippocampus, while both subregions structural covariance networks converged in a posterolateral Ch4 extensions, potentially resembling subputaminal nucleus of Ayala. The results emphasize Ch1-4 morphometry as marker for acetylcholine-driven brain regions and describe neuroimaging strategies to indicate synaptic cholinergic involvement. Significance StatementPrevious studies have suggested that grey matter alterations in basal forebrain Ch1-4 nuclei indicate cholinergic deficits in neurodegenerative and psychiatric pathologies. However, the use of Ch1-4 volume as a marker of cholinergic system integrity has yet to be validated. Additionally, there is a lack of non-invasive procedures to quantify integrity of regions innervated by its cholinergic projections. Our results suggest that grey matter coupling with Ch1-4 is a sensitive cholinergic system marker, mimicking the density distribution of synaptic cholinergic innervation. Furthermore, we introduce grey matter-based target region indices, evaluate their robustness in individual participants and describe regional contributions to M1-muscarinic, 4{beta}2-nicotinic and vesicular acetylcholine transporter gradients. The study advances our understanding of cholinergic circuits in vivo using magnetic resonance imaging.

neuroscience↗

bioRxiv2023

Cholinergic modulation of motor sequence learning

The cholinergic system plays a key role in motor function, but whether pharmacological modulation of cholinergic activity affects motor sequence learning is unknown. The acetylcholine receptor antagonist biperiden, an established treatment in movement disorders, reduces attentional modulation, but whether it influences motor sequence learning is not clear. Using a randomized, double-blind placebo-controlled crossover design, we tested thirty healthy young participants and show that biperiden impairs production of sequential finger movements following a fixed but not a random sequence. A similar interaction was observed in widespread oscillatory broadband power changes (4-25 Hz) in the motor sequence learning network after receiving biperiden, with greater power in the theta, alpha, and beta bands over ipsilateral motor and bilateral parietal-occipital areas. The reduced theta power during a fixed compared to random sequence, likely reflecting disengagement of top-down attention to sensory processes, was disrupted by biperiden. The alpha synchronization during learned sequences, reflecting sensory gating and lower visuospatial attention requirements for the learned, compared with visuomotor responses to a random sequence, was greater after biperiden, potentially reflecting excessive visuospatial attention reduction following biperiden, also affecting visuomotor responding required to enable sequence learning. Beta oscillations facilitate sequence learning by integrating visual and somatosensory inputs, stabilizing learned sequences, and promoting prediction of the next stimulus. The beta synchronization after biperiden fits with a disruption of the selective visuospatial attention enhancement associated with initial sequence learning. These findings highlight the role of cholinergic processes in motor sequence learning.

neuroscience↗