Biology subjects

Deuchars, S.

Publications and source records attributed to Deuchars, S..

3 recordsLinked to original sources

bioRxiv2023

The autonomic effects of transcutaneous auricular nerve stimulation at different sites on the external auricle of the ear

Transcutaneous auricular nerve stimulation (tANS) applied to specific parts of the external ear has positive health effects in both healthy volunteers and patient groups. However, due to differences between studies in ear stimulation sites and extent of effect on autonomic variables, it is challenging to determine what part of the external ear is the optimum site for electrode placement. This study investigated the autonomic effects of bilateral tANS at four different sites on the external auricle of the ear: tragus, cymba concha, helix and earlobe. tANS was performed using modified surface electrodes connected to a transcutaneous electrical nerve stimulation (TENS) machine. Participants (n = 24) each underwent four sessions where a 15 minute period of stimulation (pulse width: 200 s; pulse frequency: 30 Hz; current: adjusted to sensory threshold) was applied bilaterally to either the tragus, cymba concha, helix or earlobe. Heart rate and blood pressure were continuously recorded during 10-minute baseline, 15-minute stimulation and 10-minute recovery periods. Heart rate variability (HRV) was derived. Results showed that regardless of site, stimulation significantly influenced measures of HRV. Baseline LF/HF ratio predicted change in LF/HF ratio during stimulation for each site and for all sites combined. Response (i.e. change in LF/HF ratio between baseline and stimulation) was closely linked with measures reflecting starting autonomic function. This demonstrates the importance of evaluating how autonomic function is modulated by tANS in individual participants (as well as the whole group). These findings have key implications for adopting a tailored approach when considering the therapeutic/clinical applications of tANS.

neuroscience↗

bioRxiv2022

The in-tissue molecular architecture of β-amyloid pathology in the mammalian brain.

Amyloid plaques composed of extracellular focal deposition of A{beta} fibrils are a hallmark of Alzheimers disease (AD). Cryo-EM structures of A{beta} fibrils purified from human AD brain tissue post mortem have recently been determined. However, the molecular architecture of amyloid plaques in the context of fresh, unfixed mammalian brain tissue is unknown. Here, using cryogenic correlated light and electron tomography we report the native, in situ molecular architecture of A{beta} fibrils in the brain of a mouse model containing the Arctic familial AD mutation (AppNL-G-F) and an atomic model of Arctic A{beta} fibril purified from the brains of these animals. We show that in-tissue A{beta} fibrils are arranged in a lattice or in parallel bundles within a plaque, and are interdigitated by subcellular compartments, exosomes, extracellular droplets and extracellular multilamellar bodies. At the atomic level, the Arctic A{beta} fibril differs significantly from earlier structures of A{beta} amyloid extracted from AppNL-F mice models and human AD brain tissue, showing a striking effect of the Arctic mutation (E22G) on fibril structure. Cryo-electron tomography of ex vivo purified and in-tissue amyloid revealed an ensemble of additional fibrillar species, including thin protofilament-like rods and branched fibrils. Together, these results provide a structural model for the dense network architecture that characterises {beta}-amyloid plaque pathology.

neuroscience↗

bioRxiv2022

GABAergic regulation of cell proliferation within the adult mouse spinal cord

Manipulation of neural stem cell proliferation and differentiation in the postnatal CNS is receiving significant attention due to therapeutic potential. In the spinal cord, such manipulations may promote repair in conditions such as multiple sclerosis or spinal cord injury, but may also limit excessive cell proliferation contributing to tumours such as ependymomas. Here we show that when ambient GABA is increased in vigabatrin-treated or decreased in glutamic acid decarboxylase67-green fluorescent protein (GAD67-GFP) mice, the numbers of proliferating cells respectively decreased or increased. Thus, intrinsic spinal cord GABA levels are correlated with the extent of cell proliferation, providing important evidence for the possibility of manipulating these levels. Diazepam binding inhibitor, an endogenous protein that interacts with GABA receptors and its breakdown product, octadecaneuropeptide, which preferentially activates central benzodiazepine (CBR) sites, were highly expressed in the spinal cord, especially in ependymal cells surrounding the central canal. Furthermore, animals with reduced CBR activation via treatment with flumazenil or Ro15-4513, or with a G2F77I mutation in the CBR binding site had greater numbers of Ethynyl-2-deoxyuridine positive cells compared to control, which maintained their stem cell status since the proportion of newly proliferated cells becoming oligodendrocytes or astrocytes was significantly lower. Altering endogenous GABA levels or modulating GABAergic signaling through specific sites on the GABA receptors therefore influences NSC proliferation in the adult spinal cord. These findings provide a basis for further study into how GABAergic signaling could be manipulated to enable spinal cord self-regeneration and recovery or limit pathological proliferative activity.

neuroscience↗