Biology subjects

Ogundare, S. O.

Publications and source records attributed to Ogundare, S. O..

3 recordsLinked to original sources

bioRxiv2024

The Dorsal Column Nuclei Scales Mechanical Allodynia During Neuropathic Pain

Tactile perception relies on reliable transmission and modulation of low-threshold information as it travels from the periphery to the brain. During pathological conditions, tactile stimuli can aberrantly engage nociceptive pathways leading to the perception of touch as pain, known as mechanical allodynia. Two main drivers of peripheral tactile information, low-threshold mechanoreceptors (LTMRs) and postsynaptic dorsal column neurons (PSDCs), terminate in the brainstem dorsal column nuclei (DCN). Activity within the DRG, spinal cord, and DCN have all been implicated in mediating allodynia, yet the DCN remains understudied at the cellular, circuit, and functional levels compared to the other two. Here, we show that the gracile nucleus (Gr) of the DCN mediates tactile sensitivity for low-threshold stimuli and contributes to mechanical allodynia during neuropathic pain in mice. We found that the Gr contains local inhibitory interneurons in addition to thalamus-projecting neurons, which are differentially innervated by primary afferents and spinal inputs. Functional manipulations of these distinct Gr neuronal populations resulted in bidirectional changes to tactile sensitivity, but did not affect noxious mechanical or thermal sensitivity. During neuropathic pain, silencing Gr projection neurons or activating Gr inhibitory neurons was able to reduce tactile hypersensitivity, and enhancing inhibition was able to ameliorate paw withdrawal signatures of neuropathic pain, like shaking. Collectively, these results suggest that the Gr plays a specific role in mediating hypersensitivity to low-threshold, innocuous mechanical stimuli during neuropathic pain, and that Gr activity contributes to affective, pain-associated phenotypes of mechanical allodynia. Therefore, these brainstem circuits work in tandem with traditional spinal circuits underlying allodynia, resulting in enhanced signaling of tactile stimuli in the brain during neuropathic pain.

neuroscience↗

bioRxiv2022

Rapid Carbon Dioxide Capture and Short-Term Biocompatible Sequestration in Aquatic Environments by Monoethanolamine Scrubbing within Calcium Alginate Gel

Alginate is a biopolymer extracted from the cell walls of algae, and can crosslink with divalent cations to form an insoluble hydrogel. In this paper, we develop a method to immobilize monoethanolamine, an amine CO2 scrubber, within calcium alginate gel. By mixing monoethanolamine into an alginate solution as the gel was formed, we suspended the compound in the gel, facilitating a means to capture carbon dioxide directly from aquatic environments into the gel, while tethering monoethanolamine and the products formed from CO2 capture to the gel. To delay the eventual diffusion of monoethanolamine out of the gel, we investigated (1) the effect of increasing alginate concentration and (2) the effect of additional alginate layers on the outward diffusion of dye placed in the center of the bead. Using ultraviolet-visible spectroscopy to quantify diffusion rates over time, we determined that increased alginate concentration paired with increased layering significantly decreased the rate of outward diffusion. Finally, we prepared beads using North Atlantic seawater as a solvent and compared the rate of dye leakage in seawater and distilled water to that in beads prepared in distilled water. Expectedly, we concluded that beads prepared with solvents isotonic to their environments would exhibit less leakage as well as greater mechanical stability, resisting swelling, bursting, or splitting behaviors.

bioengineering↗

bioRxiv2021

Use of Induced Pluripotent Stem Cells to Build Isogenic Systems and Investigate Type 1 Diabetes

Type 1 diabetes is a disease that arises due to complex immunogenetic mechanisms. Key cell-cell interactions involved in the pathogenesis of T1D are activation of autoreactive T cells by dendritic cells (DC), migration of T cells across endothelial cells (EC) lining capillary walls into the islets of Langerhans, interaction of T cells with macrophages in the islets, and killing of {beta}-cells by autoreactive CD8+ T cells. Overall, pathogenic cell-cell interactions are likely regulated by the individuals collection of genetic T1D-risk variants. To accurately model the role of genetics, it is essential to build systems to interrogate single candidate genes in isolation during the interactions of cells that are essential for disease development. However, obtaining single-donor matched cells relevant to T1D is a challenge. Sourcing these genetic variants from human induced pluripotent stem cells (iPSC) avoids this limitation. Herein, we have differentiated iPSC from one donor into DC, macrophages, EC, and {beta}-cells. Additionally, we also engineered T cell avatars from the same donor to provide an in vitro platform to study genetic influences on these critical cellular interactions. This proof of concept demonstrates the ability to derive an isogenic system from a single donor to study these relevant cell-cell interactions. Our system constitutes an interdisciplinary approach with a controlled environment that provides a proof-of-concept for future studies to determine the role of disease alleles (e.g. IFIH1, PTPN22, SH2B3, TYK2) in regulating cell-cell interactions and cell-specific contributions to the pathogenesis of T1D.

immunology↗