Biology subjects

Brown, J. E.

Publications and source records attributed to Brown, J. E..

3 recordsLinked to original sources

bioRxiv2023

Altered metabolic function induced by amyloid-beta oligomers and PSEN1-mutations in iPSC-derived astrocytes.

Altered energy metabolism in Alzheimers disease (AD) is considered a major pathological hallmark implicated in the early stages of the disease process. Astrocytes play a central role in brain homeostasis and are increasingly implicated in multiple neurodegenerative diseases. We report that astrocytes differentiated from early onset familial Alzheimers disease (fAD) patients or control cells treated with Amyloid {beta} oligomers exhibit significant changes in their metabolism including glucose uptake, glutamate uptake and lactate release, with increases in oxidative and glycolytic metabolism. Furthermore, we demonstrate evidence of gliosis in fAD astrocytes in addition to a change in metabolic pathways including glutamate, purines, arginine, and the citric acid cycle. Homeostatic responses to brain activity and cellular metabolism are central to normal brain function. However, altered brain metabolism and cellular stress present significant risk factors for the onset and progression of neurodegenerative disease. This study demonstrates that fAD derived astrocytes present multiple metabolic and disease associated phenotypes early in their development suggesting that chronic alterations in fAD patient early in life that present significant risk factors for disease progression in mid-life and suggest key targets for potential diagnostic features and therapeutic agents late onset dementia in midlife.

neuroscience↗

bioRxiv2023

An In-Silico Testbed for Fast and Accurate MR Labeling of Orthopaedic Implants

AO_SCPLOWBSTRACTC_SCPLOWOne limitation on the ability to monitor health in older adults using Magnetic Resonance (MR) imaging is the presence of implants, where the prevalence of implantable devices (orthopedic, cardiac, neuromodulation) increases in the population, as does the pervasiveness of conditions requiring MRI studies for diagnosis (musculoskeletal diseases, infections, or cancer). The present study describes a novel multiphysics implant modeling testbed using the following approaches with two examples: - an in-silico human model based on the widely available Visible Human Project (VHP) cryo-section dataset; - a finite element method (FEM) modeling software workbench from Ansys (Electronics Desktop/Mechanical) to model MR radio frequency (RF) coils and the temperature rise modeling in heterogeneous media. The in-silico VHP Female model (250 parts with an additional 40 components specifically characterizing embedded implants and resultant surrounding tissues) corresponds to a 60-year-old female with a body mass index (BMI) of 36. The testbed includes the FEM-compatible in-silico human model, an implant embedding procedure, a generic parameterizable MRI RF birdcage two-port coil model, a workflow for computing heat sources on the implant surface and in adjacent tissues, and a thermal FEM solver directly linked to the MR coil simulator to determine implant heating based on an MR imaging study protocol. The primary target is MR labeling of large orthopaedic implants. The testbed has very recently been approved by the US Food and Drug Administration (FDA) as a medical device development tool (MDDT) for 1.5 T orthopaedic implant examinations.

biophysics↗

bioRxiv2023

Angular head velocity cells within brainstem nuclei projecting to the head direction circuit

An animals perceived sense of orientation depends upon the head direction (HD) system found in several limbic structures and depends upon an intact peripheral vestibular labyrinth. However, how the vestibular system influences the generation, maintenance, and updating of the HD signal remains poorly understood. Anatomical and lesion studies point towards three key brainstem nuclei as being potential critical components in generating the HD signal: nucleus prepositus hypoglossi (NPH), supragenual nucleus (SGN), and dorsal paragigantocellularis reticular nuclei (PGRNd). Collectively, these nuclei are situated between the vestibular nuclei and the dorsal tegmental and lateral mammillary nuclei, which are thought to serve as the origin of the HD signal. To test this hypothesis, extracellular recordings were made in these areas while rats either freely foraged in a cylindrical environment or were restrained and rotated passively. During foraging, a large subset of cells in all three nuclei exhibited activity that correlated with changes in the rats angular head velocity (AHV). Two fundamental types of AHV cells were observed: 1) symmetrical AHV cells increased or decreased their neural firing with increases in AHV regardless of the direction of rotation; 2) asymmetrical AHV cells responded differentially to clockwise (CW) and counter-clockwise (CCW) head rotations. When rats were passively rotated, some AHV cells remained sensitive to AHV whereas others had attenuated firing. In addition, a large number of AHV cells were modulated by linear head velocity. These results indicate the types of information conveyed in the ascending vestibular pathways that are responsible for generating the HD signal. Significance StatementExtracellular recording of brainstem nuclei (nucleus prepositus hypoglossi, supragenual nucleus, and dorsal paragigantocellularis reticular nucleus) that project to the head direction circuit identified different types of angular head velocity (AHV) cells while rats freely foraged in a cylindrical environment. The firing of many cells was also modulated by linear velocity. When rats were restrained and passively rotated some cells remained sensitive to AHV, whereas others had attenuated firing. These brainstem nuclei provide critical information about the rotational movement of the rats head in the azimuthal plane.

animal behavior and cognition↗