Biology subjects

Massey, N.

Publications and source records attributed to Massey, N..

4 recordsLinked to original sources

bioRxiv2025

Automated Seizure Detection in Animal EEG Signals

Automated seizure detection in animal electroencephalography (EEG) is crucial for accelerating epilepsy research. While machine learning (ML) and deep learning (DL) techniques have shown promise in seizure detection for human EEG and some rodent models, their application to chemically diverse animal data remains limited. In particular, no prior work has explored deep learning approaches for EEG data where seizure/epilepsy was induced by exposure to Soman (GD), a potent agent known to generate complex and variable seizure dynamics. In this work, we evaluate deep recurrent neural networks--Gated Recurrent Units (GRU) and Long Short-Term Memory networks (LSTM)--for seizure detection in EEG signals acquired by single channel (bipotential electrodes) from the rats exposed to either kainate or GD, which later animals developed epilepsy (measured by spontaneously recurring seizures). We benchmark these models against classical baselines including Random Forest and XGBoost, using intracranial EEG data from eight animals. Our results show that GRU and LSTM substantially outperform other shallow models in both accuracy and robustness across EEG traces.

animal behavior and cognition↗

bioRxiv2025

Exploring the Role of Kv1.3 and MAPK14 in Mediating Microglial Oxidative Stress and Neuroinflammation Following Organic Dust Exposure

BackgroundAgricultural contaminants, including inhaled organic dust (OD) and gases, are known to cause inflammation in the lungs and the brain. We investigated the role of the potassium channel Kv1.3 in organic dust (OD)-induced neuroinflammation models. Kv1.3 channels play a multifaceted role in microglial immune modulation, cancer, neurodegenerative diseases, and constitute a potential therapeutic target. MethodsWe used in vivo (C57BL/6 mice), in vitro (microglial cell line, primary microglia), and ex vivo (brain slice culture) models of OD-induced neuroinflammation. A sterile OD extract (ODE) was prepared, and mice were exposed to either normal saline or ODE intra-nasally for 5 weeks (5 days/week) to simulate an occupational exposure scenario. Primary microglia were isolated from neonatal mice for total RNA sequencing (RNA-seq). The ODE-induced expression of Kv1.3 was quantified using in vitro and ex vivo models with and without PAP-1 treatments. Exposure-induced changes in cytokines and reactive species markers were measured. Using western blot, we quantified phosphorylated p38 MAPK14 (p-p38 MAPK) and NOX2. We measured the currents through Kv1.3 channels using a microglial patch-clamp assay. ResultsExposure to ODE increased the expression of Kv1.3 and p-p38 MAPK in mouse microglia without affecting the Kv1.3 currents at the cell surface. Exposure increased the levels of inflammatory cytokines and NOX2. Kv1.3 inhibition with PAP-1 decreased inflammatory markers (TNF- and IL-6), levels of Kv1.3, p-p38 MAPK, NOX2, and nitrites. ConclusionOur study revealed that pharmacological inhibition of Kv1.3 potassium channels reduces ODE-induced neuroinflammation by decreasing inflammatory and oxidative stress markers.

pharmacology and toxicology↗

bioRxiv2020

Organic dust induced mitochondrial dysfunction could be targeted via cGAS-STING or mitochondrial NOX-2 inhibition

ABSTRACTOrganic dust (OD) exposure in animal production industries poses serious respiratory and other health risks. OD consists of microbial products and particulate matter and OD exposure induced respiratory inflammation is under intense investigation. However, the effect of OD exposure on brain largely remains unknown. Recently, we have shown that OD exposure of brain microglial cells induces an inflammatory phenotype with the release of mitochondrial DNA (mt-DNA). Therefore, we tested a hypothesis that OD-exposure induced secreted mt-DNA signaling drives the inflammation. OD samples were collected from commercial swine operations and a filter sterilized OD extract (ODE) was prepared. Mouse (C57BL/6) microglial cell line was treated with medium or ODE (5%) for 48 hours along with either PBS or mitoapocynin (MA, 10 μM, NOX-2 inhibitor). Microglia treated with control or anti-STING siRNA were exposed to medium or ODE. Next, mouse (C57BL/6) pups were euthanized under an approved protocol, organotypic brain slice cultures (BSCs) were prepared and exposed to medium or ODE with or without MA treatment daily for five days. Culture supernatant, cell pellets and mt-free cytosolic fractions were processed to quantify mt-superoxide, mt-DNA, cytochrome C, TFAM, mitochondrial stress markers and mt-DNA induced signaling via cGAS-STING and TLR9. Data were analyzed using one-way ANOVA and post-hoc tests. A p value of ≤ 0.05 was considered significant. ODE exposure increased the mt-superoxide formation andMA treatment decreased the ODE-induced mt-DNA release into cytosol. ODE exposure increased the cytochrome C and TFAM levels. ODE increased MFN1/2 and PINK1 but not DRP1 and MA treatment decreased the MFN2 expression. MA treatment decreased the ODE-exposure induced mt-DNA signaling via cGAS-STING and TLR9. Anti-STING siRNA decreased the ODE-induced increase in IRF3, IFN-β and Iba1 expression. In BSCs, MA-treatment decreased the ODE induced TNF-α, IL-6 and MFN1. Taken together, OD exposure induced mt-DNA signaling could be curtailed through mitochondrial NOX-2 inhibition or STING suppression to reduce neuroinflammation.Competing Interest StatementAGK has an equity interest in PK Biosciences Corporation located in Ames, IA. The terms of this arrangement have been reviewed and approved by Iowa State University per its conflict of interest policies. All other authors have declared no potential conflicts of interest.View Full Text

cell biology↗

bioRxiv2020

Organic Dust Exposure Induces Stress Response and Mitochondrial Dysfunction in Monocytic Cells

Exposure to airborne organic dust (OD), rich in microbial pathogen-associated molecular patterns, has been shown to induce inflammatory responses in the lung resulting in changes in airway structure and function. A common manifestation in lung inflammation is the occurrence of altered mitochondrial structure and bioenergetics, consequently regulating mitochondrial ROS (mROS) and creating a vicious cycle of mitochondrial dysfunction.The role of mitochondrial dysfunction in airway diseases such as COPD and asthma is well known. However, whether OD exposure induces mitochondrial dysfunction largely remains unknown. Therefore, in this study, we tested a hypothesis that OD exposure induces mitochondrial stress using a human monocytic cell line (THP-1). We examined the mechanisms of organic dust extract (ODE) exposure-induced mitochondrial structural and functional changes in THP-1 cells.In addition, the effect of co-exposure to ethyl pyruvate (EP), a known anti-inflammatory agent, or mitoapocynin (MA), a mitochondria targeting NOX2 inhibitor was examined. Transmission electron microscopy images showed significant changes in cellular and organelle morphology upon ODE exposure. ODE exposure with and without EP co-treatment increased the mtDNA leakage into the cytosol. Next, ODE exposure increased the PINK1 and Parkin expression, cytoplasmic cytochrome c levels and reduced mitochondrial mass and cell viability, indicating mitophagy. MA treatment was partially protective by decreasing Parkin expression, mtDNA and cytochrome c release and increasing cell viability.Competing Interest StatementAGK has an equity interest in PK Biosciences Corporation located in Ames, IA. The terms of this arrangement have been reviewed and approved by Iowa State University per its conflict of interest policies. All other authors have declared no potential conflicts of interest. AbbreviationsODOrganic DustODEOrgaic Dust ExtractEPEthyl PyruvateMAMitoapocyninLPSLipopolysaccharidePGNPeptidoglycanPAMPsPathogen Associated Molecular PatternsCOPDChronic Obstructive Pulmonary DiseaseAHRAirway hyperresponsivenessROSReactive Oxygen SpeciesRNSReactive Nitrogen SpeciesATPAdenosine TriphosphateOXPHOSOxidative PhosphorylationHMGB1High Mobility Group Box 1STATSignal Transducer and Activator of TranscriptionTPPTriphenylphosphoniumMPTP1-Methyl-4-Phenyl-1,2,3,6-TetrahydropyridineiNOSinducible Nitric Oxide SynthaseNOXNADPH OxidaseMTT3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromideTEMTransmission Electron MicroscopyDMSODimethyl SufoxidemtND1mitochondrial NADH dehydrogenase 1MFNMitofusinOPA1Optic Atrophy 1DRP1Dynamin-related protein 1EREndoplasmic ReticulumPINK1PTEN- induced kinase 1BNIP3Bcl-2 Homology 3 (BH3)-onlyMPTMitochondrial Permeability TransitionCOX4i2Cytochrome C Oxidase subunit 4 isoform 2ETCElectron Transport ChainSOD2Superoxide Dismutase 2mtDAMPsmitochondrial Damage Associated Molecular PattersmtTFAmitochondrial Transcription Factor AMGCMultinucleated Giant CellFBRForeign Body ReactionsOMMOuter Mitochondrial MembraneIMMInner Mitochondrial MembraneIMSIntermembrane SpaceILInterleukincGAScyclic GMP-AMP synthaseTLRToll-like receptorRAGEReceptor for advanced glycation end productsVDACVoltage-dependent anion channelView Full Text

cell biology↗