Biology subjects

Pettyjohn-Robin, O.

Publications and source records attributed to Pettyjohn-Robin, O..

4 recordsLinked to original sources

bioRxiv2026

Rubicon modulates neuroimmune responses following traumatic brain injury

Traumatic brain injury (TBI) elicits robust neuroinflammation and oxidative stress, coupled with an acute inhibition of macro-autophagy (autophagy) in neurons and microglia. Rubicon (Rubcn), a Beclin1 interacting protein that suppresses autophagy and mediates LC3-associated phagocytosis and endocytosis (LAP/LANDO), influences inflammatory signaling in metabolic, neurodegenerative, and inflammaging diseases; yet its role in acquired brain injury has not been defined. Using a controlled cortical impact model, we investigated the role of Rubicon in acute neuroinflammatory responses following injury by comparing wild-type and Rubcn-mutant mice. Bulk-RNA sequencing of injured cortex revealed attenuated induction of inflammatory pathways and reduced activation of pro-inflammatory microglial/macrophage phenotype in injured Rubcn-mutant mice. Rubcn-mutant mice demonstrated less pronounced inhibition of autophagy during the acute phase of injury. Although the inflammatory dicerences were transient, Rubicon mutant mice exhibited improved motor coordination and gait stability during recovery. Proteomic analyses revealed the presence of a truncated Rubicon protein in the mutant mice and identified the negative regulator of reactive oxygen species (NRROS) as a novel interactor of Rubicon. Consistent with this interaction, Rubcn-mutant mice displayed markedly reduced oxidative damage, indicated by decreased lipid peroxidation after injury. Together, these findings indicate that Rubicon promotes acute neuroinflammatory and oxidative stress responses following TBI by modulating autophagy and ROS production. Rubicon mediated pathways may serve as therapeutic targets that ocer a neuroprotective strategy to improve outcomes after TBI.

neuroscience↗

bioRxiv2025

Lysosomal multi-omics reveals altered sphingolipid catabolism as driver of lysosomal dysfunction in the aging brain.

Recent data indicate that lipid composition has profound influence on the brain function and that changes in lipid homeostasis affect brain aging and predisposition to neurodegenerative diseases. Lipids dynamically reside in multiple intracellular locations and their organellar distribution is important for specific interactions and biological function. During brain aging lipid changes have been specifically noted in lysosomes, but the identity of the accumulated lipids, their interactions with other biomolecules such as proteins, and their functional relevance have not been characterized. We used mass spectrometry (MS) to assess longitudinal changes in the lipidome and proteome of lysosomes isolated from the mouse cortex, from the age of 3- to 24-months. Our statistical and machine learning analyses identified two factors demonstrating predictive power for age and differences in both lipids and proteins. Of these, factor 1 was the best predictor of sample age. Factor 1 lipids with the highest feature importance included multiple species of hexosylceramides (HexCer) and their sulfonated derivatives, sulfatides (SHexCer), all of which increased with age. Increased factor 1 proteins included myelin proteins, select sphingolipid catabolism enzymes and proteins associated with lysosomal storage diseases. Our analyses suggested that mechanisms underlying factor 1 encompass the combination of an age-dependent increase in lysosomal delivery of myelin components and alterations in lysosomal sphingolipid catabolism favoring degradation of sphingomyelin over HexCer. The overall age-related lysosomal changes resembled those observed in lysosomal storage diseases, particularly Gaucher disease, where accumulation of HexCer species is associated with lysosomal dysfunction. To corroborate factor 1 predictions, we employed a combination of biochemical, imaging and flow cytometry approaches, which confirmed alterations in sphingolipid catabolism and lysosomal accumulation of myelin components. These changes were associated with age-related alteration in lysosomal morphology, lysosomal dysfunction and inhibition of autophagy in both neurons and microglia. Our findings indicate that factors contributing to lysosomal aging resemble those observed in lysosomal storage diseases and underscore the significance of organelle-specific analyses for dissecting mechanisms contributing to brain aging.

neuroscience↗

bioRxiv2025

Inhibition of autophagy-lysosomal function exacerbates microglial and monocyte lipid metabolism reprograming and dysfunction after brain injury

CNS has an overall higher level of lipids than all tissues except adipose and contains up to 25% of total body cholesterol. Recent data demonstrate a complex crosstalk between lipid metabolism and inflammation, suggesting potential contribution of the lipid-rich brain environment to neuroinflammation. While recent data support the importance of brain lipid environment to inflammatory changes observed in age related chronic neurodegenerative diseases, in vivo interactions between lipid environment, lipid metabolism and neuroinflammation in acute brain disease and injury remain poorly understood. Here we utilize a mouse model of traumatic brain injury (TBI) to demonstrate that acute neurotrauma leads to widespread lipid metabolism reprograming in all microglial and brain associated and infiltrating monocyte populations. Additionally, we identify unique microglial and monocyte populations with higher degree of lipid metabolism reprograming and pronounced accumulation of neutral storage lipids, including cholesteryl esters and triglycerides. These lipids accumulate not only in lipid droplets but also in the microglial and monocyte lysosomes and are associated with lysosomal dysfunction and inhibition of autophagy after TBI. Our data indicate that lipid accumulation in these cells is the result of altered lipid handling rather than lipid synthesis and is triggered by phagocytosis of lipid-rich myelin debris generated after TBI. Finally, we use mice with autophagy defects in microglia and monocytes to demonstrate that further inhibition of autophagy leads to more pronounced lipid metabolism reprograming and exacerbated cellular lipid accumulation. Our data suggest a pathological feedback loop, where lipid phagocytosis causes inhibition of autophagy-lysosomal function, which in turn exacerbates cellular lipid retention, reprograming and inflammation.

neuroscience↗

bioRxiv2020

Mantis shrimp rank the shape of an object over its color during recognition

Mantis shrimp are predatory crustaceans that commonly occupy burrows in shallow, tropical waters worldwide. Most of these animals inhabit structurally complex, benthic environments with an abundance of visual features that are regularly observed, including conspecifics, predators, prey, and landmarks for use in navigation. While these animals are capable of learning and discriminating color and polarization, it is unknown what specific attributes of a visual object are important for its recognition. Here we show that mantis shrimp of the species Neogonodactylus oerstedii can learn the shape of a trained target. Furthermore, when the shape and color of a target which they had been trained to identify were placed in conflict, N. oerstedii significantly chose the target of the trained shape over the target of the trained color. Thus, we conclude that the shape of a target is more important than its color for its recognition by N. oerstedii. Our findings suggest that the shapes of learned structures, such as landmarks or other animals, are important for N. oerstedii during object recognition.

animal behavior and cognition↗