Biology subjects

Abizaid, A.

Publications and source records attributed to Abizaid, A..

4 recordsLinked to original sources

bioRxiv2025

Nucleic acid strand length governs mitochondrial reprogramming and mtROS-associated antiviral responses following TLR3 engagement

Mitochondria are important rheostats that regulate innate sensing processes by producing energy, biosynthetic precursors, and bioactive molecules that affect cellular signaling. When viral nucleic acids engage endosomal and cytosolic pattern recognition receptors (PRR), antiviral immune responses are supported by mitochondrial remodeling but the role of mitochondria in fine tuning ligand-specific responses remains incompletely understood. For example, endosomal TLR3 can detect various lengths of dsRNA (0.4-8 kb) ranging from viral segmented genomes or endogenous nucleic acids have been shown to induce distinct cytokine profiles. However, it is unclear if these differences are associated with differential mitochondrial remodeling. Here, we report that TLR3 engagement with both high (HMW; 1.5-8 kb) or low molecular weight (LMW; 0.2-1 kb) Polyinosinic:polycytidylic acid (Poly(I:C)) is associated with reduced but sustained oxidative phosphorylation (OXPHOS) activity and increased mitochondrial reactive oxygen species (mtROS) production/accumulation to support antiviral responses in bone marrow-derived macrophages (BMDM). They differed in the amount of mtROS production, their spare respiratory capacity (SRC) and their mitochondrial membrane potential (MMP). Interestingly, while uncoupling protein 2 (UCP2) was found required for antiviral cytokine production, it did not contribute to ligand specific responses. Dynamic modulation of complex I of the electron transport chain (ETC), however resulted in the differential accumulation of mtROS (HMW>LMW). Further, selectively targeting the mtROS derived from Complex I leads to augmented type I IFN production. Overall, these findings highlight that targeting specific sources of mtROS without affecting electron flow may be a potential avenue for specific augmentation of antiviral responses during viral infections.

immunology↗

bioRxiv2024

Inverse Reinforcement Learning to Study Motivation in Mouse Behavioral Paradigms

Motivation describes the underlying goals that drive animal and agent behavior. In Neuroscience, behavioral paradigms are used to quantify the motivations of mice and used to gain insights into traits and diseases which can be translated to humans. In recent years, Computer Vision models are becoming widely adopted by Neuroscientists to score mouse behavior associated with motivations such as hunger and anxiety. However, a single motivation can be expressed by multiple different behaviors, and a single behavior can be linked to multiple motivations. Therefore the ideal analysis of motivational paradigms would attempt to directly recover the underlying motivations guiding behavior, rather than indirectly score their associated behaviors. In this paper, we move towards this goal by applying Inverse Reinforcement Learning to study the underlying motivations that drive mouse behavior.

animal behavior and cognition↗

bioRxiv2024

Scale-sensitive Mouse Facial Expression Pipeline using a Surrogate Calibration Task

Emotions are complex neuro-physiological states that influence behavior. While emotions have been instrumental to our survival, they are also closely associated with prevalent disorders such as depression and anxiety. The development of treatments for these disorders has relied on animal models, in particular, mice are often used in pre-clinical testing. To compare effects between treatment groups, researchers have increasingly used machine learning to help quantify behaviors associated with emotionality. Previous work has shown that computer vision can be used to detect facial expressions in mice. In this work, we create a novel dataset for depressive-like mouse facial expressions using varying LypoPolySaccharide (LPS) dosages and demonstrate that a machine learning model trained on this dataset was able to detect differences in magnitude via dosage amount.

animal behavior and cognition↗

bioRxiv2019

Differential remodeling of the electron transport chain is required to support TLR3 and TLR4 signaling and cytokine production in macrophages

Increasing evidence suggests that mitochondria play a critical role in driving innate immune responses against bacteria and viruses. However, it is unclear if differential reprogramming of mitochondrial function contributes to the fine tuning of pathogen specific immune responses. Here, we found that TLR3 and TLR4 engagement on murine bone marrow derived macrophages was associated with differential remodeling of electron transport chain complex expression. This remodeling was associated with differential accumulation of mitochondrial and cytosolic ROS, which were required to support ligand specific inflammatory and antiviral cytokine production. We also found that the magnitude of TLR3, but not TLR4, responses were modulated by glucose availability. Under conditions of low glucose conditions, TLR3 engagement was associated with increased ETC complex III expression, increased mitochondrial and cytosolic ROS and increased inflammatory and antiviral cytokine production. This amplification was selectively reversed by targeting superoxide production from the outer Q-binding site of the ETC complex III. These results suggest that ligand specific modulation of the ETC may act as a rheostat that fine-tunes innate immune responses via mitochondrial ROS production. Modulation of these processes may represent a novel mechanism to modulate the nature as well as the magnitude of antiviral versus inflammatory immune responses.

immunology↗