Tieu, E. K. | bioRxiv Science

bioRxiv2025

DRP1 induces neuroinflammation via transcriptional regulation of NF-ĸB

Neuroinflammation is a major pathogenic mechanism in neurodegenerative diseases. Understanding the regulation of neuroinflammation is critical to therapeutic development. We report here that dynamin related protein 1 (DRP1), well-recognized for its role in mitochondrial fission, is a transcription factor that regulates neuroinflammation. Using multiple inflammatory models, we provide evidence demonstrating that DRP1, when challenged with pro-inflammatory lipopolysaccharides, translocates from the cytosol to the nucleus, then binds to the promoter region of Rela (encoding NF-{kappa}B) to activate its gene products and other downstream inflammatory cytokines. Our data also demonstrate the significant role of the proinflammatory lipocalin 2 in the brain. In combination, this study highlights a previously unidentified function of DRP1 in mediating neuroinflammation via the NF-{kappa}B-lipocalin 2 axis. Through such mechanisms of DRP1, this study also provides potential therapeutic targets for neurodegenerative diseases and other conditions linked to inflammation.

neuroscience↗

bioRxiv2024

A deep learning-based approach for unbiased kinematic analysis in CNS injury

Traumatic spinal cord injury (SCI) is a devastating condition that impacts over 300,000 individuals in the US alone. Depending on the severity of the injury, SCI can lead to varying degrees of sensorimotor deficits and paralysis. Despite advances in our understanding of the underlying pathological mechanisms of SCI and the identification of promising molecular targets for repair and functional restoration, few therapies have made it into clinical use. To improve the success rate of clinical translation, more robust, sensitive, and reproducible means of functional assessment are required. The gold standards for the evaluation of locomotion in rodents with SCI are the Basso Beattie Bresnahan (BBB) and Basso Mouse Scale (BMS) tests. To overcome the shortcomings of current methods, we developed two separate marker-less kinematic analysis paradigms in mice, MotorBox and MotoRater, based on deep-learning algorithms generated with the DeepLabCut open-source toolbox. The MotorBox system uses an originally designed, custom-made chamber, and the MotoRater system was implemented on a commercially available MotoRater device. We validated the MotorBox and MotoRater systems by comparing them with the traditional BMS test and extracted metrics of movement and gait that can provide an accurate and sensitive representation of mouse locomotor function post-injury, while eliminating investigator bias and variability. The integration of MotorBox and/or MotoRater assessments with BMS scoring will provide a much wider range of information on specific aspects of locomotion, ensuring the accuracy, rigor, and reproducibility of behavioral outcomes after SCI. HighlightsO_LIMotorBox and MotoRater systems are two novel marker-less kinematic analysis paradigms in mice, based on deep-learning algorithms generated with DeepLabCut. C_LIO_LIMotorBox and MotoRater systems are highly sensitive, accurate and unbiased in analyzing locomotor behavior in mice. C_LIO_LIMotorBox and MotoRater systems allow for sensitive detection of SCI-induced changes in movement metrics, including range of motion, gait, coordination, and speed. C_LIO_LIMotorBox and MotoRater systems allow for detection of movement metrics not measurable with the BMS. C_LI

neuroscience↗