Mechanism by which Rab5 promotes regeneration and functional recovery of zebrafish Mauthner axons.

JOURNAL/nrgr/04.03/01300535-202506000-00031/figure1/v/2024-08-05T133530Z/r/image-tiff Rab5 is a GTPase protein that is involved in intracellular membrane trafficking. It functions by binding to various effector proteins and regulating cellular responses, including the formation of transport vesicles and their fusion with the cellular membrane. Rab5 has been reported to play an important role in the development of the zebrafish embryo; however, its role in axonal regeneration in the central nervous system remains unclear. In this study, we established a zebrafish Mauthner cell model of axonal injury using single-cell electroporation and two-photon axotomy techniques. We found that overexpression of Rab5 in single Mauthner cells promoted marked axonal regeneration and increased the number of intra-axonal transport vesicles. In contrast, treatment of zebrafish larvae with the Rab kinase inhibitor CID-1067700 markedly inhibited axonal regeneration in Mauthner cells. We also found that Rab5 activated phosphatidylinositol 3-kinase (PI3K) during axonal repair of Mauthner cells and promoted the recovery of zebrafish locomotor function. Additionally, rapamycin, an inhibitor of the mechanistic target of rapamycin downstream of PI3K, markedly hindered axonal regeneration. These findings suggest that Rab5 promotes the axonal regeneration of injured zebrafish Mauthner cells by activating the PI3K signaling pathway.

CM082 suppresses hypoxia-induced retinal neovascularization in larval zebrafish.

Retinal neovascularization is a common feature of several ocular neovascular diseases, which are the leading cause of blindness in the world. Current treatments are administered through invasive intravitreal injections, leading to poor patient compliance, serious ocular complications and heavy economic burdens. Thus, an alternative less or non-invasive therapeutic strategy is in demand. Here, a non-invasive oral tyrosine kinase inhibitor, CM082, was evaluated in a retinal neovascularization model induced by hypoxia in zebrafish larvae. We found that CM082 effectively suppressed retinal neovascularization, rescued cell loss in the retinal ganglion cell layer, and rescued the visual function deficiency. Our results elucidated that CM082 mediated its therapeutic efficacy primarily through the inhibition of Vegfr2 phosphorylation. The findings demonstrated that CM082 possessed strong antiangiogenic effects and may serve as a potential treatment for angiogenesis in ocular neovascular diseases.

Porous Magnetic Soft Grippers for Fast and Gentle Grasping of Delicate Living Objects.

Magnetic soft grippers have attracted intensive interest due to their untethered controllability, rapid response, and biological safety. However, manipulating living objects requires a simultaneous increase in shape adaptability and gripping force, which are typically mutually exclusive. Increasing the magnetic particle content enhances the magnetic strength but also increases the elastic modulus, leading to low adaptability and high impact force. Here, a porous magnetic soft gripper (PMSG) is developed by integrating a porous structure into a magnetic silicone elastomer. The design of porous hard magnetic composite is characterized by high magnetization, low modulus, and rough surface. It offers the PMSG good compliance, high gripping force, and low impact force at fast gripping. The PMSG is capable of performing a variety of tasks, including the fast and gentle grasping of delicate living objects. The study provides insight into the design of novel magnetic grippers and may offer a promising outlook for biomedical or scientific applications in the manipulation of delicate organisms.

Sevoflurane postconditioning ameliorates cerebral hypoxia/reoxygenation injury in zebrafish involving the Akt/GSK-3ß pathway activation and the microtubule-associated protein 2 promotion.

Sevoflurane postconditioning has been shown to provide neuroprotection against cerebral hypoxia-ischemia injury, but the mechanisms remain elusive. Microtubule-associated protein 2 (MAP2) is implicated in early neuronal hypoxia-ischemia injury. This study aimed to investigate whether the neuroprotective effects of sevoflurane postconditioning are related to the Akt/GSK-3ß pathway and its downstream target MAP2 in zebrafish hypoxia/reoxygenation (H/R) model. Sevoflurane postconditioning or GSK-3ß inhibitor TDZD-8 were used to treat H/R zebrafish. The cerebral infarction, neuronal apoptosis, and mitochondrial changes were evaluated using TTC staining, TUNEL staining, and transmission electron microscopy, respectively. The distribution of MAP2 in the brain was determined by immunofluorescence imaging. The levels of Akt, p-Akt, GSK-3ß, p-GSK-3ß, and MAP2 proteins were evaluated by Western blotting. The neurobehavioral recovery of zebrafish was assessed based on optokinetic response behavior. Our results indicated that sevoflurane postconditioning and TDZD-8 significantly reduced the cerebral infarction area, suppressed cell apoptosis, and improved mitochondrial integrity in zebrafish subjected to H/R. Furthermore, sevoflurane postconditioning and TDZD-8 elevated the ratios of p-Akt/Akt and p-GSK-3ß/GSK-3ß. However, the neuroprotective effect of sevoflurane postconditioning was effectively abolished upon suppression of MAP2 expression. In conclusion, sevoflurane postconditioning ameliorated cerebral H/R injury and facilitated the restoration of neurobehavioral function through the activation of Akt/GSK-3ß pathway and promotion of MAP2 expression.