Neuronal NADPH oxidase is required for neurite regeneration of Aplysia bag cell neurons

• Published in: Journal of neurochemistry Vol. 167; no. 4; pp. 505 - 519
• Main Authors: Alam, S M Sabbir, Watanabe, Yuichiro, Steeno, Brooke L, Dutta, Soumyajit, Szilagyi, Halie A, Wei, Alexander, Suter, Daniel M
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.11.2023
• Subjects: Actin; Actins; Animals; Aplysia; Cones; CYBB protein; Growth cones; Hydrogen peroxide; Injury prevention; Kinases; NAD(P)H oxidase; NADPH Oxidase 4; NADPH Oxidases - pharmacology; Nervous system; Neurites; Neurodegeneration; Neurogenesis; Neurons; Oxidase; Physiological effects; Protein-tyrosine kinase; Reactive Oxygen Species; Regeneration; Tyrosine; growth cone; neurite regeneration; NADPH oxidase; hydrogen peroxide; reactive oxygen species
• ISSN: 0022-3042; 1471-4159; 1471-4159
• DOI: 10.1111/jnc.15977

NADPH oxidase (Nox), a major source of reactive oxygen species (ROS), is involved in neurodegeneration after injury and disease. Nox is expressed in both neuronal and non-neuronal cells and contributes to an elevated ROS level after injury. Contrary to the well-known damaging effect of Nox-derived ROS in neurodegeneration, recently a physiological role of Nox in nervous system development including neurogenesis, neuronal polarity, and axonal growth has been revealed. Here, we tested a role for neuronal Nox in neurite regeneration following mechanical transection in cultured Aplysia bag cell neurons. Using a novel hydrogen peroxide (H O )-sensing dye, 5'-(p-borophenyl)-2'-pyridylthiazole pinacol ester (BPPT), we found that H O levels are elevated in regenerating growth cones following injury. Redistribution of Nox2 and p40 in the growth cone central domain suggests Nox2 activation after injury. Inhibiting Nox with the pan-Nox inhibitor celastrol reduced neurite regeneration rate. Pharmacological inhibition of Nox is correlated with reduced activation of Src2 tyrosine kinase and F-actin content in the growth cone. Taken together, these findings suggest that Nox-derived ROS regulate neurite regeneration following injury through Src2-mediated regulation of actin organization in Aplysia growth cones.