title: Oxidative stress in synapse development and function.
abstract: Oxidative stress, caused by increased levels of reactive oxidative species (ROS), is considered a major contributor to the aging process. How oxidative stress may bring about changes to structures and function in the aging brain is poorly understood. Oxidative stress activates a number of cellular responses, including activation of the Jun-N-terminal kinase (JNK) pathway and autophagy. In addition to their pathological role, ROS also act as signaling molecules. ROS such as nitric oxide have a well-known role in learning and memory. In addition, activation of JNK and its transcriptional effector AP-1 are well-known mediators of synaptic function and growth. Both are essential mediators of physiological correlates of learning and memory such as long-term potentiation. JNK and AP-1 are potently activated and regulated by oxidative stress and mediate protective cellular responses such as autophagy. Recent work at the Drosophila neuromuscular junction implicates autophagy as a regulator of synaptic growth via activation of the JNK signaling pathway. We here outline a framework predicating oxidative stress as a major regulator of synaptic function and growth by the activation of JNK/AP-1 and autophagy. Such responses, we suggest, may underpin some forms of synaptic growth responses and synaptic aging.
authors.affiliation: Department of Biology, University of York, York, YO10 5DD, United Kingdom.
authors.forename: Valerie J
authors.initials: VJ
authors.lastname: Milton
authors.forename: Sean T
authors.initials: ST
authors.lastname: Sweeney
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001343:Autophagy / Q000502:physiology; D006801:Humans; D007858:Learning / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species