title: Stress-induced bystander signaling as a possible factor contributing to neuronal excitability and seizure generation/epileptogenesis.
abstract: We hypothesize that cell stress-caused bystander signaling induced by certain exogenous and endogenous stressors, such as ionizing radiation exposure, chemicals, tumor, or senescent cells, might contribute to neuronal excitability and synchronization, specifically to initiation of hyperexcitability, excessive synchronization and seizure generation in epileptic brain/epileptogenesis. It is suggested that bystanderly induced interconnected variations in cytosolic Ca(2+), cytokines, and reactive oxygen/nitrogen species, and in activity of mitogen-activated protein kinases and nuclear factor κB pathways might affect neurotransmitter system, neuronal receptors and ion channels implicated in seizure generation/epileptogenesis, or modulate expression of genes associated with epileptogenesis. The mechanism suggested may, at least partly, explain the emerging evidence of association between exposures to low-dose ionizing radiation and epileptogenesis. The bystander mechanism for the generation of epilepsy might constitute new potential molecular target for the design of antiepileptic drugs.
authors.affiliation: Laboratory of Biological Action of Low-Intensity Factors, Siberian Federal University, 79 Svobodny pr., 660041 Krasnoyarsk, Russia; Neuroinformatics Department, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands. Electronic address: v.09@mail.ru.
authors.forename: Vladimir E
authors.initials: VE
authors.lastname: Zakhvataev
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects; D001925:Brain Damage, Chronic / Q000209:etiology / Q000503:physiopathology; D024201:Bystander Effect / Q000502:physiology*; D020013:Calcium Signaling; D003344:Cortical Synchronization / Q000502:physiology*; D016207:Cytokines / Q000502:physiology; D004307:Dose-Response Relationship, Radiation; D004827:Epilepsy / Q000209:etiology / Q000503:physiopathology*; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D051379:Mice; D008959:Models, Neurological; D009369:Neoplasms / Q000150:complications / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011832:Radiation Injuries / Q000209:etiology / Q000503:physiopathology; D018788:Radioactive Hazard Release; D051381:Rats; D012640:Seizures / Q000139:chemically induced / Q000209:etiology / Q000503:physiopathology; D013312:Stress, Physiological; D059016:Tumor Microenvironment
chemical_list: D000970:Antineoplastic Agents; D016207:Cytokines; D047908:Intracellular Signaling Peptides and Proteins