title: Role of fractalkine-CX3CR1 pathway in seizure-induced microglial activation, neurodegeneration, and neuroblast production in the adult rat brain.
abstract: Temporal lobe seizures lead to an acute inflammatory response in the brain primarily characterized by activation of parenchymal microglial cells. Simultaneously, degeneration of pyramidal cells and interneurons is evident together with a seizure-induced increase in the production of new neurons within the dentate gyrus of the hippocampus. We have previously shown a negative correlation between the acute seizure-induced inflammation and the survival of newborn hippocampal neurons. Here, we aimed to evaluate the role of the fractalkine-CX3CR1 pathway for these acute events. Fractalkine is a chemokine expressed by both neurons and glia, while its receptor, CX3CR1 is primarily expressed on microglia. Electrically-induced partial status epilepticus (SE) was induced in adult rats through stereotaxically implanted electrodes in the hippocampus. Recombinant rat fractalkine or CX3CR1 antibody was infused intraventricularly during one week post-SE. A significant increase in the expression of CX3CR1, but not fractalkine, was observed in the dentate gyrus at one week. CX3CR1 antibody treatment resulted in a reduction in microglial activation, neurodegeneration, as well as neuroblast production. In contrast, fractalkine treatment had only minor effects. This study provides evidence for a role of the fractalkine-CX3CR1 signaling pathway in seizure-induced microglial activation and suggests that neuroblast production following seizures may partly occur as a result of microglial activation.
authors.affiliation: Inflammation and Stem Cell Therapy Group, Wallenberg Neuroscience Center, Division of Clinical Neurophysiology, Lund University, Sweden; Lund Epilepsy Center, Lund University, SE-221 84 Lund, Sweden.
authors.forename: Idrish
authors.initials: I
authors.lastname: Ali
authors.affiliation: Inflammation and Stem Cell Therapy Group, Wallenberg Neuroscience Center, Division of Clinical Neurophysiology, Lund University, Sweden; Lund Epilepsy Center, Lund University, SE-221 84 Lund, Sweden.
authors.forename: Deepti
authors.initials: D
authors.lastname: Chugh
authors.affiliation: Inflammation and Stem Cell Therapy Group, Wallenberg Neuroscience Center, Division of Clinical Neurophysiology, Lund University, Sweden; Lund Epilepsy Center, Lund University, SE-221 84 Lund, Sweden. Electronic address: Christine.Ekdahl_Clementson@med.lu.se.
authors.forename: Christine T
authors.initials: CT
authors.lastname: Ekdahl
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage; D000073883:CX3C Chemokine Receptor 1; D004195:Disease Models, Animal; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D058542:Implantable Neurostimulators; D008297:Male; D008822:Mice, Transgenic; D017628:Microglia / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D058953:Neural Stem Cells / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology; D017207:Rats, Sprague-Dawley; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000008:administration & dosage; D012640:Seizures / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D015398:Signal Transduction / Q000187:drug effects; D013226:Status Epilepticus / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors
chemical_list: D000906:Antibodies; D000073883:CX3C Chemokine Receptor 1; C516305:CX3CR1 protein, rat; C471885:Cx3cr1 protein, mouse; D019707:Receptors, Chemokine; D011994:Recombinant Proteins; D049452:Green Fluorescent Proteins
keywords: CX3CR1; Epilepsy; Fractalkine; Inflammation; Neurodegeneration; Neurogenesis