title: Regulation of Physical Microglia-Neuron Interactions by Fractalkine Signaling after Status Epilepticus.
abstract: Microglia, the resident immune cells of the brain, perform elaborate surveillance in which they physically interact with neuronal elements. A novel form of microglia-neuron interaction named microglial process convergence (MPC) toward neuronal axons and dendrites has recently been described. However, the molecular regulators and pathological relevance of MPC have not been explored. Here, using high-resolution two-photon imagingin vivoandex vivo, we observed a dramatic increase in MPCs after kainic acid- or pilocarpine-induced experimental seizures that was reconstituted after glutamate treatment in slices from mice. Interestingly, a deficiency of the fractalkine receptor (CX3CR1) decreased MPCs, whereas fractalkine (CX3CL1) treatment increased MPCs, suggesting that fractalkine signaling is a critical regulator of these microglia-neuron interactions. Furthermore, we found that interleukin-1β was necessary and sufficient to trigger CX3CR1-dependent MPCs. Finally, we show that a deficiency in fractalkine signaling corresponds with increased seizure phenotypes. Together, our results identify the neuroglial CX3CL1-CX3CR1 communication axis as a modulator of potentially neuroprotective microglia-neuron physical interactions during conditions of neuronal hyperactivity.
authors.affiliation: Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ 08854; Department of Neurology, Mayo Clinic, Rochester, MN 55905.
authors.forename: Ukpong B
authors.identifier: 0000-0003-1840-6925
authors.initials: UB
authors.lastname: Eyo
authors.affiliation: Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ 08854; Department of Neurology, Mayo Clinic, Rochester, MN 55905.
authors.forename: Jiyun
authors.identifier: 0000-0002-9912-8930
authors.initials: J
authors.lastname: Peng
authors.affiliation: Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ 08854; Department of Neurology, Mayo Clinic, Rochester, MN 55905.
authors.forename: Madhuvika
authors.identifier: 0000-0002-0706-0730
authors.initials: M
authors.lastname: Murugan
authors.affiliation: Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ 08854; Department of Neurology, First Affiliated Hospital of Guangzhou Medical University Guangdong, 510120, China.
authors.forename: Mingshu
authors.identifier: 0000-0002-4362-8194
authors.initials: M
authors.lastname: Mo
authors.affiliation: Department of Cell Biology and Neuroscience, Rutgers University , Piscataway, NJ 08854.
authors.forename: Almin
authors.initials: A
authors.lastname: Lalani
authors.affiliation: Department of Cell Biology and Neuroscience, Rutgers University , Piscataway, NJ 08854.
authors.forename: Ping
authors.initials: P
authors.lastname: Xie
authors.affiliation: Department of Neurology, First Affiliated Hospital of Guangzhou Medical University Guangdong , 510120, China.
authors.forename: Pingyi
authors.initials: P
authors.lastname: Xu
authors.affiliation: Department of Cell Biology and Neuroscience, Rutgers University , Piscataway, NJ 08854.
authors.forename: David J
authors.identifier: 0000-0002-2678-4216
authors.initials: DJ
authors.lastname: Margolis
authors.affiliation: Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ 08854; Department of Neurology, Mayo Clinic, Rochester, MN 55905.
authors.forename: Long-Jun
authors.identifier: 0000-0001-8019-3380
authors.initials: LJ
authors.lastname: Wu
mesh_terms: D000818:Animals; D054428:Chemokine CX3CL1 / Q000378:metabolism*; D018690:Excitatory Amino Acid Agonists / Q000008:administration & dosage; D005260:Female; D018698:Glutamic Acid / Q000008:administration & dosage / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D007608:Kainic Acid; D008297:Male; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D000066829:Neuroprotection / Q000502:physiology; D010862:Pilocarpine; D023062:Receptors, Interleukin-8A / Q000235:genetics / Q000378:metabolism; D058925:Receptors, Purinergic P2Y12 / Q000235:genetics / Q000378:metabolism; D012640:Seizures / Q000378:metabolism / Q000473:pathology; D013226:Status Epilepticus / Q000378:metabolism* / Q000473:pathology; D046509:Tissue Culture Techniques
chemical_list: D054428:Chemokine CX3CL1; C515539:Cx3cl1 protein, mouse; D018690:Excitatory Amino Acid Agonists; C587672:IL1B protein, mouse; D053583:Interleukin-1beta; C548577:P2ry12 protein, mouse; D023062:Receptors, Interleukin-8A; D058925:Receptors, Purinergic P2Y12; D010862:Pilocarpine; D018698:Glutamic Acid; D007608:Kainic Acid
keywords: epilepsy; fractalkine; glutamate; interleukin-1β; microglia; seizure