title: Absence of CCL2 is sufficient to restore hippocampal neurogenesis following cranial irradiation.
abstract: Cranial irradiation for the treatment of brain tumors causes a delayed and progressive cognitive decline that is pronounced in young patients. Dysregulation of neural stem and progenitor cells is thought to contribute to these effects by altering early childhood brain development. Earlier work has shown that irradiation creates a chronic neuroinflammatory state that severely and selectively impairs postnatal and adult neurogenesis. Here we show that irradiation induces a transient non-classical cytokine response with selective upregulation of CCL2/monocyte chemoattractant protein-1 (MCP-1). Absence of CCL2 signaling in the hours after irradiation is alone sufficient to attenuate chronic microglia activation and allow the recovery of neurogenesis in the weeks following irradiation. This identifies CCL2 signaling as a potential clinical target for moderating the long-term defects in neural stem cell function following cranial radiation in children.
authors.affiliation: Stanford University, Institute for Stem Cell Biology and Regenerative Medicine, Stanford, CA 94305-5454, USA.
authors.forename: Star W
authors.initials: SW
authors.lastname: Lee
authors.forename: Ursula
authors.initials: U
authors.lastname: Haditsch
authors.forename: Branden J
authors.initials: BJ
authors.lastname: Cord
authors.forename: Raphael
authors.initials: R
authors.lastname: Guzman
authors.forename: Soo Jeong
authors.initials: SJ
authors.lastname: Kim
authors.forename: Chotima
authors.initials: C
authors.lastname: Boettcher
authors.forename: Josef
authors.initials: J
authors.lastname: Priller
authors.forename: Brandi K
authors.initials: BK
authors.lastname: Ormerod
authors.forename: Theo D
authors.initials: TD
authors.lastname: Palmer
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D016371:Cranial Irradiation; D006624:Hippocampus / Q000166:cytology* / Q000378:metabolism / Q000528:radiation effects; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D017628:Microglia / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D055495:Neurogenesis / Q000502:physiology* / Q000528:radiation effects; D009474:Neurons / Q000166:cytology* / Q000378:metabolism / Q000528:radiation effects
chemical_list: D018932:Chemokine CCL2