title: Genetic and Stress-Induced Loss of NG2 Glia Triggers Emergence of Depressive-like Behaviors through Reduced Secretion of FGF2.
abstract: NG2-expressing glia (NG2 glia) are a uniformly distributed and mitotically active pool of cells in the central nervous system (CNS). In addition to serving as progenitors of myelinating oligodendrocytes, NG2 glia might also fulfill physiological roles in CNS homeostasis, although the mechanistic nature of such roles remains unclear. Here, we report that ablation of NG2 glia in the prefrontal cortex (PFC) of the adult brain causes deficits in excitatory glutamatergic neurotransmission and astrocytic extracellular glutamate uptake and induces depressive-like behaviors in mice. We show in parallel that chronic social stress causes NG2 glia density to decrease in areas critical to Major Depressive Disorder (MDD) pathophysiology at the time of symptom emergence in stress-susceptible mice. Finally, we demonstrate that loss of NG2 glial secretion of fibroblast growth factor 2 (FGF2) suffices to induce the same behavioral deficits. Our findings outline a pathway and role for NG2 glia in CNS homeostasis and mood disorders.
authors.affiliation: Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794, USA; Graduate Program in Genetics, Stony Brook University, Stony Brook, NY 11794, USA.
authors.forename: Fikri
authors.initials: F
authors.lastname: Birey
authors.affiliation: Department of Neurobiology and Behavior, Stony Brook University, Stony Brook, NY 11794, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Kloc
authors.affiliation: Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794, USA; Department of Materials Science and Engineering, Stony Brook University, Stony Brook, NY 11794, USA.
authors.forename: Manideep
authors.initials: M
authors.lastname: Chavali
authors.affiliation: Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794, USA.
authors.forename: Israa
authors.initials: I
authors.lastname: Hussein
authors.affiliation: Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Wilson
authors.affiliation: Fishberg Department of Neuroscience and Friedman Brain Institute, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Christoffel
authors.affiliation: Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794, USA.
authors.forename: Tony
authors.initials: T
authors.lastname: Chen
authors.affiliation: Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Frohman
authors.affiliation: Department of Psychology, Stony Brook University, Stony Brook, NY 11794, USA.
authors.forename: John K
authors.initials: JK
authors.lastname: Robinson
authors.affiliation: Fishberg Department of Neuroscience and Friedman Brain Institute, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Russo
authors.affiliation: Department of Neurobiology and Behavior, Stony Brook University, Stony Brook, NY 11794, USA.
authors.forename: Arianna
authors.initials: A
authors.lastname: Maffei
authors.affiliation: Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794, USA. Electronic address: adan.aguirre@stonybrook.edu.
authors.forename: Adan
authors.initials: A
authors.lastname: Aguirre
mesh_terms: D027322:Amino Acid Transport System X-AG / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000941:Antigens / Q000235:genetics / Q000378:metabolism*; D003863:Depression / Q000209:etiology / Q000473:pathology*; D004167:Diphtheria Toxin / Q000008:administration & dosage; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000235:genetics; D005106:Exploratory Behavior / Q000502:physiology; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism*; D066257:Heparin-binding EGF-like Growth Factor / Q000235:genetics; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D017397:Prefrontal Cortex / Q000473:pathology*; D021381:Protein Transport / Q000187:drug effects / Q000235:genetics; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013315:Stress, Psychological / Q000503:physiopathology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D027322:Amino Acid Transport System X-AG; D000941:Antigens; D004167:Diphtheria Toxin; D016222:Fibroblast Growth Factor 2; D066257:Heparin-binding EGF-like Growth Factor; D010751:Phosphopyruvate Hydratase; D011509:Proteoglycans; D017470:Receptors, Glutamate; D000099216:Chondroitin Sulfate Proteoglycan 4