Genetic and Stress-Induced Loss of NG2 Glia Triggers Emergence of Depressive-like Behaviors through Reduced Secretion of FGF2

Fikri Birey; Michelle Kloc; Manideep Chavali; Israa Hussein; Michael Wilson; Daniel J Christoffel; Tony Chen; Michael A Frohman; John K Robinson; Scott J Russo; Arianna Maffei; Adan Aguirre

doi:10.1016/j.neuron.2015.10.046

Genetic and Stress-Induced Loss of NG2 Glia Triggers Emergence of Depressive-like Behaviors through Reduced Secretion of FGF2

Neuron. 2015 Dec 2;88(5):941-956. doi: 10.1016/j.neuron.2015.10.046. Epub 2015 Nov 20.

Authors

Affiliations

¹ Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794, USA; Graduate Program in Genetics, Stony Brook University, Stony Brook, NY 11794, USA.
² Department of Neurobiology and Behavior, Stony Brook University, Stony Brook, NY 11794, USA.
³ 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.
⁴ Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794, USA.
⁵ Fishberg Department of Neuroscience and Friedman Brain Institute, Mount Sinai School of Medicine, New York, NY 10029, USA.
⁶ Department of Psychology, Stony Brook University, Stony Brook, NY 11794, USA.
⁷ Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794, USA. Electronic address: adan.aguirre@stonybrook.edu.

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.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Amino Acid Transport System X-AG / genetics
Amino Acid Transport System X-AG / metabolism
Animals
Antigens / genetics
Antigens / metabolism*
Depression / etiology
Depression / pathology*
Diphtheria Toxin / administration & dosage
Disease Models, Animal
Down-Regulation / genetics
Exploratory Behavior / physiology
Fibroblast Growth Factor 2 / genetics
Fibroblast Growth Factor 2 / metabolism*
Heparin-binding EGF-like Growth Factor / genetics
Humans
Membrane Potentials / drug effects
Membrane Potentials / genetics
Mice
Mice, Inbred C57BL
Mice, Transgenic
Neuroglia / metabolism*
Neurons / drug effects
Neurons / metabolism
Phosphopyruvate Hydratase / metabolism
Prefrontal Cortex / pathology*
Protein Transport / drug effects
Protein Transport / genetics
Proteoglycans / genetics
Proteoglycans / metabolism*
Receptors, Glutamate / genetics
Receptors, Glutamate / metabolism
Signal Transduction / drug effects
Signal Transduction / genetics
Stress, Psychological / physiopathology*
Synaptic Transmission / drug effects
Synaptic Transmission / genetics

Substances

Amino Acid Transport System X-AG
Antigens
Diphtheria Toxin
Heparin-binding EGF-like Growth Factor
Proteoglycans
Receptors, Glutamate
chondroitin sulfate proteoglycan 4
Fibroblast Growth Factor 2
Phosphopyruvate Hydratase

Abstract

Publication types

MeSH terms

Substances

Grants and funding