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

被引:159
作者
Birey, Fikri [1 ,2 ]
Kloc, Michelle [3 ]
Chavali, Manideep [1 ,4 ]
Hussein, Israa [1 ]
Wilson, Michael [1 ]
Christoffel, Daniel J. [5 ,6 ]
Chen, Tony [1 ]
Frohman, Michael A. [1 ]
Robinson, John K. [7 ]
Russo, Scott J. [5 ,6 ]
Maffei, Arianna [3 ]
Aguirre, Adan [1 ]
机构
[1] SUNY Stony Brook, Dept Pharmacol Sci, Stony Brook, NY 11794 USA
[2] SUNY Stony Brook, Grad Program Genet, Stony Brook, NY 11794 USA
[3] SUNY Stony Brook, Dept Neurobiol & Behav, Stony Brook, NY 11794 USA
[4] SUNY Stony Brook, Dept Mat Sci & Engn, Stony Brook, NY 11794 USA
[5] Mt Sinai Sch Med, Fishberg Dept Neurosci, New York, NY 10029 USA
[6] Mt Sinai Sch Med, Friedman Brain Inst, New York, NY 10029 USA
[7] SUNY Stony Brook, Dept Psychol, Stony Brook, NY 11794 USA
关键词
OLIGODENDROCYTE PRECURSOR CELLS; SOCIAL DEFEAT STRESS; PREFRONTAL CORTEX; PROGENITOR CELLS; GRAY-MATTER; ADULT BRAIN; SYNAPTIC PLASTICITY; ANXIETY DISORDERS; MOOD DISORDERS; ANIMAL-MODELS;
D O I
10.1016/j.neuron.2015.10.046
中图分类号
Q189 [神经科学];
学科分类号
071006 [神经生物学];
摘要
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.
引用
收藏
页码:941 / 956
页数:16
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