Amelioration of oxidative stress-induced phenotype loss of parvalbumin interneurons might contribute to the beneficial effects of environmental enrichment in a rat model of post-traumatic stress disorder.
Post-traumatic stress disorder (PTSD) is a common psychiatric disease following exposure to a severe traumatic event or physiological stress, which is characterized by anxiety- and depression-like behaviors and cognitive impairment. However, the underlying mechanisms remain elusive. Parvalbumin (PV) interneurons that are susceptible to oxidative stress are a subset of inhibitory GABAergic neurons regulating the excitability of pyramidal neurons, while dysfunction of PV interneurons is casually linked to many mental disorders including PTSD. We therefore hypothesized that environmental enrichment (EE), a method of enhanced cognitive, sensory and motor stimulation, can reverse the behavioral impairments by normalizing PV interneurons in a rat model of PTSD induced by inescapable foot shocks (IFS). Behavioral changes were determined by the open field, elevated plus maze, fear conditioning, and Morris water maze tests. The levels of nicotinamide adenosine dinucleotide phosphate (NADPH) oxidase 2 (NOX2), NOX4, PV, glutamic acid decarboxylase 67 (GAD-67), and 8-hydroxy-2-deoxyguanosine (8-OH-dG) in the hippocampus and prefrontal cortex were determined. Our results showed that in this PTSD model, rats displayed the anxiety-like behavior, enhanced fear learning behavior, and hippocampus- dependent spatial memory deficit, which were accompanied by the up-regulation of NOX2, 8-OH-dG, and down-regulation of PV and GAD-67. Notably, EE reversed all these abnormalities. These results suggest that restoration of PV interneurons by inhibiting oxidative stress in the hippocampus and prefrontal cortex might represent a mechanism through which EE reverses the behavioral impairments in a rat model of PTSD induced by IFS.
Department of Anesthesiology, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China; Department of Anesthesiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China.
Xiao R
XR
Sun
Department of Anesthesiology, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China; Department of Anesthesiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China.
Hui
H
Zhang
Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210093, China.
Hong T
HT
Zhao
Department of Anesthesiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China.
Mu H
MH
Ji
Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210093, China.
Hui H
HH
Li
Department of Anesthesiology, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China; Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210093, China.
Jing
J
Wu
Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210093, China. Electronic address: likuanyu@nju.edu.cn.
Kuan Y
KY
Li
Department of Anesthesiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China. Electronic address: yjyangjj@126.com.
Jian J
JJ
Yang
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D001007:Anxiety; D003214:Conditioning, Classical; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004195:Disease Models, Animal; D004597:Electroshock; D004777:Environment; D005239:Fear; D059330:GABAergic Neurons / Q000378:metabolism; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D007395:Interneurons / Q000378:metabolism*; D008297:Male; D018782:Maze Learning; D009249:NADP / Q000378:metabolism; D000074662:NADPH Oxidase 2 / Q000378:metabolism; D000074663:NADPH Oxidase 4 / Q000378:metabolism; D018384:Oxidative Stress; D010320:Parvalbumins / Q000378:metabolism*; D010641:Phenotype; D017397:Prefrontal Cortex / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species; D065852:Spatial Memory; D013313:Stress Disorders, Post-Traumatic / Q000378:metabolism* / Q000517:prevention & control / Q000523:psychology*
D010320:Parvalbumins; D017382:Reactive Oxygen Species; D009249:NADP; D000080242:8-Hydroxy-2'-Deoxyguanosine; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; C498911:Nox4 protein, rat; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; D003849:Deoxyguanosine
Environmental enrichment; Oxidative stress; Parvalbumin; Post-traumatic stress disorder