Growth arrest DNA damage-inducible protein 45 β (GADD45B) has been reported to be a regulatory factor for active DNA demethylation and is implicated in the modulation of synaptic plasticity and chronic stress-related psychopathological processes. However, its precise role and mechanism of action in stress susceptibility remain elusive. In this study, we found a significant reduction in GADD45B expression specifically in the ventral, but not the dorsal hippocampal CA1 (dCA1) of stress-susceptible mice. Furthermore, we demonstrated that GADD45B negatively regulates susceptibility to social stress and NMDA receptor-dependent long-term potentiation (LTP) in the ventral hippocampal CA1 (vCA1). Importantly, through pharmacological inhibition using the NMDA receptor antagonist MK801, we provided further evidence supporting the hypothesis that GADD45B potentially modulates susceptibility to social stress by influencing NMDA receptor-mediated LTP. Collectively, these results suggested that modulation of NMDA receptor-mediated synaptic plasticity is a pivotal mechanism underlying the regulation of susceptibility to social stress by GADD45B.
Animals ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors* ; CA1 Region, Hippocampal/drug effects* ; Male ; Stress, Psychological/physiopathology* ; Mice ; Neuronal Plasticity/drug effects* ; Long-Term Potentiation/drug effects* ; Mice, Inbred C57BL ; Antigens, Differentiation/metabolism* ; Dizocilpine Maleate/pharmacology* ; Excitatory Amino Acid Antagonists/pharmacology* ; GADD45 Proteins

Objective To investigate the association between levels of 23 urinary metals and lung function,and explore their does-response relationships in the general population of Wuhan province,China.Methods This was a cross-sectional study that enrolled volunteers from two communities of Wuhan between April and May 2011.All volunteers had resided in Wuhan for at least 5 years.Information from questionnaires and physical examinations were collected and lung function was assessed.Data from 2 540 volunteers were included.Urinary levels of 23 metals were measured by inductively coupled plasma mass spectrometry (ICP-MS).The relationship between urinary metals and lung function was analyzed with single and multiple regression models.Results The mean age of the study population was 52.8 years.Mean levels of urinary metals,after adjustment for creatinine,including cobalt,copper,zinc,nickel,antimony and barium were 0.02,0.68,23.80,0.20,0.10,0.34 and 0.26 μg/g creatinine,respectively.There were significant concentration-response relationships between increases in some urinary metals and reduced lung function.Single-metal regression models demonstrated that for each 1-unit increase in urinary levels of cobalt,lncopper,lnzinc,lnantimony,there was a reduction in forced vital capacity (FVC) of 0.091 L (95％CI:-0.155--0.027),0.101 L (95％CI:-0.178--0.025),0.094 L (95％CI:-0.172--0.027) and 0.1 18 L (95％ CI:-0.203--0.033),respectively.Each 1-unit-increase in urinary lncobalt,lnnickel,lnstrontium,lnantimony,lnthallium,lnlead was associated with a reductions in forced expiratory volume in 1 sec (FEV1)of 0.070 L (95％CI:-0.124--0.016),0.063 L (95％CI:-0.118--0.007),0.063 L (95％CI:-0.124--0.002),0.092 L (95％CI:-0.164--0.020),0.055 L (95％CI:-0.105--0.005),0.081 L (95％CI:-0.148--0.014),and 0.097 L (95％ CI:-0.151--0.042),respectively.With respect to metal co-exposure,FVC was significantly associated with elevated urinary levels of cobalt,Cu and Sb,with reductions of 0.126 L (95％CI:0.037-0.216) and 0.106 L (95％CI:0.021-0.192),respectively,while FEV1 was significantly associated with elevated urinary Co,Sb,Ba and Pb,with reductions of 0.067 L (95％CI:-0.129--0.005),0.142 L (95％ CI:-0.247--0.037),0.073 L (95％ CI:-0.142--0.003) and 0.104 L (95％ CI:-0.175--0.034),respectively.Conclusions Certain urinary metals were potentially associated,in a dose-dependent manner,with reduced lung function in the general population.Co-exposure to metals had stimulative and anti-stimulative effects on lung function.

Objective To investigate the association between levels of 23 urinary metals and lung function,and explore their does-response relationships in the general population of Wuhan province,China.Methods This was a cross-sectional study that enrolled volunteers from two communities of Wuhan between April and May 2011.All volunteers had resided in Wuhan for at least 5 years.Information from questionnaires and physical examinations were collected and lung function was assessed.Data from 2 540 volunteers were included.Urinary levels of 23 metals were measured by inductively coupled plasma mass spectrometry (ICP-MS).The relationship between urinary metals and lung function was analyzed with single and multiple regression models.Results The mean age of the study population was 52.8 years.Mean levels of urinary metals,after adjustment for creatinine,including cobalt,copper,zinc,nickel,antimony and barium were 0.02,0.68,23.80,0.20,0.10,0.34 and 0.26 μg/g creatinine,respectively.There were significant concentration-response relationships between increases in some urinary metals and reduced lung function.Single-metal regression models demonstrated that for each 1-unit increase in urinary levels of cobalt,lncopper,lnzinc,lnantimony,there was a reduction in forced vital capacity (FVC) of 0.091 L (95％CI:-0.155--0.027),0.101 L (95％CI:-0.178--0.025),0.094 L (95％CI:-0.172--0.027) and 0.1 18 L (95％ CI:-0.203--0.033),respectively.Each 1-unit-increase in urinary lncobalt,lnnickel,lnstrontium,lnantimony,lnthallium,lnlead was associated with a reductions in forced expiratory volume in 1 sec (FEV1)of 0.070 L (95％CI:-0.124--0.016),0.063 L (95％CI:-0.118--0.007),0.063 L (95％CI:-0.124--0.002),0.092 L (95％CI:-0.164--0.020),0.055 L (95％CI:-0.105--0.005),0.081 L (95％CI:-0.148--0.014),and 0.097 L (95％ CI:-0.151--0.042),respectively.With respect to metal co-exposure,FVC was significantly associated with elevated urinary levels of cobalt,Cu and Sb,with reductions of 0.126 L (95％CI:0.037-0.216) and 0.106 L (95％CI:0.021-0.192),respectively,while FEV1 was significantly associated with elevated urinary Co,Sb,Ba and Pb,with reductions of 0.067 L (95％CI:-0.129--0.005),0.142 L (95％ CI:-0.247--0.037),0.073 L (95％ CI:-0.142--0.003) and 0.104 L (95％ CI:-0.175--0.034),respectively.Conclusions Certain urinary metals were potentially associated,in a dose-dependent manner,with reduced lung function in the general population.Co-exposure to metals had stimulative and anti-stimulative effects on lung function.