长时程增强
脉冲前抑制
海马结构
海马体
奶油
NMDA受体
神经科学
精神分裂症(面向对象编程)
记忆障碍
下调和上调
医学
受体
心理学
内科学
认知
化学
精神科
转录因子
基因
生物化学
作者
Yayan Luo,Yu Yang,Min-Ling Zhang,Ni Fan
标识
DOI:10.1016/j.jneuroim.2022.577998
摘要
Accumulating evidence suggests that some patients with schizophrenia have high production of autoantibodies against the N-methyl-d-aspartate receptor (NMDAR) subunit GluN1 and that these antibodies lead to cognitive impairment. However, the molecular mechanisms of the deficits seen in these patients are largely unknown. In the present study, we found that passive infusion of GluN1 antibody into the hippocampus of mice for 7 days led to decreased expression of GluN1, phosphor-Ser897-GluN1, and EphrinB2 receptor (EphB2R); deficits in long-term potentiation (LTP) and synaptic transmission in the hippocampal CA1 area; impairment in prepulse inhibition (PPI); and deterioration of recognition memory in novel object recognition test. We also found decreased expression of CaMKIIβ, ERK1/2, CREB, and NF-κB after 7 days of GluN1 antibody exposure, as was the phosphorylation of these signaling molecules. The decrease in GluN1 and phosphor-Ser897-GluN1 expression and the deficits in LTP, PPI, and recognition memory were ameliorated by CaMKIIβ overexpression. These results suggest that downregulation of CaMKIIβ-ERK1/2-CREB-NF-κB signaling is responsiable for GluN1 antibody-associated impairment in PPI and memory and that GluN1 antibody-induced NMDAR hypofunction is the underlying mechanism of this impairment. Our findings indicate possible strategies to ameliorate NMDAR antibody-associated cognitive impairment in neuropsychiatric disease. They also provide evidence that NMDAR hypofunction is an underlying mechanism for cognitive impairment in schizophrenia.
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