Oxytocin ameliorates cognitive impairments by attenuating excitation/inhibition imbalance of neurotransmitters acting on parvalbumin interneurons in a mouse model of sepsisassociated encephalopathy  

作　　者：Renqi Li Qiuting Zeng Muhuo Ji Yue Zhang Mingjie Mao Shanwu Feng Manlin Duan Zhiqiang Zhou 

机构地区：[1]Department of Anesthesiology,Jinling Clinical Medical College of Nanjing Medical University,Nanjing,Jiangsu 210002,China [2]Department of Anesthesiology,Women's Hospital of Nanjing Medical University,Nanjing Women and Children's Healthcare Hospital,Nanjing,Jiangsu 210004,China [3]Department of Anesthesiology,Zhongda Hospital,School of Medicine,Southeast University,Nanjing,Jiangsu 210009,China [4]Department of Anesthesiology,the Second Affiliated Hospital,Nanjing Medical University,Nanjing,Jiangsu 210011,China [5]Department of Anesthesiology,Jinling Hospital,School of Medicine,Nanjing University,Nanjing,Jiangsu 210002,China

出　　处：《Journal of Biomedical Research》2025年第2期132-145,共14页生物医学研究杂志(英文版)

基　　金：supported by grants from the general project of Nanjing Medical University Science and Technology Development Foundation (Grant No.NMUB20210112)。

摘　　要：Inflammation plays a crucial role in the initiation and progression of sepsis and induces alterations in brain neurotransmission, thereby contributing to the development of sepsis-associated encephalopathy(SAE).Parvalbumin(PV) interneurons are pivotal contributors to cognitive processes and have been implicated in various central nervous system dysfunctions, including SAE. Oxytocin, known for its ability to augment the firing rate of gamma-aminobutyric acid(GABA)-ergic interneurons and directly stimulate inhibitory interneurons to enhance the tonic inhibition of pyramidal neurons, has prompted an investigation into its potential therapeutic effects on cognitive dysfunction in SAE. In the current study, we administered intranasal oxytocin to SAE mice induced by lipopolysaccharide. Behavioral assessments, including open field, Y-maze, and fear conditioning, were used to evaluate cognitive performance. Golgi staining revealed hippocampal synaptic deterioration, local field potential recordings showed weakened gamma oscillations, and immunofluorescence staining demonstrated decreased PV expression in the cornu ammonis 1(CA1) region of the hippocampus following lipopolysaccharide treatment, all of which were alleviated by oxytocin administration. Furthermore, immunofluorescence staining of PV co-localization with vesicular glutamate transporter 1 or vesicular GABA transporter indicated a balanced excitation/inhibition effect of neurotransmitters on PV interneurons after oxytocin administration in the SAE mice, leading to an improved cognitive function. In conclusion, oxytocin treatment improved cognitive function by increasing the number of PV^(+) neurons in the hippocampal CA1 region, restoring the balance of excitatory/inhibitory synaptic transmission on PV interneurons, and enhancing hippocampal CA1 local field potential gamma oscillations. These findings suggest a potential mechanism underlying the beneficial effects of oxytocin in SAE.

关 键 词：excitation/inhibition balance OXYTOCIN cognitive sepsis-associated encephalopathy 

分 类 号：R747.9[医药卫生—神经病学与精神病学]