2. Academic Validation
  3. Corticosterone-mediated microglia activation affects dendritic spine plasticity and motor learning functions in minimal hepatic encephalopathy

Corticosterone-mediated microglia activation affects dendritic spine plasticity and motor learning functions in minimal hepatic encephalopathy

  • Brain Behav Immun. 2019 Nov;82:178-187. doi: 10.1016/j.bbi.2019.08.184.
Xiaoming Sun 1,  Rui Han 1,  Tong Cheng 1,  Yuhan Zheng 1,  Jia Xiao 2,  Kwok-Fai So 3,  Li Zhang 4
Affiliations

Affiliations

  • 1 Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, PR China.
  • 2 Laboratory of Neuroendocrinology, College of Life Sciences, Fujian Normal University, Fuzhou, PR China; Institute of Clinical Medicine, The First Affiliated Hospital of Jinan University, Guangzhou, PR China; School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
  • 3 Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, PR China; State Key Laboratory of Brain and Cognitive Science, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, PR China; Center for Brain Science and Brain-Inspired Intelligence, Guangdong-Hong Kong-Macau Greater Bay Area, Guangzhou, PR China. Electronic address: hrmaskf@hku.hk.
  • 4 Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan University, Guangzhou, PR China; Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, PR China; Center for Brain Science and Brain-Inspired Intelligence, Guangdong-Hong Kong-Macau Greater Bay Area, Guangzhou, PR China. Electronic address: zhangli@jnu.edu.cn.
PMID: 31437533 DOI: 10.1016/j.bbi.2019.08.184
Abstract

Minimal hepatic encephalopathy (MHE) is characterized as cognitive deficits including memory and learning dysfunctions after liver injuries or hepatic diseases. Our understandings of neurological mechanisms of MHE-associated cognitive syndromes, however, are far from complete. In the current study we generated a mouse MHE model by repetitive administrations of thioacetamide (TAA), which induced hyperammonemia plus elevated proinflammatory cytokines in both the general circulation and motor cortex. MHE mice presented prominent motor learning deficits, which were associated with excess dendritic spine pruning in the motor cortex under 2-photon in vivo microscopy. The pharmaceutical blockade of Glucocorticoid Receptor or suppression of its biosynthesis further rescued motor learning deficits and synaptic protein loss. Moreover, MHE mice presented microglial activation, which can be alleviated after glucocorticoid pathway inhibition. In sum, our data demonstrates corticosterone-induced microglial activation, synaptic over-pruning and motor learning impairments in MHE, providing new insights for MHE pathogenesis and potential targets of clinical interventions.

Keywords

Dendritic spine; Glucocorticoid hormone; Microglia; Minimal hepatic encephalopathy; Motor learning.

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