Corticosterone-mediated microglia activation affects dendritic spine plasticity and motor learning functions in minimal hepatic encephalopathy |
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| Affiliation: | 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;3. Institute of Clinical Medicine, The First Affiliated Hospital of Jinan University, Guangzhou, PR China;4. School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China;5. State Key Laboratory of Brain and Cognitive Science, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China;6. Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, PR China;7. Center for Brain Science and Brain-Inspired Intelligence, Guangdong-Hong Kong-Macau Greater Bay Area, Guangzhou, PR China;1. School of Biomedical Sciences and Pharmacy and the Priority Research Centre for Stroke and Brain Injury, University of Newcastle, Callaghan, NSW, Australia;2. Hunter Medical Research Institute, Newcastle, NSW, Australia;3. NHMRC Centre of Research Excellence Stroke Rehabilitation and Brain Recovery, Heidelberg, VIC, Australia;4. School of Electrical Engineering and Computer Science, University of Newcastle, Callaghan, NSW, Australia;1. Department of Neurology, Christian Doppler Klinik, Paracelsus Medical University, Salzburg, Austria;2. Department of Neurology, Franz Tappeiner Hospital, Merano, Italy;3. Department of Physiology, Medical University of Graz, Graz, Austria;4. Department of Neurological and Movement Sciences, Section of Clinical Neurology, University of Verona, Verona, Italy;1. Department of Anesthesiology, The Affiliated Hospital of Southwest Medical University, Luzhou, PR China;2. Department of Traditional Chinese Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, PR China;3. Department of Anesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, PR China |
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| 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. |
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| Keywords: | Minimal hepatic encephalopathy Dendritic spine Motor learning Microglia Glucocorticoid hormone |
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