Rifaximin Improves Spatial Learning and Memory Impairment in Rats with Liver Damage-Associated Neuroinflammation
Patients with non-alcoholic fatty liver disease (NAFLD) may show mild cognitive impairment. Neuroinflammation in the hippocampus mediates cognitive impairment in rat models of minimal hepatic encephalopathy (MHE). Treatment with rifaximin reverses cognitive impairment in a large proportion of cirrho...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-05-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/10/6/1263 |
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| author | Paola Leone Gergana Mincheva Tiziano Balzano Michele Malaguarnera Vicente Felipo Marta Llansola |
| author_facet | Paola Leone Gergana Mincheva Tiziano Balzano Michele Malaguarnera Vicente Felipo Marta Llansola |
| author_sort | Paola Leone |
| collection | DOAJ |
| description | Patients with non-alcoholic fatty liver disease (NAFLD) may show mild cognitive impairment. Neuroinflammation in the hippocampus mediates cognitive impairment in rat models of minimal hepatic encephalopathy (MHE). Treatment with rifaximin reverses cognitive impairment in a large proportion of cirrhotic patients with MHE. However, the underlying mechanisms remain unclear. The aims of this work were to assess if rats with mild liver damage, as a model of NAFLD, show neuroinflammation in the hippocampus and impaired cognitive function, if treatment with rifaximin reverses it, and to study the underlying mechanisms. Mild liver damage was induced with carbon-tetrachloride. Infiltration of immune cells, glial activation, and cytokine expression, as well as glutamate receptors expression in the hippocampus and cognitive function were assessed. We assessed the effects of daily treatment with rifaximin on the alterations showed by these rats. Rats with mild liver damage showed hippocampal neuroinflammation, reduced membrane expression of glutamate N-methyl-D-aspartate (NMDA) receptor subunits, and impaired spatial memory. Increased C-C Motif Chemokine Ligand 2 (CCL2), infiltration of monocytes, microglia activation, and increased tumor necrosis factor α (TNFα) were reversed by rifaximin, that normalized NMDA receptor expression and improved spatial memory. Thus, rifaximin reduces neuroinflammation and improves cognitive function in rats with mild liver damage, being a promising therapy for patients with NAFLD showing mild cognitive impairment. |
| first_indexed | 2024-03-10T00:21:34Z |
| format | Article |
| id | doaj.art-2bcde08e9aac429c97c9d15e1a6e1403 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T00:21:34Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-2bcde08e9aac429c97c9d15e1a6e14032023-11-23T15:41:46ZengMDPI AGBiomedicines2227-90592022-05-01106126310.3390/biomedicines10061263Rifaximin Improves Spatial Learning and Memory Impairment in Rats with Liver Damage-Associated NeuroinflammationPaola Leone0Gergana Mincheva1Tiziano Balzano2Michele Malaguarnera3Vicente Felipo4Marta Llansola5Mar Lab Department of Neuroscience, NYU Grossman School of Medicine Science Building, New York, NY 10016, USALaboratory of Neurobiology, Centro de Investigación Príncipe Felipe, 46012 Valencia, SpainCentro Integral de Neurociencias, A.C. HM Hospital Universitario Puerta del Sur CINAC, 28938 Madrid, SpainDepartment of Psychobiology, Facultad de Psicología, Universitat de Valencia, 46010 Valencia, SpainLaboratory of Neurobiology, Centro de Investigación Príncipe Felipe, 46012 Valencia, SpainLaboratory of Neurobiology, Centro de Investigación Príncipe Felipe, 46012 Valencia, SpainPatients with non-alcoholic fatty liver disease (NAFLD) may show mild cognitive impairment. Neuroinflammation in the hippocampus mediates cognitive impairment in rat models of minimal hepatic encephalopathy (MHE). Treatment with rifaximin reverses cognitive impairment in a large proportion of cirrhotic patients with MHE. However, the underlying mechanisms remain unclear. The aims of this work were to assess if rats with mild liver damage, as a model of NAFLD, show neuroinflammation in the hippocampus and impaired cognitive function, if treatment with rifaximin reverses it, and to study the underlying mechanisms. Mild liver damage was induced with carbon-tetrachloride. Infiltration of immune cells, glial activation, and cytokine expression, as well as glutamate receptors expression in the hippocampus and cognitive function were assessed. We assessed the effects of daily treatment with rifaximin on the alterations showed by these rats. Rats with mild liver damage showed hippocampal neuroinflammation, reduced membrane expression of glutamate N-methyl-D-aspartate (NMDA) receptor subunits, and impaired spatial memory. Increased C-C Motif Chemokine Ligand 2 (CCL2), infiltration of monocytes, microglia activation, and increased tumor necrosis factor α (TNFα) were reversed by rifaximin, that normalized NMDA receptor expression and improved spatial memory. Thus, rifaximin reduces neuroinflammation and improves cognitive function in rats with mild liver damage, being a promising therapy for patients with NAFLD showing mild cognitive impairment.https://www.mdpi.com/2227-9059/10/6/1263hepatic encephalopathymild liver damagerifaximinmicrogliaNMDA receptorspatial learning and memory |
| spellingShingle | Paola Leone Gergana Mincheva Tiziano Balzano Michele Malaguarnera Vicente Felipo Marta Llansola Rifaximin Improves Spatial Learning and Memory Impairment in Rats with Liver Damage-Associated Neuroinflammation Biomedicines hepatic encephalopathy mild liver damage rifaximin microglia NMDA receptor spatial learning and memory |
| title | Rifaximin Improves Spatial Learning and Memory Impairment in Rats with Liver Damage-Associated Neuroinflammation |
| title_full | Rifaximin Improves Spatial Learning and Memory Impairment in Rats with Liver Damage-Associated Neuroinflammation |
| title_fullStr | Rifaximin Improves Spatial Learning and Memory Impairment in Rats with Liver Damage-Associated Neuroinflammation |
| title_full_unstemmed | Rifaximin Improves Spatial Learning and Memory Impairment in Rats with Liver Damage-Associated Neuroinflammation |
| title_short | Rifaximin Improves Spatial Learning and Memory Impairment in Rats with Liver Damage-Associated Neuroinflammation |
| title_sort | rifaximin improves spatial learning and memory impairment in rats with liver damage associated neuroinflammation |
| topic | hepatic encephalopathy mild liver damage rifaximin microglia NMDA receptor spatial learning and memory |
| url | https://www.mdpi.com/2227-9059/10/6/1263 |
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