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Isolation and Flow Cytometric Analysis of Immune Cells from the Ischemic Mouse Brain
Published on: February 12, 2016
Gut microbiota from mice with cerebral ischemia-reperfusion injury affects the brain in healthy mice
Hongru Wang1,2, Shangjun Ren3, Hailing Lv4
1Department of Neurology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, Shandong, China.
Abstract:
Gut microorganisms can profoundly influence brain function in the host and their behavior. Since altered brain functional connectivity (FC) has been implicated in various cerebrovascular disorders, including cerebral ischemia-reperfusion (I/R) injury, we hypothesized that gut microbiota in mice with cerebral I/R injury would affect brain FC when transplanted into germ-free mice. Metagenomic analysis of germ-free male C57BL/6J mice colonized with microbiota from mice with and without cerebral I/R injury showed a clear distinction in microbiota composition between mice colonized with control and I/R microbiota. The I/R microbiota-colonized mice showed decreased FC in the cingulate cortex, hippocampus, and thalamus, and exhibited increased anxiety as well as diminished spatial learning and memory and short-term object recognition memory. I/R microbiota-colonized mice also had significantly reduced dendritic spine density and synaptic protein levels and exhibited increased hippocampal inflammation. These results indicate that gut microbiota components from mice with cerebral I/R injury can alter animal behavior, brain functional connectivity, hippocampal neuronal plasticity, and neuroinflammation. Moreover, they increase our understanding of the mechanisms through which the gut microbiome contributes to the pathobiology of cerebrovascular diseases.
Insights
Gut microbes from mice with cerebral ischemia-reperfusion injury altered brain connectivity and behavior in germ-free mice. This suggests the gut microbiome influences cerebrovascular disease pathology.
Area of Science:
- Neuroscience
- Microbiology
- Gastroenterology
Background:
- Altered brain functional connectivity (FC) is linked to cerebrovascular disorders like cerebral ischemia-reperfusion (I/R) injury.
- The gut microbiome's influence on brain function and behavior is increasingly recognized.
Purpose of the Study:
- To investigate if gut microbiota from mice with cerebral I/R injury impacts brain FC and behavior when transplanted into germ-free mice.
- To explore the underlying mechanisms, including neuronal plasticity and neuroinflammation.
Main Methods:
- Metagenomic analysis of gut microbiota composition.
- Colonization of germ-free mice with microbiota from control and I/R-injured mice.
- Assessment of brain FC, behavior (anxiety, spatial memory), dendritic spine density, synaptic protein levels, and hippocampal inflammation.
Main Results:
- Distinct gut microbiota compositions were observed between control and I/R microbiota groups.
- I/R microbiota colonization led to decreased FC in the cingulate cortex, hippocampus, and thalamus.
- I/R microbiota-colonized mice exhibited increased anxiety, impaired learning/memory, reduced synaptic density, and heightened hippocampal inflammation.
Conclusions:
- Gut microbiota from cerebral I/R injury models can negatively affect host behavior, brain connectivity, and neuronal plasticity.
- These findings highlight the gut microbiome's role in the pathobiology of cerebrovascular diseases and neuroinflammation.
