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Enduring and Sex-specific Changes in Hippocampal Gene Expression after a Subchronic Immune Challenge
Daria Tchessalova1, Natalie C Tronson1
1Department of Psychology and Neuroscience Graduate Program, University of Michigan, Ann Arbor, MI 48109, United States.
Neuroscience
|January 10, 2020
Summary
Illness can trigger lasting brain changes affecting memory and mood. This study reveals enduring, sex-specific gene expression alterations in the hippocampus following immune challenges, impacting cognitive function.
Area of Science:
- Neuroscience
- Immunology
- Genetics
Background:
- Major illnesses like sepsis can lead to persistent cognitive impairments, depression, and memory decline.
- Rodent models show lasting memory deficits after sepsis or immune challenge, even without ongoing neuroimmune activation.
Purpose of the Study:
- To identify brain mechanisms mediating persistent neural function changes after illness.
- To investigate enduring hippocampal gene expression alterations following a subchronic immune challenge using RNA-sequencing.
Main Methods:
- Utilized RNA-sequencing for a large-scale, unbiased analysis of hippocampal gene expression.
- Examined gene expression changes three months after a subchronic immune challenge in rodent models.
Main Results:
- Observed enduring gene expression dysregulation in the hippocampus three months post-immune challenge.
- Identified significant sex differences in the magnitude and type of gene expression changes.
- Males exhibited persistent changes in immune- and plasticity-related genes, while females showed fewer such changes but a distinct response to subsequent challenges.
Conclusions:
- Immune activation has long-lasting and sex-specific effects on hippocampal gene expression.
- These transcriptional changes may underlie persistent cognitive decline, affective disorders, and memory impairments after illness.
- Suggests enduring vulnerability to neurological and affective disorders due to illness-induced transcriptional dysregulation in the brain.
