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Differential Effect of Repeated Lipopolysaccharide Treatment and Aging on Hippocampal Function and Biomarkers of Hippocampal Senescence

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Abstract

Markers of brain aging and cognitive decline are thought to be influenced by peripheral inflammation. This study compared the effects of repeated lipopolysaccharide (LPS) treatment in young rats to age-related changes in hippocampal-dependent cognition and transcription. Young Fischer 344 X Brown Norway hybrid rats were given intraperitoneal injections once a week for 7 weeks with either LPS or vehicle. Older rats received a similar injection schedule of vehicle. Old vehicle and young LPS rats exhibited a delay-dependent impairment in spatial memory. Further, LPS treatment reduced the hippocampal CA3–CA1 synaptic response. RNA sequencing, performed on CA1, indicated an increase in genes linked to neuroinflammation in old vehicle and young LPS animals. In contrast to an age-related decrease in transcription of synaptic genes, young LPS animals exhibited increased expression of genes that support the growth and maintenance of synapses. We suggest that the increased expression of genes for growth and maintenance of synapses in young animals represents neuronal resilience/recovery in response to acute systemic inflammation. Thus, the results indicate that repeated LPS treatment does not completely recapitulate the aging phenotype for synaptic function, possibly due to the chronic nature of systemic inflammation in aging and resilience of young animals to acute treatments.

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Acknowledgments

Special thanks to Nick Sarantos, Sophia Eikenberry, and Valentina Lavieri-Sosa for their assistance in animal handling and behavior assessment.

Funding

This study was financially supported by the National Institute of Aging grants R01AG037984, R37AG036800, R01049711, and R01052258 and the Evelyn F. McKnight Brain Research Foundation. This work was partially supported by the University of Florida Claude D Pepper Older American Independence Center (P30-AG028740). Authors also received financial support from the National High Magnetic Field Laboratory’s Advanced Magnetic Resonance Imaging & Spectroscopy (AMRIS) Facility (National Science Foundation Cooperative Agreement No. DMR-1157490 and the State of Florida).

Author information

Authors and Affiliations

  1. Department of Medicine, Division of General Medicine and Geriatrics, Emory University School of Medicine, Atlanta, GA, USA

    Jolie Barter

  2. Department of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, FL, 32610-0244, USA

    Ashok Kumar, Asha Rani, Marcelo Febo & Thomas C. Foster

  3. Department of Neurobiology and Behavior, Center for Learning and Memory, University of California, Irvine, CA, 92697, USA

    Luis M Colon-Perez

  4. Department of Psychiatry, McKnight Brain Institute, University of Florida, Gainesville, FL, USA

    Marcelo Febo

  5. Center for Addiction Research and Education, University of Florida, Gainesville, FL, 32611, USA

    Marcelo Febo

  6. Genetics and Genomics Program, University of Florida, Gainesville, 32611, FL, USA

    Thomas C. Foster

Authors
  1. Jolie Barter
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  2. Ashok Kumar
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  3. Asha Rani
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  4. Luis M Colon-Perez
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  5. Marcelo Febo
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  6. Thomas C. Foster
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Corresponding author

Correspondence to Thomas C. Foster.

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All procedures involving animals were approved by the Institutional Animal Care and Use Committee at the University of Florida and were in agreement with guidelines recognized by the U.S. Public Health Service Policy on Humane Care and Use of Laboratory Animals.

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The authors declare that they have no competing interests.

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Barter, J., Kumar, A., Rani, A. et al. Differential Effect of Repeated Lipopolysaccharide Treatment and Aging on Hippocampal Function and Biomarkers of Hippocampal Senescence. Mol Neurobiol 57, 4045–4059 (2020). https://doi.org/10.1007/s12035-020-02008-y

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  • DOI: https://doi.org/10.1007/s12035-020-02008-y

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