Differential Effect of Repeated Lipopolysaccharide Treatment and Aging on Hippocampal Function and Biomarkers of Hippoca
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Differential Effect of Repeated Lipopolysaccharide Treatment and Aging on Hippocampal Function and Biomarkers of Hippocampal Senescence Jolie Barter 1 & Ashok Kumar 2
&
Asha Rani 2 & Luis M Colon-Perez 3 & Marcelo Febo 2,4,5 & Thomas C. Foster 2,6
Received: 13 February 2020 / Accepted: 1 July 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
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. Keywords Inflammation . LPS . Hippocampus . Synaptic function . Cognition . NMDA receptor
Introduction It is well established that the immune system can modulate brain function. Understanding how inflammation alters neural Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12035-020-02008-y) contains supplementary material, which is available to authorized users. * Thomas C. Foster [email protected]; [email protected] 1
Department of Medicine, Division of General Medicine and Geriatrics, Emory University School of Medicine, Atlanta, GA, USA
2
Department of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, FL 32610-0244, USA
3
Department of Neurobiology and Behavior, Center for Learning and Memory, University of California, Irvine, CA 92697, USA
4
Department of Psychiatry, McKnight Brain Institute, University of Florida, Gainesville, FL, USA
5
Center for Addiction Research and Education, University of Florida, Gainesville, FL 32611, USA
6
Genetics and Genomics Program, University of Florida, Gainesville 32611, FL, USA
function is important for aging research, since aging is associated with reduced functional ability of the immune system [1] and elevated systemic markers of inflammation [2, 3]. In turn, e
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