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Comparative Study Journal Article Epublish 53 citations

PubMed: 33407625 DOI: 10.1186/s12974-020-02054-2

Comparisons of neuroinflammation, microglial activation, and degeneration of the locus coeruleus-norepinephrine system in APP/PS1 and aging mice.

J Neuroinflammation 18(1):10

Authors: Song Cao, Daniel W Fisher, Guadalupe Rodriguez, Tian Yu, Hongxin Dong

Affiliations

  • Department of Pain Medicine, Affiliated Hospital of Zunyi Medical University, 149 Dalian Street, Zunyi, 563000, Guizhou, China. Guizhou Key Lab of Anesthesia and Organ Protection, Affiliated Hospital of Zunyi Medical University, 6 West Xuefu Street, Zunyi, 563002, Guizhou, China. Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Chicago, IL, 60611, USA.
  • Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Chicago, IL, 60611, USA.
  • Department of Psychiatry and Behavioral Sciences, University of Washington Medical Center, 1959 NE Pacific St, Seattle, WA, 98195, USA.
  • Guizhou Key Lab of Anesthesia and Organ Protection, Affiliated Hospital of Zunyi Medical University, 6 West Xuefu Street, Zunyi, 563002, Guizhou, China.
  • Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Chicago, IL, 60611, USA.

Abstract

BACKGROUND

The role of microglia in Alzheimer's disease (AD) pathogenesis is becoming increasingly important, as activation of these cell types likely contributes to both pathological and protective processes associated with all phases of the disease. During early AD pathogenesis, one of the first areas of degeneration is the locus coeruleus (LC), which provides broad innervation of the central nervous system and facilitates norepinephrine (NE) transmission. Though the LC-NE is likely to influence microglial dynamics, it is unclear how these systems change with AD compared to otherwise healthy aging.

METHODS

In this study, we evaluated the dynamic changes of neuroinflammation and neurodegeneration in the LC-NE system in the brain and spinal cord of APP/PS1 mice and aged WT mice using immunofluorescence and ELISA.

RESULTS

Our results demonstrated increased expression of inflammatory cytokines and microglial activation observed in the cortex, hippocampus, and spinal cord of APP/PS1 compared to WT mice. LC-NE neuron and fiber loss as well as reduced norepinephrine transporter (NET) expression was more evident in APP/PS1 mice, although NE levels were similar between 12-month-old APP/PS1 and WT mice. Notably, the degree of microglial activation, LC-NE nerve fiber loss, and NET reduction in the brain and spinal cord were more severe in 12-month-old APP/PS1 compared to 12- and 24-month-old WT mice.

CONCLUSION

These results suggest that elevated neuroinflammation and microglial activation in the brain and spinal cord of APP/PS1 mice correlate with significant degeneration of the LC-NE system.

MeSH

Microglia, Locus Coeruleus, Spinal Cord, Norepinephrine, Aging, Brain, Spine

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