Neuroinflammaging underlies emotional disturbances and circadian rhythm disruption in young male senescence-accelerated mouse prone 8 mice

Naoki Ito; Hiroaki Takemoto; Ayana Hasegawa; Chika Sugiyama; Kengo Honma; Takayuki Nagai; Yoshinori Kobayashi; Hiroshi Odaguchi

doi:10.1016/j.exger.2020.111109

Neuroinflammaging underlies emotional disturbances and circadian rhythm disruption in young male senescence-accelerated mouse prone 8 mice

Exp Gerontol. 2020 Dec:142:111109. doi: 10.1016/j.exger.2020.111109. Epub 2020 Oct 16.

Authors

Naoki Ito¹, Hiroaki Takemoto², Ayana Hasegawa³, Chika Sugiyama⁴, Kengo Honma⁴, Takayuki Nagai⁵, Yoshinori Kobayashi⁶, Hiroshi Odaguchi⁷

Affiliations

¹ Oriental Medicine Research Center, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8642, Japan. Electronic address: ito-n@insti.kitasato-u.ac.
² School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8642, Japan.
³ Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8642, Japan.
⁴ Laboratory of Biochemical Pharmacology for Phytomedicines, Ōmura Satoshi Memorial Institute, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8642, Japan.
⁵ Oriental Medicine Research Center, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8642, Japan; Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8642, Japan; Laboratory of Biochemical Pharmacology for Phytomedicines, Ōmura Satoshi Memorial Institute, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8642, Japan.
⁶ Oriental Medicine Research Center, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8642, Japan; School of Pharmacy, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8642, Japan.
⁷ Oriental Medicine Research Center, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8642, Japan.

PMID: 33069781
DOI: 10.1016/j.exger.2020.111109

Abstract

Aging causes psychological dysfunction and neurodegeneration, and can lead to cognitive impairments. Although numerous studies have reported that neurodegeneration and subsequent cognitive impairments are involved in neuroinflammation, relationship between psychological disturbance and neuroinflammation with aging (neuroinflammaging) remains unclear. Here, to clarify the relationship, we examined whether neuroinflammaging affects emotional behaviors in senescence-accelerated mouse prone 8 (SAMP8) mice. Microglial inflammatory responses to a subsequent lipopolysaccharide (LPS) challenge were significantly enhanced in male SAMP8 mice relative to normal aging senescence-accelerated mouse resistant 1 (SAMR1) mice at 17 weeks, but not 8 weeks of age. LPS injection also significantly increased brain and systemic inflammation in SAMP8 mice at 17 weeks. In a battery of behavioral tests, SAMP8 mice at 17 weeks, but not 8 weeks, exhibited anxiety- and depression-like behaviors and circadian rhythm disruption. Taken together, SAMP8 mice at 17 weeks possess a brain microenvironment in which it is easier to trigger neuroinflammatory priming; this may lead to an emergence of anxiety- and depression-like behaviors and circadian rhythm disruption. These findings provide new insights into the temporal relationship between neuroinflammaging and emotion.

Keywords: Aging; Circadian rhythm; Depression; Microglia; Neuroinflammation; Senescence-accelerated mouse.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aging*
Animals
Anxiety
Brain
Circadian Rhythm*
Emotions
Male
Mice