α-Galactosylceramide modulates the brain’s inflammatory microenvironment to counteract learning and memory dysfunction in Aβ1–42 model mice

doi:10.5246/jcps.2024.12.080

Journal of Chinese Pharmaceutical Sciences ›› 2024, Vol. 33 ›› Issue (12): 1110-1117.DOI: 10.5246/jcps.2024.12.080

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α-Galactosylceramide modulates the brain’s inflammatory microenvironment to counteract learning and memory dysfunction in Aβ1–42 model mice

Guangchan Jing²^,^#, Jingting Kang¹^,^#, Chao Ji¹^,^*()

¹ National Demonstration Center for Experimental Basic Medical Education (Peking Union Medical College), Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing 100005, China
² Department of Traditional Chinese Medicine, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China

Received:2024-07-23 Revised:2024-08-15 Accepted:2024-09-28 Online:2025-01-07 Published:2025-01-06
Contact: Chao Ji
About author:
^# Guangchan Jing and Jingting Kang contributed equally to this work.
Supported by:
National Natural Science Foundation of China (Grant No. 81100801).

Abstract

Abstract:

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder affecting the elderly. Among its pathological mechanisms, neuroinflammation triggered by amyloid-β (Aβ) aggregation is considered a key contributor. Alternatively activated (M2) macrophages and microglia have been shown to play a pivotal role in curbing neuroinflammation, thereby offering neuroprotective effects in neurodegenerative diseases. In the present study, we explored the therapeutic potential of α-galactosylceramide (α-Galcer) in enhancing learning and memory functions in AD model mice while delving into its underlying mechanisms. Our findings demonstrated that α-Galcer administration lowered the interferon regulatory factor (IRF)5/IRF4 ratio, leading to a higher proportion of M2 microglia and macrophages. These beneficial effects were achieved by modulating the expression of inflammation-related cytokines in the brains of AD model mice, thereby accelerating the resolution of neuroinflammation and ultimately enhancing cognitive performance.

Key words: Alzheimer’s disease, α-Galcer, M2 microglia/macrophage, Neuroinflammation, Microglial polarization

Supporting:

Guangchan Jing, Jingting Kang, Chao Ji. α-Galactosylceramide modulates the brain’s inflammatory microenvironment to counteract learning and memory dysfunction in Aβ1–42 model mice[J]. Journal of Chinese Pharmaceutical Sciences, 2024, 33(12): 1110-1117.

Figures/Tables 6

References 15

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α-Galactosylceramide modulates the brain’s inflammatory microenvironment to counteract learning and memory dysfunction in Aβ1–42 model mice

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