AUTHOR=Qin Yu , Zhao Yan , Hu Xiao , Chen Xi , Jiang Yan-Ping , Jin Xue-Jun , Li Gao , Li Zhen-Hao , Yang Ji-Hong , Zhang Guo-Liang , Cui Su-Ying , Zhang Yong-He
TITLE=Ganoderma lucidum spore extract improves sleep disturbances in a rat model of sporadic Alzheimer’s disease
JOURNAL=Frontiers in Pharmacology
VOLUME=15
YEAR=2024
URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1390294
DOI=10.3389/fphar.2024.1390294
ISSN=1663-9812
ABSTRACT=Introduction:Ganoderma lucidum (G. lucidum, Lingzhi) has long been listed as a premium tonic that can be used to improve restlessness, insomnia, and forgetfulness. We previously reported that a rat model of sporadic Alzheimer’s disease (sAD) that was induced by an intracerebroventricular injection of streptozotocin (ICV-STZ) showed significant learning and cognitive deficits and sleep disturbances. Treatment with a G. lucidum spore extract with the sporoderm removed (RGLS) prevented learning and memory impairments in sAD model rats.
Method: The present study was conducted to further elucidate the preventive action of RGLS on sleep disturbances in sAD rats by EEG analysis, immunofluorescence staining, HPLC-MS/MS and Western blot.
Results: Treatment with 720 mg/kg RGLS for 14 days significantly improved the reduction of total sleep time, rapid eye movement (REM) sleep time, and non-REM sleep time in sAD rats. The novelty recognition experiment further confirmed that RGLS prevented cognitive impairments in sAD rats. We also found that RGLS inhibited the nuclear factor-κB (NF-κB)/Nod-like receptor family pyrin domain-containing 3 (NLRP3) inflammatory pathway in the medial prefrontal cortex (mPFC) in sAD rats and ameliorated the lower activity of γ-aminobutyric acid (GABA)-ergic neurons in the parabrachial nucleus (PBN).
Discussion: These results suggest that inhibiting the neuroinflammatory response in the mPFC may be a mechanism by which RGLS improves cognitive impairment. Additionally, improvements in PBN-GABAergic activity and the suppression of neuroinflammation in the mPFC in sAD rats might be a critical pathway to explain the preventive effects of RGLS on sleep disturbances in sAD.