Glucocorticoid (GC), secreted by adrenal cortex, plays important roles in regulating many physiological functions, while chronic stress level of GC exposure has many adverse effects on the structure and function of hippocampal neurons, and is closely implicated to the deterioration of Alzheimer's disease (AD). Oxidative stress and neuroinflammation play an important role in the occurrence and development of AD. However, it is still unclear whether chronic GC exposure promotes beta-amyloid (Aβ) accumulation and neuronal injury by increasing oxidative stress and neuroinflammation. In this study, we investigated the effects of chronic GC exposure on NOX2-NLRP1 inflammasome activation and the protective effects of NLRP1-siRNA against GC-induced neuronal injury in primary hippocampal neurons of APP/PS1 mice. The results showed that chronic dexamethasone (DEX, 1 µM) exposure 72 h had no significant effect on the primary hippocampal neurons of WT mice, but significantly increased Aβ accumulation (2.17 ± 0.19 fold in APP group and 3.06 ± 0.49 fold in APP + DEX group over WT group) and neuronal injury in primary hippocampal neurons of APP/PS1 mice. Meanwhile, chronic DEX exposure significantly increased the levels of reactive oxygen species (ROS) production and IL-1β, and significantly up-regulated the expressions of NOX2- and NLRP1-related proteins and mRNAs in primary hippocampal neurons of APP/PS1 mice but not in WT mice. Moreover, inhibition of NLRP1 by NLRP1-siRNA treatment also significantly alleviated neuronal injury and Aβ accumulation (1.96 ± 0.11 fold in APP + DEX group and 0.25 ± 0.01 fold in APP + NLRP1-siRNA + DEX group over APP group), and down-regulated the expressions of APP, BACE1, NCSTN and p-TAU/TAU in chronic DEX-induced hippocampal neurons of APP/PS1 mice. The results suggest that chronic GC exposure can accelerate neuronal damage and Aβ production by activating oxidative stress and NLRP1 inflammasome in primary hippocampal neurons of APP/PS1 mice, resulting in deterioration of AD.And inhibition of NLRP1 inflammasome may be an important strategy in improving chronic GC-induced neuronal injury.
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http://dx.doi.org/10.1016/j.intimp.2022.108972 | DOI Listing |
Elife
January 2025
Department of Neurology, Baylor College of Medicine, Houston, United States.
variants in children with neurodevelopmental impairment are difficult to assess due to their heterogeneity and unclear pathogenic mechanisms. We describe a child with neonatal-onset epilepsy, developmental impairment of intermediate severity, and G256W heterozygosity. Analyzing prior KCNQ2 channel cryoelectron microscopy models revealed G256 as a node of an arch-shaped non-covalent bond network linking S5, the pore turret, and the ion path.
View Article and Find Full Text PDFMetab Brain Dis
January 2025
Xuzhou Engineering Research Center of Medical Genetics and Transformation, Department of Genetics, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China.
The widely used Radix Astragali (RA) has significant therapeutic effects on cognitive impairment (CI) caused by type 2 diabetes (T2DM). However, the effective active ingredients and the precise mechanism underly RA alleviation of T2DM-induced CI still require further study. In this study, we aim to elucidate whether and how jaranol, a key effective active ingredient in RA, influences CI in db/db mice.
View Article and Find Full Text PDFJ Ethnopharmacol
January 2025
Jiangxi University of Chinese Medicine, Nanchang, 330006, PR China; National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine, Nanchang, 330006, PR China. Electronic address:
Ethnopharmacological Relevance: Syringa oblata Lindl (ZDX) is a plant in the Oleaceae family that is the primary ingredient in the classic Tibetan medicine AKARU sinensis. The plant's stem is used as a medicine, and Tibetan doctors often use it as a sedative, a use with a history of nearly 100 years. Tibetan medicine mainly uses lilac to treat headache, forgetfulness, insomnia, irritability and other symptoms.
View Article and Find Full Text PDFCereb Cortex
January 2025
School of Life Science and Technology, Inner Mongolia University of Science & Technology, No. 7, Aerding Street, Kundulun District, Baotou 014010, China.
The nervous system is highly dependent on the supply of oxygen and nutrients, so when demand for oxygen exceeds its supply, hypoxia is induced. The hippocampus is very important in the nervous system. It has the ability to control human behavior, memory, emotion, and so on.
View Article and Find Full Text PDFNat Commun
January 2025
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Identifying cell types and brain regions critical for psychiatric disorders and brain traits is essential for targeted neurobiological research. By integrating genomic insights from genome-wide association studies with a comprehensive single-cell transcriptomic atlas of the adult human brain, we prioritized specific neuronal clusters significantly enriched for the SNP-heritabilities for schizophrenia, bipolar disorder, and major depressive disorder along with intelligence, education, and neuroticism. Extrapolation of cell-type results to brain regions reveals the whole-brain impact of schizophrenia genetic risk, with subregions in the hippocampus and amygdala exhibiting the most significant enrichment of SNP-heritability.
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