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Spatial Training Ameliorates Long-Term Alzheimer's Disease-Like Pathological Deficits by Reducing NLRP3 Inflammasomes in PR5 Mice.

ABSTRACT: Recent studies have suggested that cognitive training could delay memory loss in Alzheimer's disease (AD). However, whether and how cognitive training produces long-term benefits remains unclear. Here, 10-month-old PR5 mice were spatially trained in a water maze for 4 consecutive weeks. The novel object recognition test (NORT), Western blots, Golgi staining, and ELISA were used to examine behavioral, biochemical, and pathological measures immediately after training and 3 months later. Immediately after training, we found that spatial training significantly improved cognitive performance; reduced tau neuropathology; increased the expression level of synaptophysin, PSD93, and PSD95 in the hippocampus; and increased the number of dendritic spines in PR5 mice. The expression levels of NLRP3, caspase-1, and interleukin (IL)-1?, which were significantly elevated in PR5 mice, were reversed by spatial training. Interestingly, these effects persisted 3 months later. To further detect the role of NLRP3 in spatial training, PR5/NLRP3-/- mice and PR5/NLRP3+/- mice were also used in our study. PR5/NLRP3-/- mice showed better cognitive performance than PR5 mice. After 1 week of spatial training, these changes (including those in expression levels of synaptophysin, PSD93, and PSD95; the number of dendritic spines; and caspase-1 and IL-1? content in PR5 mice) could be totally reversed in PR5/NLRP3-/- and PR5/NLRP3+/- mice. In addition, there was a positive correlation between NLRP3 content and the expression levels of caspase-1 and IL-1?. These results show an important role for the NLRP3/caspase-1/IL-1? axis in ameliorating the effect of spatial training on cognitive impairment in PR5 mice.

SUBMITTER: Ren QG

PROVIDER: S-EPMC6554388 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Spatial Training Ameliorates Long-Term Alzheimer's Disease-Like Pathological Deficits by Reducing NLRP3 Inflammasomes in PR5 Mice.

Ren Qing-Guo QG Gong Wei-Gang WG Zhou Hong H Shu Hao H Wang Yan-Juan YJ Zhang Zhi-Jun ZJ

Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics 20190401 2

Recent studies have suggested that cognitive training could delay memory loss in Alzheimer's disease (AD). However, whether and how cognitive training produces long-term benefits remains unclear. Here, 10-month-old PR5 mice were spatially trained in a water maze for 4 consecutive weeks. The novel object recognition test (NORT), Western blots, Golgi staining, and ELISA were used to examine behavioral, biochemical, and pathological measures immediately after training and 3 months later. Immediatel ...[more]

PMID: 30560481

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Project description:BackgroundThis study sought to explore the mechanism underlying the therapeutic effects of electroacupuncture (EA) on spatial memory deficits caused by surgery.MethodsHepatic apex resection was performed under propofol-based total intravenous anesthesia. Male Sprague-Dawley rats were subjected to EA treatment or EA + mitochondrial division inhibitor-1 (mdivi-1) treatment once a day for three consecutive days after surgery. The Morris water maze test was used to evaluate the spatial memory of the rats after surgery. Tissue from the hippocampus of each rat was frozen and used for transcriptomic and proteomic analyses to identify potential targets for EA treatment. Western blotting was used to confirm the protein expression levels. The levels of reactive oxygen species (ROS) and adenosine triphosphate (ATP) were detected using commercial kits. The rat mitochondria were then isolated, and the activity of mitochondrial complex V was assessed.ResultsEA attenuated surgery-induced spatial memory deficits on postoperative day 3, while these effects were reversed by treatment with the mdivi-1 (P<0.05). Ribonucleic acid (RNA)-sequencing revealed that EA upregulated multiple metabolic pathways and the phosphatidylinositol 3‑kinas/protein kinase B signaling pathway. The proteomic and western blotting results suggested that the EA treatment substantially downregulated coiled-coil-helix-coiled-coil-helix domain containing 3 (ChChd3) expression in the hippocampus. The EA treatment significantly increased the autophagy-related protein levels, including phosphatase and tensin homolog-induced kinase 1, Parkin, MAP1LC3 (LC3), and Beclin1, and inhibited the production of ROS and inflammatory cytokine interleukin-1β in the hippocampus (P<0.05).ConclusionsThese results suggest that EA ameliorates postoperative spatial memory deficits and protects hippocampus from oxidative stress and inflammation through enhanced autophagy in an animal model of perioperative neurocognitive disorders (PNDs).

Dataset Information

Spatial Training Ameliorates Long-Term Alzheimer's Disease-Like Pathological Deficits by Reducing NLRP3 Inflammasomes in PR5 Mice.

Publications

Spatial Training Ameliorates Long-Term Alzheimer's Disease-Like Pathological Deficits by Reducing NLRP3 Inflammasomes in PR5 Mice.

Similar Datasets

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