scholarly journals Beneficial Effects of Sagacious Confucius’ Pillow Elixir on Cognitive Function in Senescence-Accelerated P8 Mice (SAMP8) via the NLRP3/Caspase-1 Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Zhitao Hou ◽  
Fengjin Li ◽  
Jing Chen ◽  
Yitian Liu ◽  
Changyuan He ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Function ◽  
Neuronal Degeneration ◽  
Blue Staining ◽  
Beneficial Effects ◽  
Caspase 1 ◽  
Pathogenic Factors ◽  
Hippocampal Ca1 ◽  
Underlying Mechanisms ◽  
Samp8 Mice

Sagacious Confucius’ Pillow Elixir (SCPE) is a traditional Chinese medicine that is mainly used for cognitive impairment in aging; however, the underlying mechanisms remain unclear. Aging is one of the most important pathogenic factors leading to inflammation and pyroptosis in the hippocampus, which may be a potential mechanism in elderly patients with cognitive impairment. Here, we examined whether SCPE could improve cognitive impairment in SAMP8 mice by reducing hippocampal inflammation and pyroptosis. Seven-month-old senescence-accelerated P8 mice (SAMP8) received SCPE (2.3 g/kg/day; 4.6 g/kg/day; 9.2 g/kg/day) for 28 days. Cognitive function and morphometric examinations were performed followed by water maze testing, hematoxylin-eosin staining, Congo red staining, toluidine blue staining, and TUNEL analysis of hippocampal CA1 and CA3 regions. Escape latency increased and times across platforms decreased in SAMP8 mice; however, both of them were normalized by SCPE after 28 days. Aging caused significant pyroptosis in hippocampal CA1 and CA3 regions, as evidenced by neuronal degeneration and necrosis, amyloid deposition, and decreased Nissl body amounts after cognitive impairment, which were greatly improved by SCPE. SCPE reduced serum IL-1β, IL-6, IL-18, and TNF-α levels and reduced hippocampal NLRP3, ASC, caspase-1, GSDM-D, IL-1β, IL-6, IL-18, and Aβ expression. Thus, SCPE exerts an antipyroptotic effect in aging, mainly by suppressing the NLRP3/caspase-1 signaling pathway.

scholarly journals Intranasal insulin rescues repeated anesthesia-induced deficits in synaptic plasticity and memory and prevents apoptosis in neonatal mice via mTORC1

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Patricia Soriano Roque ◽  
Mehdi Hooshmandi ◽  
Laura Neagu-Lund ◽  
Shelly Yin ◽  
Noosha Yousefpour ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Synaptic Plasticity ◽  
General Anesthesia ◽  
Preventive Treatment ◽  
Intranasal Insulin ◽  
Translational Repressor ◽  
Beneficial Effects ◽  
Underlying Mechanisms ◽  
Induced Apoptosis ◽  
Preclinical And Clinical Studies

AbstractLong-lasting cognitive impairment in juveniles undergoing repeated general anesthesia has been observed in numerous preclinical and clinical studies, yet, the underlying mechanisms remain unknown and no preventive treatment is available. We found that daily intranasal insulin administration to juvenile mice for 7 days prior to repeated isoflurane anesthesia rescues deficits in hippocampus-dependent memory and synaptic plasticity in adulthood. Moreover, intranasal insulin prevented anesthesia-induced apoptosis of hippocampal cells, which is thought to underlie cognitive impairment. Inhibition of the mechanistic target of rapamycin complex 1 (mTORC1), a major intracellular effector of insulin receptor, blocked the beneficial effects of intranasal insulin on anesthesia-induced apoptosis. Consistent with this finding, mice lacking mTORC1 downstream translational repressor 4E-BP2 showed no induction of repeated anesthesia-induced apoptosis. Our study demonstrates that intranasal insulin prevents general anesthesia-induced apoptosis of hippocampal cells, and deficits in synaptic plasticity and memory, and suggests that the rescue effect is mediated via mTORC1/4E-BP2 signaling.

scholarly journals Probiotics Fermentation Technology, a Novel Kefir Product, Ameliorates Cognitive Impairment in Streptozotocin-Induced Sporadic Alzheimer’s Disease in Mice

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Nesrine S. El Sayed ◽  
Esraa A. Kandil ◽  
Mamdooh H. Ghoneum
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Gut Microbiota ◽  
Neuronal Degeneration ◽  
Amyloid Plaque ◽  
Dependent Manner ◽  
Insulin Degrading Enzyme ◽  
Beneficial Effects ◽  
Fermentation Technology

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by cognitive impairment. Gut microbiota dysfunction (dysbiosis) is implicated in the pathology of AD and is associated with several detrimental consequences, including neurotransmitter depletion, oxidative stress, inflammation, apoptosis, and insulin resistance, which all contribute to the onset of AD. The objective of this study was to assess the effectiveness of Probiotics Fermentation Technology (PFT), a kefir product, in alleviating AD symptoms via regulation of the gut microbiota using a streptozotocin- (STZ-) induced AD mouse model and to compare its activity with simvastatin, which has been proven to effectively treat AD. Mice received one intracerebroventricular injection of STZ (3 mg/kg). PFT (100, 300, 600 mg/kg) and simvastatin (20 mg/kg) were administered orally for 3 weeks. PFT supplementation mitigated STZ-induced neuronal degeneration in the cortex and hippocampus, restored hippocampal acetylcholine levels, and improved cognition in a dose-dependent manner. These effects were accompanied by reductions in oxidative damage, proinflammatory cytokine expression, apoptosis, and tau hyperphosphorylation. Moreover, PFT hindered amyloid plaque accumulation via the enhancement of insulin-degrading enzyme. These beneficial effects were comparable to those produced by simvastatin. The results suggest that PFT can alleviate AD symptoms by regulating the gut microbiota and by inhibiting AD-related pathological events.

scholarly journals A Novel Mechanism of Mesenchymal Stromal Cell-Mediated Protection against Sepsis: Restricting Inflammasome Activation in Macrophages by Increasing Mitophagy and Decreasing Mitochondrial ROS

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Shuang Li ◽  
Hao Wu ◽  
Dong Han ◽  
Sai Ma ◽  
Wensi Fan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Nlrp3 Inflammasome ◽  
Therapeutic Potential ◽  
Cecal Ligation ◽  
Inflammasome Activation ◽  
Beneficial Effects ◽  
Caspase 1 ◽  
Mitochondrial Ros ◽  
Nlrp3 Inflammasome Activation ◽  
Underlying Mechanisms

Sepsis, a systemic inflammatory response to infection, is the leading cause of death in the intensive care unit (ICU). Previous studies indicated that mesenchymal stromal cells (MSCs) might have therapeutic potential against sepsis. The current study was designed to investigate the effects of MSCs on sepsis and the underlying mechanisms focusing on inflammasome activation in macrophages. The results demonstrated that the bone marrow-derived mesenchymal stem cells (BMSCs) significantly increased the survival rate and organ function in cecal ligation and puncture (CLP) mice compared with the control-grouped mice. BMSCs significantly restricted NLRP3 inflammasome activation, suppressed the generation of mitochondrial ROS, and decreased caspase-1 and IL-1β activation when cocultured with bone marrow-derived macrophages (BMDMs), the effects of which could be abolished by Mito-TEMPO. Furthermore, the expression levels of caspase-1, IL-1β, and IL-18 in BMDMs were elevated after treatment with mitophagy inhibitor 3-MA. Thus, BMSCs exert beneficial effects on inhibiting NLRP3 inflammasome activation in macrophages primarily via both enhancing mitophagy and decreasing mitochondrial ROS. These findings suggest that restricting inflammasome activation in macrophages by increasing mitophagy and decreasing mitochondrial ROS might be a crucial mechanism for MSCs to combat sepsis.

scholarly journals Short-term resistance exercise inhibits neuroinflammation and attenuates neuropathological changes in 3xTg Alzheimer’s disease mice

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Yan Liu ◽  
John Man Tak Chu ◽  
Tim Yan ◽  
Yan Zhang ◽  
Ying Chen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Cognitive Function ◽  
Resistance Training ◽  
Resistance Exercise ◽  
The Elderly ◽  
Short Term ◽  
Neuroprotective Effects ◽  
Beneficial Effects

Abstract Background Both human and animal studies have shown beneficial effects of physical exercise on brain health but most tend to be based on aerobic rather than resistance type regimes. Resistance exercise has the advantage of improving both muscular and cardiovascular function, both of which can benefit the frail and the elderly. However, the neuroprotective effects of resistance training in cognitive impairment are not well characterized. Methods We evaluated whether short-term resistant training could improve cognitive function and pathological changes in mice with pre-existing cognitive impairment. Nine-month-old 3xTg mouse underwent a resistance training protocol of climbing up a 1-m ladder with a progressively heavier weight loading. Results Compared with sedentary counterparts, resistance training improved cognitive performance and reduced neuropathological and neuroinflammatory changes in the frontal cortex and hippocampus of mice. In line with these results, inhibition of pro-inflammatory intracellular pathways was also demonstrated. Conclusions Short-term resistance training improved cognitive function in 3xTg mice, and conferred beneficial effects on neuroinflammation, amyloid and tau pathology, as well as synaptic plasticity. Resistance training may represent an alternative exercise strategy for delaying disease progression in Alzheimer’s disease.

scholarly journals Long-Term Walnut Oligopeptides Prevents Memory Loss in Aged SAMP8 Mice by Decreasing Oxidative Stress and Down-rRgulating the PI3K/Akt Signaling Pathway in Hippocampus

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 92-92 ◽  
Author(s):  
Meihong Xu ◽  
Qian Du ◽  
Yuntao Hao ◽  
Rui Fan ◽  
Yong Li
Keyword(s):  
Signaling Pathway ◽  
Memory Loss ◽  
Optimal Dose ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Memory Ability ◽  
Beneficial Effects ◽  
Funding Sources ◽  
Underlying Mechanisms ◽  
Samp8 Mice

Abstract Objectives Walnut Oligopeptides (WOPs), the effective component of walnut, has been reported to have a neuron protective effect, but the preventive effect on Alzheimer's disease (AD) related memory loss and the underlying mechanisms have not been well determined. Methods The senescence-accelerated mouse (SAM) is a useful model of AD-related memory impairment. In the present study, SAMP8 mice aged 4 months were chronically treated with ginsenoside (3 dose groups were given WOPs in diet for 6 months). The three groups were treated with WOPs 110, 220 and 440 mg/kg · bw per day, respectively. Placebo-treated aged mice and young ones (4 months old) were used as controls. In addition, SAMR1 mice were used as “normal aging” control. Results The beneficial role of WOPs was manifested in the prevention of memory loss in aged SAMP8 mice. The optimal dose of WOPs is 220 or 440 mg/kg per day. WOPs as found to significantly improve the memory ability of AD rats and anti-oxidase level significantly increased in serum. WOPs also reduced the content of Aβ and p-tau and improved the expression of PI3K and p-Akt/Akt in the hippocampus. Conclusions In conclusion, WOPs could improve the memory ability and reduce the content of Aβ and p-tau in SAMP8. The beneficial effects of WOPs were in part mediated by PI3K/Akt signaling pathway activation. Funding Sources This research was funded by the Bioactive Peptide Innovation Platform in Jilin province.

scholarly journals THE ROLE OF S100B IN AEROBIC TRAINING EFFICACY IN OLDER ADULTS WITH MILD VASCULAR COGNITIVE IMPAIRMENT

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S171-S172
Author(s):  
Rachel A Crockett ◽  
Cindy Barha ◽  
Ging-Yuek Robin Hsiung ◽  
Teresa Liu-Ambrose
Keyword(s):  
Older Adults ◽  
Cognitive Impairment ◽  
Cognitive Function ◽  
Calcium Binding ◽  
Aerobic Training ◽  
Exercise Intervention ◽  
Vascular Cognitive Impairment ◽  
Moderate Intensity ◽  
Beneficial Effects ◽  
Global Cognitive Function

Abstract Aerobic training improves cognitive and brain outcomes across different populations and neurocognitive disorders of aging, including mild subcortical ischemic vascular cognitive impairment (SIVCI). However, little is known of the underlying mechanisms through which aerobic training exerts its beneficial effects on the brain. Recently, S100 calcium-binding protein B (S100B) has been proposed as a possible mediator of aerobic training. At low levels, S100B is neurotrophic but at higher levels it is neurotoxic. Elevated levels of S100B have been associated with decreased performance on measures of global cognitive function. Thus, we conducted a secondary analysis of data collected from the proof-of-concept single-blind randomized controlled trial (NCT01027858) in older adults with mild SIVCI to determine whether the beneficial effects of 6-months, thrice weekly, moderate intensity aerobic training on cognitive performance is related to changes in S100B levels. In a subsample of 45 participants, blood samples were collected both before and after trial completion. Global cognitive function was assessed using Mini Mental State Examination (MMSE). At trial completion, aerobic training decreased circulating levels of S100B compared with usual care plus education (F(1,41) = 6.673, p = 0.013, ηp2 = 0.140; Figure 1). Furthermore, reduced S100B levels were associated with improved global cognitive function in those who received the aerobic exercise intervention (partial r = -0.519, p = 0.023). Together these findings suggest that S100B is a promising target mediating the beneficial effects of moderate-intensity aerobic training on brain health in older adults with mild SIVCI.

scholarly journals Sarcopenia and Cognitive Function: Role of Myokines in Muscle Brain Cross-Talk

Life ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 173
Author(s):  
Lucia Scisciola ◽  
Rosaria Anna Fontanella ◽  
Surina ◽  
Vittoria Cataldo ◽  
Giuseppe Paolisso ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Function ◽  
Cross Talk ◽  
Functional Decline ◽  
Geriatric Syndrome ◽  
Beneficial Effects ◽  
Brain Functions ◽  
And Function ◽  
Injury Protection

Sarcopenia is a geriatric syndrome characterized by the progressive degeneration of muscle mass and function, and it is associated with severe complications, which are falls, functional decline, frailty, and mortality. Sarcopenia is associated with cognitive impairment, defined as a decline in one or more cognitive domains as language, memory, reasoning, social cognition, planning, making decisions, and solving problems. Although the exact mechanism relating to sarcopenia and cognitive function has not yet been defined, several studies have shown that skeletal muscle produces and secrete molecules, called myokines, that regulate brain functions, including mood, learning, locomotor activity, and neuronal injury protection, showing the existence of muscle-brain cross-talk. Moreover, studies conducted on physical exercise supported the existence of muscle-brain cross-talk, showing how physical activity, changing myokines' circulating levels, exerts beneficial effects on the brain. The review mainly focuses on describing the role of myokines on brain function and their involvement in cognitive impairment in sarcopenia.

Evaluation of Cognitive Function in Migraine Patients

2013 ◽  
pp. 303-310
Author(s):  
Yuka Watanabe ◽  
Hideaki Tanaka ◽  
Koichi Hirata
Keyword(s):  
Cognitive Function ◽  
Event Related Potentials ◽  
Executive Dysfunction ◽  
Medicine Use ◽  
Electromagnetic Tomography ◽  
Pathogenic Factors ◽  
Related Potentials ◽  
Cortical Electrical Activity ◽  
Spatiotemporal Analyses ◽  
Underlying Mechanisms

Cognitive impairments are observed in a portion of patients with migraines, but the underlying mechanisms for this impairment are not known. Event-related potentials (ERPs) have been recorded to clarify the mechanism, and the ERPs suggest that migraineurs exhibit exacerbated attention, executive dysfunction, and lack of habituation. Many factors, such as migraine phase, subtype, illness severity and duration, and preventive medicine use, are directly and indirectly involved in the cognitive function of migraine patients. Few reports have systematically considered these factors during the evaluation of cognitive function in migraine patients. In addition, the neuroanatomical basis for these cognitive dysfunctions is not clear. Recently, spatiotemporal analyses of ERPs using multichannel EEG recording have been developed, which might aid in the clarification of the relationships between cognitive dysfunction and the underlying neuropathological mechanisms. The relationships between the cortical electrical activity distribution of ERP components using standardized low-resolution brain electromagnetic tomography (sLORETA) and pathogenic factors were clarified in this study.

scholarly journals Electroacupuncture Improves Cognitive Function in Senescence-Accelerated P8 (SAMP8) Mice via the NLRP3/Caspase-1 Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Zhitao Hou ◽  
Ruijin Qiu ◽  
Qingshuang Wei ◽  
Yitian Liu ◽  
Meng Wang ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Signaling Pathway ◽  
Tau Proteins ◽  
Morris Water Maze Test ◽  
Control Group ◽  
Caspase 1 ◽  
Cell Counts ◽  
Tnf Α ◽  
Hippocampal Morphology ◽  
Samp8 Mice

Background. Clinically, electroacupuncture (EA) is the most common therapy for aging-related cognitive impairment (CI). However, the underlying pathomechanism remains unidentified. The aims of this study were to observe the effect of EA on cognitive function and explore the potential mechanism by which EA acts on the NLRP3/caspase-1 signaling pathway. Main Methods. Thirty male SAMP8 mice were randomly divided into the model, the 2 Hz EA and 10 Hz EA groups. Ten male SAMR1 mice were assigned to the control group. Cognitive function was assessed through the Morris water maze test. Hippocampal morphology and cell death were observed by HE and TUNEL staining, respectively. The serum IL-1β, IL-6, IL-18, and TNF-α levels were measured by ELISA. Hippocampal NLRP3, ASC, caspase-1, GSDM-D, IL-1β, IL-18, Aβ, and tau proteins were detected by Western blotting. Key Findings. Cognitive function, hippocampal morphology, and TUNEL-positive cell counts were improved by both EA frequencies. The serum IL-1β, IL-6, IL-18, and TNF-α levels were decreased by EA treatment. However, 10 Hz EA reduced the number of TUNEL-positive cells in the CA1 region and serum IL-1β and IL-6 levels more effectively than 2 Hz EA. NLRP3/caspase-1 pathway-related proteins were significantly downregulated by EA, but 2 Hz EA did not effectively reduce ASC protein expression. Interestingly, both EA frequencies failed to reduce the expression of Aβ and tau proteins. Significance. The effects of 10 Hz EA at the GV20 and ST36 acupoints on the NLRP3/caspase-1 signaling pathway may be a mechanism by which this treatment relieves aging-related CI in mice.

scholarly journals Prodromal Intestinal Events in Alzheimer’s Disease (AD): Colonic Dysmotility and Inflammation Are Associated with Enteric AD-Related Protein Deposition

2020 ◽  
Vol 21 (10) ◽  
pp. 3523
Author(s):  
Carolina Pellegrini ◽  
Simona Daniele ◽  
Luca Antonioli ◽  
Laura Benvenuti ◽  
Vanessa D’Antongiovanni ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Cognitive Impairment ◽  
Mitochondrial Function ◽  
Citrate Synthase ◽  
Brain Pathology ◽  
Faecal Output ◽  
Caspase 1 ◽  
Related Proteins ◽  
Samp8 Mice

Increasing evidence suggests that intestinal dysfunctions may represent early events in Alzheimer’s disease and contribute to brain pathology. This study examined the relationship between onset of cognitive impairment and colonic dysfunctions in a spontaneous AD model before the full development of brain pathology. SAMP8 mice underwent Morris water maze and assessment of faecal output at four, six and eight months of age. In vitro colonic motility was examined. Faecal and colonic Aβ, tau proteins, α-synuclein and IL-1β were assessed by ELISA. Colonic citrate synthase activity was assessed by spectrophotometry. Colonic NLRP3, caspase-1 and ASC expression were evaluated by Western blotting. Colonic eosinophil density and claudin-1 expression were evaluated by immunohistochemistry. The effect of Aβ on NLRP3 signalling and mitochondrial function was tested in cultured cells. Cognitive impairment and decreased faecal output occurred in SAMP8 mice from six months. When compared with SAMR1, SAMP8 animals displayed: (1) impaired in vitro colonic contractions; (2) increased enteric AD-related proteins, IL-1β, active-caspase-1 expression and eosinophil density; and (3) decreased citrate synthase activity and claudin-1 expression. In THP-1 cells, Aβ promoted IL-1β release, which was abrogated upon incubation with caspase-1 inhibitor or in ASC-/- cells. Aβ decreased mitochondrial function in THP-1 cells. In SAMP8, enteric AD-related proteins deposition, inflammation and impaired colonic excitatory neurotransmission, occurring before the full brain pathology development, could contribute to bowel dysmotility and represent prodromal events in AD.

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