High Salt Elicits Brain Inflammation and Cognitive Dysfunction, Accompanied by Alternations in the Gut Microbiota and Decreased SCFA Production

2020 ◽  
Vol 77 (2) ◽  
pp. 629-640
Author(s):  
Li Hu ◽  
Shaoping Zhu ◽  
Xiaoping Peng ◽  
Kanglan Li ◽  
Wanjuan Peng ◽  
...  

Background: Excessive salt intake is considered as an important risk factor for cognitive impairment, which might be the consequence of imbalanced intestinal homeostasis. Objective: To investigate the effects of dietary salt on the gut microbiota and cognitive performance and the underlying mechanisms. Methods: Adult female C57BL/6 mice were maintained on either normal chow (control group, CON) or sodium-rich chow containing 8% NaCl (high-salt diet, HSD) for 8 weeks. Spatial learning and memory ability, short-chain fatty acids (SCFAs) concentrations, gut bacterial flora composition, blood-brain barrier permeability, and proinflammatory cytokine levels and apoptosis in the brain were evaluated. Results: The mice fed a HSD for 8 weeks displayed impaired learning and memory abilities. HSD significantly reduced the proportions of Bacteroidetes (S24-7 and Alloprevotella) and Proteobacteria and increased that of Firmicutes (Lachnospiraceae and Ruminococcaceae). SCFA concentrations decreased in the absolute concentrations of acetate, propionate, and butyrate in the fecal samples from the HSD-fed mice. The HSD induced both BBB dysfunction and microglial activation in the mouse brain, and increased the IL-1β, IL-6, and TNF-α expression levels in the cortex. More importantly, the degree of apoptosis was higher in the cortex and hippocampus region of mice fed the HSD, and this effect was accompanied by significantly higher expression of cleaved caspase-3, caspase-3, and caspase-1. Conclusion: The HSD directly causes cognitive dysfunction in mice by eliciting an inflammatory environment and triggering apoptosis in the brain, and these effects are accompanied by gut dysbiosis, particularly reduced SCFA production.

Author(s):  
Asma Ulhusna Shaimi ◽  
Hasmah Abdullah ◽  
Zalina Ismail ◽  
Wan Amir Nizam Wan Ahmad

Dehydroepiandrosterone sulphate (DHEAS) is a neurosteroid that is found in greater concentration within the brain rather than in any other body organ (Corpechot et al., 1981) and studies have shown that in the brain, DHEAS has a role in enhancing both learning and memory (Markowski et.al., 2001). This present study investigated the relationship between DHEAS and spatial learning and memory in the rat hippocampus. Male Sprague-Dawley rats were divided into two groups and their spatial learning behaviour was evaluated with the Morris Water Maze. The intensity of DHEAS was simultaneously recorded in real time via the Fiber Fluorescence Microscopy (FFM) S-650 probe of the Cellvisio system. There were significant changes in the swimming pattern of the experimental groups obtained via the Morris Water Maze from day 1 until day 5 and day 6 for the probe test. Meanwhile, it was also seen that the intensity of DHEAS fluorescence increased in parallel to the swimming pattern of the experimental rats in comparison to the control group. The findings suggest that the changes in DHEAS fluorescence has a strong link to both spatial learning and memory.


2020 ◽  
Vol 23 (5) ◽  
pp. 402-410 ◽  
Author(s):  
Lin-Zi Li ◽  
Shan-Shan Lei ◽  
Bo Li ◽  
Fu-Chen Zhou ◽  
Ye-Hui Chen ◽  
...  

Aim and Objective: The Dendrobium officinalis flower (DOF) is popular in China due to common belief in its anti-aging properties and positive effects on “nourish yin”. However, there have been relatively few confirmatory pharmacological experiments conducted to date. The aim of this work was to evaluate whether DOF has beneficial effects on learning and memory in senescent rats, and, if so, to determine its potential mechanism of effect. Materials and Methods: SD rats were administrated orally DOF at a dose of 1.38, or 0.46 g/kg once a day for 8 weeks. Two other groups included a healthy untreated control group and a senescent control group. During the 7th week, a Morris water maze test was performed to assess learning and memory. At the end of the experiment, serum and brain samples were collected to measure concentrations of antioxidant enzymes, including malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GSH-Px) in serum, and the neurotransmitters, including γ-aminobutyric acid (γ-GABA), Glutamic (Glu), and monoamine oxidase B (MAO-B) in the brain. Histopathology of the hippocampus was assessed using hematoxylin-eosin (H&E) staining. Results: The results suggested that treatment with DOF improved learning as measured by escape latency, total distance, and target quadrant time, and also increased levels of γ-GABA in the brain. In addition, DOF decreased the levels of MDA, Glu, and MAO-B, and improved SOD and GSHPx. Histopathological analysis showed that DOF also significantly reduced structural lesions and neurodegeneration in the hippocampus relative to untreated senescent rats. Conclusion: DOF alleviated brain aging and improved the spatial learning abilities in senescent rats, potentially by attenuating oxidative stress and thus reducing hippocampal damage and balancing the release of neurotransmitters.


2010 ◽  
Vol 104 (9) ◽  
pp. 1297-1303 ◽  
Author(s):  
Yan-Hong Huang ◽  
Qing-Hong Zhang

The present study was undertaken to investigate the antioxidant effect of chronic ingestion of genistein (Gen) against neural death in the brain of ovariectomised (Ovx) rats. The rats were randomly divided into five groups, i.e. sham-operated (sham), Ovx-only, Ovx with 17β-oestradiol, Ovx with low (15 mg/kg) and high (30 mg/kg) doses of Gen (Gen-L and Gen-H), and were orally administered daily with drugs or vehicle for 6 weeks. The learning and memory abilities were measured by Morris water maze test. Oxidative damages in the brain were evaluated by the level of superoxide dismutase (SOD), malondialdehyde (MDA) and monoamine oxidase (MAO) activities. Neural apoptosis was shown by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) staining and caspase-3 activity. In the visual learning and memory test, there were no significant differences among the population means of the five groups. While in the probe trial test, the Gen-L group instead of the Gen-H group exhibited reduced escape latency and increased memory frequency than the Ovx group. Although both doses of Gen could reduce acetylcholinesterase activity, only a low dose of Gen could diminish MDA activity significantly in frontal cortex and enhance SOD content in the hippocampus. In contrast, MAO content was decreased in the cortex by either dose of Gen, while in the hippocampus, only a high dose of Gen appeared to be effective. Interestingly, Gen at both the doses could attenuate the increased number of TUNEL-positive neurons and caspase-3 activity in Ovx rats. These results suggest that Gen confers protection against Ovx-induced neurodegeneration by attenuating oxidative stress, lipid peroxidation and the mitochondria-mediated apoptotic pathway in a region- and dose-dependent manner.


2005 ◽  
Vol 25 (12) ◽  
pp. 1586-1595 ◽  
Author(s):  
Olof Bendel ◽  
Tjerk Bueters ◽  
Mia von Euler ◽  
Sven Ove Ögren ◽  
Johan Sandin ◽  
...  

The pyramidal neurons of the hippocampal CA1 region are essential for cognitive functions such as spatial learning and memory, and are selectively destroyed after cerebral ischemia. To analyze whether degenerated CA1 neurons are replaced by new neurons and whether such regeneration is associated with amelioration in learning and memory deficits, we have used a rat global ischemia model that provides an almost complete disappearance (to approximately 3% of control) of CA1 neurons associated with a robust impairment in spatial learning and memory at two weeks after ischemia. We found that transient cerebral ischemia can evoke a massive formation of new neurons in the CA1 region, reaching approximately 40% of the original number of neurons at 90 days after ischemia (DAI). Co-localization of the mature neuronal marker neuronal nuclei with 5-bromo-2'-deoxyuridine in CA1 confirmed that neurogenesis indeed had occurred after the ischemic insult. Furthermore, we found increased numbers of cells expressing the immature neuron marker polysialic acid neuronal cell adhesion molecule in the adjacent lateral periventricular region, suggesting that the newly formed neurons derive from this region. The reappearance of CA1 neurons was associated with a recovery of ischemia-induced impairments in spatial learning and memory at 90 DAI, suggesting that the newly formed CA1 neurons restore hippocampal CA1 function. In conclusion, these results show that the brain has an endogenous capacity to form new nerve cells after injury, which correlates with a restoration of cognitive functions of the brain.


Author(s):  
Narges Marefati ◽  
Amin Mokhtari-Zaer ◽  
Farimah Beheshti ◽  
Sareh Karimi ◽  
Zahra Mahdian ◽  
...  

Abstract Background Modulatory effects of soy extract and estradiol on the central nervous system (CNS) have been reported. The effect of soy on scopolamine-induced spatial learning and memory in comparison to the effect of estradiol was investigated. Materials and methods Ovariectomized rats were divided into the following groups: (1) control, (2) scopolamine (Sco), (3) scopolamine-soy 20 (Sco-S 20), (4) scopolamine-soy 60 (Sco-S 60), (5) scopolamine-estradiol 20 (Sco-E 20) and (6) scopolamine-estradiol 60 (Sco-E 60). Soy extract, estradiol and vehicle were administered daily for 6 weeks before training in the Morris water maze (MWM) test. Scopolamine (2 mg/kg) was injected 30 min before training in the MWM test. Results In the MWM, the escape latency and traveled path to find the platform in the Sco group was prolonged compared to the control group (p < 0.001). Treatment by higher doses of soy improved performances of the rats in the MWM (p < 0.05 – p < 0.001). However, treatment with both doses of estradiol (20 and 60 μg/kg) resulted in a statistically significant improvement in the MWM (p < 0.01 – p < 0.001). Cortical, hippocampal and serum levels of malondialdehyde (MDA), as an index of lipid peroxidation, were increased which was prevented by soy extract and estradiol (p < 0.001). Cortical, hippocampal as well as serum levels of the total thiol, superoxide dismutase (SOD) and catalase (CAT) in Sco group were lower than the control group (p < 0.001) while they were enhanced when the animals were treated by soy extract and estradiol (p < 0.01 – p < 0.001). Conclusions It was observed that both soy extract and estradiol prevented learning and memory impairments induced by scopolamine in ovariectomized rats. These effects can be attributed to their protective effects on oxidative damage of the brain tissue.


2010 ◽  
Vol 17 (2) ◽  
pp. 119-127 ◽  
Author(s):  
Yutaka Oomura ◽  
Shuji Aou ◽  
Kouji Fukunaga

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Ning Ding ◽  
Jing Jiang ◽  
Menghan Lu ◽  
Jiatong Hu ◽  
Yiyuan Xu ◽  
...  

Objective. To investigate the effect of manual acupuncture (MA) on NLRP3 inflammasome-related proteins. Methods. SAMP8 mice were randomly divided into Alzheimer’s disease (AD) group, the MA group, and the medicine (M) group. Mice in the M group were treated with donepezil hydrochloride at 0.65 μg/g. In the MA group, MA was applied on Baihui (GV20) and Yintang (GV29) for 20 min and then pricked at Shuigou (GV26). The Morris water maze was applied to assess spatial learning and memory. Immunohistochemical staining and western blot analysis were used to observe the expression of NLRP3 inflammasome-related proteins. Results. Compared with the normal (N) control group, spatial learning and the memory capabilities of the AD group significantly decreased (p<0.01). The number of NLRP3, ASC, Caspase-1, and IL-1β positively stained cells in the AD group was higher than the N group, and the relative expression levels of the above proteins were significantly higher than those in the N group (p<0.01). These changes were reversed by both MA and donepezil (p<0.01). Conclusion. MA can improve the learning and memory capabilities of SAMP8 mice. The negative regulation of the NLRP3/Caspase-1 pathway in the hippocampus may be a possible mechanism of MA in the treatment of AD.


2021 ◽  
Author(s):  
Majid Eslami ◽  
Laleh Khorshidi ◽  
Maryam Ghasemi ◽  
Amir Rashidian ◽  
Mahdi Mirghazanfari ◽  
...  

Abstract 3,4‐methylenedioxymethamphetamine (MDMA) or "Ecstasy", which has been used for recreational purposes, is shown to cause learning and memory impairment. Statins, beyond their efficient cholesterol-lowering action through inhibition of 3-hydroxy-3-methylglutaryl-CoA (HMG-COA) reductase, possess multiple neuroprotective impacts referred to as pleiotropic effects. In this regard, we aimed to investigate the protective effect of atorvastatin and rosuvastatin in MDMA-induced neurotoxicity. Adult male Wistar rats received atorvastatin (5, 10, 20 mg/kg; orally) and rosuvastatin (5, 10, 20 mg/kg; orally) for 21 consecutive days. Then, Morris water maze (MWM) was performed to examine learning and memory functions. Rats were injected with MDMA (2.5, 5, and 10 mg/kg; I.P) 30 min before training sessions in 4 training days of MWM task. Afterward, rats were sacrificed under general anesthesia and their hippocampuses were dissected to evaluate reactive oxygen species (ROS) production, lipid peroxidation (LPO), and caspase-3 and -9 activities. Our Findings showed that MDMA impaired spatial memory functions and dramatically upregulated ROS production, LPO, and caspase-3 and 9 activities. Also, atorvastatin (5, 10, 20 mg/kg) and rosuvastatin (20 mg/kg) significantly improved memory performances and inhibited upregulation of ROS, LPO, and caspase-3 and -9 activities induced by MDMA. In conclusion, the amelioration of MDMA-induced memory impairment and hippocampal apoptosis through atorvastatin and rosuvastatin could be accredited to the observed suppression of ROS production, LPO, and caspase-3 and -9 activities, since excessive exposure of hippocampus to oxidative stress enhanced apoptotic caspases activities, promoted to neuronal apoptosis.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Dongsheng Dai ◽  
Biqiong Zheng ◽  
Zenggui Yu ◽  
Shizhu Lin ◽  
Yijie Tang ◽  
...  

Abstract Background Sleep deprivation (SD) often leads to complex detrimental consequences, though the mechanisms underlying these dysfunctional effects remain largely unknown. We investigated whether the right stellate ganglion block in rats can improve the spatial learning and memory dysfunction induced by sleep deprivation by alleviating the damage of hippocampus in rats. Methods Sixty four male Sprague Dawley rats were randomly divided into four groups: Control, SD (sleep deprivation), SGB (stellate ganglion block) and SGB + SD (stellate ganglion block+ sleep deprivation) (n = 16). The SGB and SD + SGB groups were subjected to right stellate ganglion block through posterior approach method once per day. SD and SD + SGB groups were treated with modified multi-platform water environment method for 96 h sleep deprivation in rats and their body weights were analyzed. Histopathological changes of hippocampal neurons in rats and the expression of Caspase-3 in hippocampus of rats was detected by western blotting. ELISA was used to detect the content of IL-6, IL-1 in hippocampus and serum melatonin levels. Results Compared with the group SD, the spatial learning and memory function of the group SD + SGB was improved, the weight loss was alleviated, the pathological damage of the hippocampus was reduced and the expression of IL-6, IL-1β and Caspase-3 in the hippocampus was decreased. The content of rat serum melatonin was also increased. Conclusions The right stellate ganglion block can improve the spatial learning and memory dysfunction of rats with sleep deprivation, and the underlying mechanism may be related to alleviating the apoptosis and inflammation of hippocampus of rats with sleep deprivation.


2020 ◽  
Vol 107 (1) ◽  
pp. 30-39 ◽  
Author(s):  
S. Raman ◽  
M. Asle-Rousta ◽  
M. Rahnema

AbstractSocial isolation damages the nervous system by weakening the antioxidant system and leading to behavioral disorders. Fennel (Foeniculum vulgare Mill.) is an herbal plant that has antioxidant and neuroprotective properties. The objective of this study was to evaluate the effect of fennel methanol extract and its major component trans-anethole on spatial learning and memory, anxiety and depression in male rats exposed to social isolation stress.Rats were divided into six groups of Control (C), Fennel (F), trans-Anethole (A), Isolation, Isolation-F and Isolation-A. The rats were kept in the cage alone for 30 days to induce isolation. Fennel extract (150 mg/kg) and trans-anethole (80 mg/kg) were also gavaged during this period. At the end of the course, spatial learning and memory, anxiety and depression were measured by Morris water maze (MWM), elevated plus maze (EPM) and forced swimming test (FST), respectively.Learning and memory were impaired in isolated rats. Swimming time and distance to reach the hidden platform in these animals increased compared with controls (P < 0.05). In the EPM test, the percentage of open arm entries and open arm time also decreased significantly in the Isolation group (P < 0.01). The immobilization time in FST also increased significantly in these animals compared with the Control group (P < 0.001). Fennel and trans-anethole were both able to eliminate these changes in isolated rats.It is concluded that fennel and its major component, trans-anethole are suitable candidates for the prevention and treatment of stress-induced neurological disorders.


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