Long-term combined administration of Bifidobacterium bifidum TMC3115 and Lactobacillus plantarum 45 alleviates spatial memory impairment and gut dysbiosis in APP/PS1 mice

2020 ◽  
Vol 367 (7) ◽  
Author(s):  
Feng Wang ◽  
Tong Xu ◽  
Yujie Zhang ◽  
Tingting Zheng ◽  
Yunling He ◽  
...  

ABSTRACT This study aimed to determine the effects of Bifidobacterium bifidum TMC3115, Lactobacillus plantarum 45 (LP45) and their combined use on cognitive performance and gut microbiota in APP/PS1 mice. The APP/PS1 mice were randomly divided into four groups: Alzheimer's disease (AD) model group, TMC3115 group [1 × 109 colony forming unit (CFU)], LP45 group (1 × 109 CFU) and a mixture group of TMC3115 (5 × 108 CFU) and LP45 (5 × 108 CFU). The wild-type littermates were chosen as normal control. The mice were sacrificed at the end of 22 weeks after behavioral evaluation. Collected cecum content was analyzed using 16S rRNA sequencing. Combined use of TMC3115 and LP45 significantly increased the times across the platform, time spent in the target quadrant compared with the AD, TMC3115 and LP45 groups in Morris water maze test. Microbiota analysis showed that combined TMC3115 and LP45 supplementation significantly increased observed species and beta diversity, and reversed gut dysbiosis by decreasing the abundance of Bacteroides and increasing the abundance of Acetatifactor and Millionella. These results indicate the long-term combined administration of TMC3115 and LP45 can improve spatial memory impairment in APP/PS1 mice and suggest that modifying the gut microbiome may provide potential benefits for AD patients.

2020 ◽  
Vol 45 (5) ◽  
pp. 877-886 ◽  
Author(s):  
Adán de Salas-Quiroga ◽  
Daniel García-Rincón ◽  
Daniel Gómez-Domínguez ◽  
Manuel Valero ◽  
Samuel Simón-Sánchez ◽  
...  

2013 ◽  
Vol 26 (2) ◽  
pp. 112-119 ◽  
Author(s):  
Kinga Burda-Malarz ◽  
Krzysztof Kus ◽  
Piotr Ratajczak ◽  
Anna Czubak ◽  
Elżbieta Nowakowska ◽  
...  

Introduction and aimsDependence on ethanol increases the risk of depression in patients and leads to a damage and deficiencies of brain function, which manifest in cognitive functions impairment. Aripiprazole (ARI) is an atypical antipsychotic drug, which has also been shown to have a beneficial effect on cognitive function. Results of many studies show that, for ARI's antidepressant effect to manifest itself, it is necessary to use a combined therapy with a drug from the group of selective serotonin reuptake inhibitors (SSRIs). The aim of this paper was to assess the antidepressant and impact of ARI on spatial memory in alcohol-preferring rats (EtNPRs).Design and methodsIn our study, we used Porsolt's forced swimming test (antidepressant effect) and Morris water maze test. The tests have been conducted upon administration of ARI (6 mg/kg i.p.), fluoxetine (FLX; 5 mg/kg p.o.) and combined administration of both drugs in alcohol-dependent rats.ResultsThe results of behavioural tests carried out have shown a lack of antidepressant and procognitive effects of either ARI or FLX in EtPRs after acute and chronic treatment. Combined administration of both drugs would lead to spatial memory deterioration in the study animals.Discussion and conclusionsOur results suggest that ARI applied in the experiment had no antidepressant effect and failed to improve spatial memory in study rats. Potential antidepressant and procognitive properties of this drug resulting from its mechanism of action encourage attempts (design) of further research aimed at developing a dose, which will show such effects in alcohol-preferring animals.


2018 ◽  
Vol 215 (10) ◽  
pp. 2554-2566 ◽  
Author(s):  
Jacquelyn Nestor ◽  
Yoshiyuki Arinuma ◽  
Tomás S. Huerta ◽  
Czeslawa Kowal ◽  
Elham Nasiri ◽  
...  

Cognitive impairment occurs in 40–90% of patients with systemic lupus erythematosus (SLE), which is characterized by autoantibodies to nuclear antigens, especially DNA. We discovered that a subset of anti-DNA antibodies, termed DNRAbs, cross reacts with the N-methyl-d-aspartate receptor (NMDAR) and enhances NMDAR signaling. In patients, DNRAb presence associates with spatial memory impairment. In a mouse model, DNRAb-mediated brain pathology proceeds through an acute phase of excitotoxic neuron loss, followed by persistent alteration in neuronal integrity and spatial memory impairment. The latter pathology becomes evident only after DNRAbs are no longer detectable in the brain. Here we investigate the mechanism of long-term neuronal dysfunction mediated by transient exposure to antibody. We show that activated microglia and C1q are critical mediators of neuronal damage. We further show that centrally acting inhibitors of angiotensin-converting enzyme (ACE) can prevent microglial activation and preserve neuronal function and cognitive performance. Thus, ACE inhibition represents a strong candidate for clinical trials aimed at mitigating cognitive dysfunction.


2019 ◽  
Vol 244 (12) ◽  
pp. 1017-1027 ◽  
Author(s):  
Guojiao Wu ◽  
Zhiheng Chen ◽  
Peipei Wang ◽  
Mingyi Zhao ◽  
Masayuki Fujino ◽  
...  

Hypoxic–ischemic brain damage (HIBD) is one of the leading causes of brain injury in infant with high risk of mortality and disability; therefore, it is important to explore more feasible and effective treatment strategies. Here, we assessed the neuroprotective effects of different hydrogen inhalation times for the treatment of HIBD. We induced hypoxia–ischemia in Sprague–Dawley rats (postnatal day 7, both sexes), followed by treatment with hydrogen inhalation for 30, 60, or 90 min. Morphological brain injury was assessed by Nissl and TUNEL staining. Acute inflammation was evaluated by examining the expression of interleukin-1β (IL-1β) and NF-κB p65, as well as Iba-1 immunofluorescence in the brain. Neural apoptosis was evaluated by examining the expression of P-JNK and p53 as well as NeuN immunofluorescence. Neurobehavioral function of rats was evaluated by Morris water maze test at 36 days after surgery. The results showed that hypoxia–ischemia injury induced the inflammatory response of microglia; however, these changes were inhibited by hydrogen inhalation. The inhibitory effects became more apparent as the treatment duration increased ( P < 0.05). Furthermore, hypoxia–ischemia induced neuronal damage and increased the expression of the apoptotic factors, P-JNK, and p53, which were attenuated by hydrogen inhalation ( P < 0.05). Hypoxia–ischemia caused long-term spatial memory deficits during brain maturation, which were ameliorated by hydrogen inhalation ( P < 0.01). In conclusion, hypoxia–ischemia induced severe long-term damage to the brain, which could be alleviated by hydrogen inhalation in a time-dependent manner. Impact statement Oxidative stress is known to be involved in the main pathological progression of neonatal hypoxic–ischemic brain damage (HIBD). Hydrogen (H2) is an antioxidant that can be used to treat HIBD; however, the mechanism by which hydrogen may be used as a promising treatment for neonates with HIBD is not very clear. This study demonstrated that inhaled H2 is neuroprotective against HIBD in SpragueDawley rats by inhibiting the brain’s inflammatory response and neuronal apoptosis or damage and protecting against spatial memory decline. Further, this study showed that inhaled H2 has potential as a therapeutic approach for HIBD. This is relevant to clinical treatment protocols when hypoxia–ischemia is suspected in neonates.


Hippocampus ◽  
2010 ◽  
Vol 22 (3) ◽  
pp. 399-408 ◽  
Author(s):  
Raül Andero ◽  
Núria Daviu ◽  
Rosa Maria Escorihuela ◽  
Roser Nadal ◽  
Antonio Armario

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
O M Peiro Ibanez ◽  
N Farre ◽  
J Ordonez-Llanos ◽  
A Garcia ◽  
G Bonet ◽  
...  

Abstract Introduction After an acute coronary syn bdrome (ACS) patients are at high risk of cardiovascular morbidity and mortality. In this scenario, Growth differentiation factor-15 (GDF-15) and Stromal cell derived factor-1 (SDF-1) has been reported as potential biomarkers in ACS. However, there is limited data about their combined use in long-term prognosis. Purpose To study the long-term prognostic value of GDF-15 and SDF-1 in ACS. Methods We included patients with ACS who underwent coronary angiography. During angiography an arterial blood sample was collected. Plasma SDF-1 and GDF-15 were measured and clinical data and long-term events were obtained. The cut-off point of SDF-1 and GDF-15 was identified individually by receiver operating characteristic curves. Patients were classified into 3 groups: 1) both biomarkers below cut-off points; 2) only one biomarker above cut-off points; 3) both biomarkers above cut-off points. Results A total of 238 patients were included. The median (IQR) age was 64 (55–74) year and 27.3% were female. Of all patients, 60.9% were admitted with non-ST-elevation myocardial infarction, 22.7% with ST-elevation myocardial infarction and 16.4% with unstable angina. The cut-off point of SDF-1 was 3283.5pg/mL and GDF-15 was 1849ng/L. A total of 127 patients were in group 1, 64 in group 2 and 47 in group 3. Group 3 patients were associated with older age, hypertension, dyslipidemia, diabetes mellitus and history of myocardial infarction (MI), stroke, chronic kidney disease and peripheral artery disease. Besides, they were more likely to have left ventricular dysfunction (ejection fraction <40%) and significant three vessels stenosis. During 6.5 years of follow-up 8 patients died (6.3%) in group 1, 7 patients died (10.9%) in group 2 and 25 patients died (53.2%) in group 3 (Figure 1). Multivariate Cox analysis showed that high levels of SDF-1 and GDF-15 (group 3) were an independent predictor of all-cause death (HR 5.8; 95% CI 2.4 - 14.1; p<0.001) and the composite of major adverse cardiovascular events (MACE) which were identified as all-cause death, nonfatal MI and heart failure (HR 3.9; 95% CI 2.1 - 7.3; p<0.001). During follow-up 1 patient had heart failure in group 1 (0.8%), 3 patients (4.7%) in group 2 and 9 patients (19.1%) in group 3. Despite the low number of events of heart failure, the multivariate competing risks regression showed association between group 3 and heart failure during follow-up (HR 28.0; 95% CI 3.5 - 225.2; p=0.002). Higher levels of SDF-1 and GDF-15 (group 3) were not associated with new MI in multivariate competing risks regression. Regarding group 2, all multivariate analyses were non-significant. Cumulative survival and incidence curves Conclusions Higher values of combined GDF-15 and SDF-1 are an excellent predictor of all-cause death, MACE and heart failure in long-term follow-up of patients with ACS. The combined use of SDF-1 and GDF-15 may be useful in long-term ACS prognosis.


2016 ◽  
Vol 53 ◽  
pp. 85-92 ◽  
Author(s):  
Caridad López-Granero ◽  
Ana M. Ruiz-Muñoz ◽  
Francisco A. Nieto-Escámez ◽  
María T. Colomina ◽  
Michael Aschner ◽  
...  

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