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Quorum sensing peptides (QSPs) are bacterial peptides produced by Gram-positive bacteria to communicate with their peers in a cell-density dependent manner. These peptides do not only act as interbacterial communication signals, but can also have effects on the host. Compelling evidence demonstrates the presence of a gut-brain axis and more specifically, the role of the gut microbiota in microglial functioning. The aim of this study is to investigate microglial activating properties of a selected QSP (PapRIV) which is produced by Bacillus cereus species. PapRIV showed in vitro activating properties of BV-2 microglia cells and was able to cross the in vitro Caco-2 cell model and reach the brain. In vivo peptide presence was also demonstrated in mouse plasma. The peptide caused induction of IL-6, TNFα and ROS expression and increased the fraction of ameboid BV-2 microglia cells in an NF-κB dependent manner. Different metabolites were identified in serum, of which the main metabolite still remained active. PapRIV is thus able to cross the gastro-intestinal tract and the blood–brain barrier and shows in vitro activating properties in BV-2 microglia cells, hereby indicating a potential role of this quorum sensing peptide in gut-brain interaction. [ABSTRACT FROM AUTHOR]

Background In humans, in utero exposure to ionising radiation results in an increased prevalence of neurological aberrations, such as small head size, mental retardation and decreased IQ levels. Yet, the association between early damaging events and long-term neuronal anomalies remains largely elusive. Methods Mice were exposed to different X-ray doses, ranging between 0.0 and 1.0 Gy, at embryonic days (E) 10, 11 or 12 and subjected to behavioural tests at 12 weeks of age. Underlying mechanisms of irradiation at E11 were further unravelled using magnetic resonance imaging (MRI) and spectroscopy, diffusion tensor imaging, gene expression profiling, histology and immunohistochemistry. Results Irradiation at the onset of neurogenesis elicited behavioural changes in young adult mice, dependent on the timing of exposure. As locomotor behaviour and hippocampal-dependent spatial learning and memory were most particularly affected after irradiation at E11 with 1.0 Gy, this condition was used for further mechanistic analyses, focusing on the cerebral cortex and hippocampus. A classical p53-mediated apoptotic response was found shortly after exposure. Strikingly, in the neocortex, the majority of apoptotic and microglial cells were residing in the outer layer at 24 h after irradiation, suggesting cell death occurrence in differentiating neurons rather than proliferating cells. Furthermore, total brain volume, cortical thickness and ventricle size were decreased in the irradiated embryos. At 40 weeks of age, MRI showed that the ventricles were enlarged whereas N-acetyl aspartate concentrations and functional anisotropy were reduced in the cortex of the irradiated animals, indicating a decrease in neuronal cell number and persistent neuroinflammation. Finally, in the hippocampus, we revealed a reduction in general neurogenic proliferation and in the amount of Sox2-positive precursors after radiation exposure, although only at a juvenile age. Conclusions Our findings provide evidence for a radiation-induced disruption of mouse brain development, resulting in behavioural differences. We propose that alterations in cortical morphology and juvenile hippocampal neurogenesis might both contribute to the observed aberrant behaviour. Furthermore, our results challenge the generally assumed view of a higher radiosensitivity in dividing cells. Overall, this study offers new insights into irradiation-dependent effects in the embryonic brain, of relevance for the neurodevelopmental and radiobiological field. [ABSTRACT FROM AUTHOR]

Objective: Alzheimer's disease (AD) is characterized by noticeable neuropsychiatric symptoms and cognitive decline [1]. In addition, cardiovascular disease (CVD) is a known etiological hallmark of AD pathogenesis [2]. Recent epidemiological evidence suggests an interplay between arterial stiffness (AS) and AD [3]. Therefore, we aimed for an in-depth vascular characterization of the APP23+/− overexpressing AD mouse model (APP23+/−). Methods: Blood pressure (BP, CODA) and aortic pulse wave velocity (aPWV, VEVO2100) were measured in vivo, whereas isometric vascular reactivity (organ chambers), isobaric AS (Peterson modulus (Ep)) and compliance (Rodent Oscillatory Tension Set-up for Arterial Compliance) were determined ex vivo in thoracic aorta segments of APP23+/− mice (male, n = 10) vs. C57BL/6 mice (male, n = 18) at the age of 6 months. Corticosterone levels were analysed on blood serum by means of ELISA. The data are given as mean ± SEM. Results: APP23+/− mice showed elevated corticosterone levels (Figure 1A) associated with increased peripheral systolic BP (Figure 1B) and aPWV in vivo (Figure 1C), and decreased isometric adrenoreceptor-dependent contractions ex vivo upon phenylephrine stimulation (Figure 1D). Ex vivo isobaric AS measurements at baseline disclosed a smaller aortic diameter of APP23+/− mice (Figure 2A) resulting in reduced compliance (Figure 2B), with no Ep differences (Figure 2C). Upon phenylephrine treatment, a smaller effect on aortic constriction (Figure 2D), compliance (Figure 2E) and Ep (Figure 2F) was observed for APP23+/− animals, corresponding to reduced isometric contractions (Figure 1D). Conclusion: APP23+/− mice have increased corticosterone levels leading to increased BP, aPWV and reduced isometric contractility, resulting in decreased isobaric compliance, but with unchanged arterial wall biomechanics. [ABSTRACT FROM AUTHOR]

The interest for acetylcholinesterase inhibitors in the treatment of Alzheimer’s disease has been greatly renewed owing to the discovery of a broad range of additional cholinergic and non-cholinergic effects, exploitable to maximize the efficacy of these drugs beyond merely improving intellectual functions at the symptomatic level. The age-dependent cognitive decline in the valid APP23 transgenic mouse model for Alzheimer’s disease was employed to evaluate disease-modifying efficacy of chronic treatment with donepezil. At age 6 weeks, heterozygous APP23 mice and control littermates were subcutaneously implanted with osmotic pumps delivering saline or donepezil (0.27 or 0.58 mg/kg per day). After 2 months of treatment, a 3-week wash-out period was allowed to prevent bias from sustained symptomatic effects before cognitive evaluation in the Morris water maze commenced. Donepezil (0.27 mg/kg per day)-treated APP23 mice performed significantly better than their sham-treated counterparts during the Morris water maze acquisition phase and the subsequent probe or retention trial. Chronic donepezil (0.27 mg/kg per day) treatment improved spatial accuracy in APP23 mice as to reach the same level of performance as wild-type control animals on this complex visual–spatial learning task. This is the first study reporting disease-modifying efficacy of donepezil at the level of cognitive performance in transgenic mice modeling Alzheimer’s disease. [ABSTRACT FROM AUTHOR]

Recent advances in the understanding of the pathophysiological mechanisms underlying Alzheimer's disease have pointed to novel strategies for drug development. Animal models have contributed considerably to these advances, and will have a key role in the evaluation of therapeutics that could have the potential not just to alleviate the dementia associated with Alzheimer's disease, but to modify the disease process. Here, we summarize and critically evaluate current rodent models of dementia, and discuss their role in drug discovery and development. [ABSTRACT FROM AUTHOR]

Presents a study which discussed the symptomatic effect of donepezil, rivastigmine, galantamine and memantine on cognitive deficits in the APP23 model. Definition of Alzheimer's disease; Effect of the treatment in the wild-type animals; Results of the study.