Adult hippocampal neurogenesis and its role in Alzheimer's disease

The hippocampus, a brain area critical for learning and memory, is especially vulnerable to damage at early stages of Alzheimer's disease (AD). Emerging evidence has indicated that altered neurogenesis in the adult hippocampus represents an early critical event in the course of AD. Although causal links have not been established, a variety of key molecules involved in AD pathogenesis have been shown to impact new neuron generation, either positively or negatively. From a functional point of view, hippocampal neurogenesis plays an important role in structural plasticity and network maintenance. Therefore, dysfunctional neurogenesis resulting from early subtle disease manifestations may in turn exacerbate neuronal vulnerability to AD and contribute to memory impairment, whereas enhanced neurogenesis may be a compensatory response and represent an endogenous brain repair mechanism. Here we review recent findings on alterations of neurogenesis associated with pathogenesis of AD, and we discuss the potential of neurogenesis-based diagnostics and therapeutic strategies for AD

Probing sporadic and familial Alzheimer's disease using induced pluripotent stem cells.

Our understanding of Alzheimer's disease pathogenesis is currently limited by difficulties in obtaining live neurons from patients and the inability to model the sporadic form of the disease. It may be possible to overcome these challenges by reprogramming primary cells from patients into induced pluripotent stem cells (iPSCs). Here we reprogrammed primary fibroblasts from two patients with familial Alzheimer's disease, both caused by a duplication of the amyloid-β precursor protein gene (APP; termed APP(Dp)), two with sporadic Alzheimer's disease (termed sAD1, sAD2) and two non-demented control individuals into iPSC lines. Neurons from differentiated cultures were purified with fluorescence-activated cell sorting and characterized. Purified cultures contained more than 90% neurons, clustered with fetal brain messenger RNA samples by microarray criteria, and could form functional synaptic contacts. Virtually all cells exhibited normal electrophysiological activity. Relative to controls, iPSC-derived, purified neurons from the two APP(Dp) patients and patient sAD2 exhibited significantly higher levels of the pathological markers amyloid-β(1-40), phospho-tau(Thr 231) and active glycogen synthase kinase-3β (aGSK-3β). Neurons from APP(Dp) and sAD2 patients also accumulated large RAB5-positive early endosomes compared to controls. Treatment of purified neurons with β-secretase inhibitors, but not γ-secretase inhibitors, caused significant reductions in phospho-Tau(Thr 231) and aGSK-3β levels. These results suggest a direct relationship between APP proteolytic processing, but not amyloid-β, in GSK-3β activation and tau phosphorylation in human neurons. Additionally, we observed that neurons with the genome of one sAD patient exhibited the phenotypes seen in familial Alzheimer's disease samples. More generally, we demonstrate that iPSC technology can be used to observe phenotypes relevant to Alzheimer's disease, even though it can take decades for overt disease to manifest in patients

The effects of pea peptides on the quality of set yogurt

Objective: This study aimed to reduce the setting time of yogurt, improve the texture of yogurt and evaluate the effect of pea peptides on the quality of coagulated yogurt. Methods: Different amounts（0, 0.50%, 0.75%, 1.00%, 1.25%, 1.50%）of pea peptides were added into milk powder to prepare pea peptide yogurt, and then the setting time, titer acidity, and texture properties of the yogurt were investigated. Results: The results showed that when the amount of pea peptides added was less than or equal to 1.25%, the yogurt setting time could be significantly shortened. When the amount of pea peptide added was 1%, the effect was significant by shortening the coagulation time for 32 min. The addition of pea peptides significantly increased the acidity of yogurt. When the addition amount of pea peptides was less than 1%, the springiness and chewiness of the yogurt were significantly reduced, and the gumminess, cohesiveness, and resilience were significantly increased, which improved the textural properties of the yogurt. Conclusion: The addition of pea peptides to the yogurt fermentation substrate can shorten the fermentation period and enhance the quality of the final product

Effect and Mechanism of Armillaria mellea 07-22 Fermentation on the Degradation of Zearalenone

This study used Armillaria mellea 07-22 as the experimental strain to degrade zearalenone (ZEN) by fungal biological fermentation. The degradation effects of Armillaria mellea on ZEN were studied, including the degradation effects of different concentrations of ZEN by the strain and the effects of different culture time, culture temperature, initial pH value and inoculation amount on the degradation of ZEN by the strain. Then the degradation mechanism was explored, the degradation effects of mycelium, fermentation supernatant and cell contents on ZEN were analyzed, and the effects of different fermentation time, pH values, and metal ions on degradation of ZEN by fermentation supernatant were studied, and the correlation between degradation effect and laccase production activity of the strain was illustrated. The results showed that Armillaria mellea 07-22 had a good degradation effect on ZEN. When the ZEN concentration was 5 μg/mL, the optimal degradation conditions were culture time of 8 days, culture temperature of 27 ℃, initial pH of 7.0, and inoculation amount of 10%. At this time, the degradation rate of ZEN was 78.72%. The degradation rates of ZEN by mycelium, fermentation supernatant and cell contents were 47.42%, 37.05% and 13.08% respectively. The extracellular enzymes secreted by Am-07-22 were the main way to degrade ZEN, and the mycelium cells also had a certain adsorption effect on ZEN. In addition, the correlation between the degradation rate of ZEN by fermentation supernatant and laccase activity was 0.973, and Cu2+ had the best promoting effect on the degradation of ZEN by fermentation supernatant

Dependence of Hippocampal Function on ERRγ-Regulated Mitochondrial Metabolism

SummaryNeurons utilize mitochondrial oxidative phosphorylation (OxPhos) to generate energy essential for survival, function, and behavioral output. Unlike most cells that burn both fat and sugar, neurons only burn sugar. Despite its importance, how neurons meet the increased energy demands of complex behaviors such as learning and memory is poorly understood. Here we show that the estrogen-related receptor gamma (ERRγ) orchestrates the expression of a distinct neural gene network promoting mitochondrial oxidative metabolism that reflects the extraordinary neuronal dependence on glucose. ERRγ−/− neurons exhibit decreased metabolic capacity. Impairment of long-term potentiation (LTP) in ERRγ−/− hippocampal slices can be fully rescued by the mitochondrial OxPhos substrate pyruvate, functionally linking the ERRγ knockout metabolic phenotype and memory formation. Consistent with this notion, mice lacking neuronal ERRγ in cerebral cortex and hippocampus exhibit defects in spatial learning and memory. These findings implicate neuronal ERRγ in the metabolic adaptations required for memory formation

Cord blood-derived neuronal cells by ectopic expression of SOX2 and c-MYC

The finding that certain somatic cells can be directly converted into cells of other lineages by the delivery of specific sets of transcrip- tion factors paves the way to novel therapeutic applications. Here we show that human cord blood (CB) CD133+ cells lose their hematopoietic signature and are converted into CB-induced neu- ronal-like cells (CB-iNCs) by the ectopic expression of the transcrip- tion factor Sox2, a process that is further augmented by the combination of Sox2 and c-Myc. Gene-expression analysis, immu- nophenotyping, and electrophysiological analysis show that CB- iNCs acquire a distinct neuronal phenotype characterized by the expression of multiple neuronal markers. CB-iNCs show the ability to fire action potentials after in vitro maturation as well as after in vivo transplantation into the mouse hippocampus. This system highlights the potential of CB cells and offers an alternative means to the study of cellular plasticity, possibly in the context of drug screening research and of future cell-replacement therapies

Exosomes and cancer immunotherapy: A review of recent cancer research

As phospholipid extracellular vesicles (EVs) secreted by various cells, exosomes contain non-coding RNA (ncRNA), mRNA, DNA fragments, lipids, and proteins, which are essential for intercellular communication. Several types of cells can secrete exosomes that contribute to cancer initiation and progression. Cancer cells and the immune microenvironment interact and restrict each other. Tumor-derived exosomes (TDEs) have become essential players in this balance because they carry information from the original cancer cells and express complexes of MHC class I/II epitopes and costimulatory molecules. In the present study, we aimed to identify potential targets for exosome therapy by examining the specific expression and mechanism of exosomes derived from cancer cells. We introduced TDEs and explored their role in different tumor immune microenvironment (TIME), with a particular emphasis on gastrointestinal cancers, before briefly describing the therapeutic strategies of exosomes in cancer immune-related therapy

Comparison of soil erosion models used to study the Chinese Loess Plateau

The Loess Plateau suffers from severe soil erosion that leads to a series of ecological and economic problems such as reduced land productivity, exacerbated rural poverty, decreased biodiversity and sedimentation of the riverbed in the lower reaches of the Yellow River. Soil erosion models are commonly used on the Loess Plateau to help target sustainable land management strategies to control soil erosion. In this study, we compared eleven soil erosion models that were previously used on the Loess Plateau. We studied their prediction accuracy, process representation, data and calibration requirements, and potential application in scenario studies. The selected models consisted of a broad range of model types, structures and scales. The comparison showed that process-based and empirical models did not necessarily yield more accurate results over one another for the Loess Plateau. Among the process-based models, Si’ model, WEPP and MMF had the highest prediction accuracy. However, some of the selected models were tested with total sediment load while others were tested with suspended sediment load (i.e. bedload is not included), which is subject to several drawbacks. Research questions that each of the models can address on the Loess Plateau were suggested. Further improvement of soil erosion models for the Loess Plateau should concentrate on enhancing the quality of data for model implementation and testing, incorporating key processes into process-based models according to their aims and scales, comparing models that address the same research questions, and implementing internal and spatial model testing