Rodents and humans are able to detect the odour of L-Lactate.

L-Lactate (LL) is an essential cellular metabolite which can be used to generate energy. In addition, accumulating evidence suggests that LL is used for inter-cellular signalling. Some LL-sensitive receptors have been identified but we recently proposed that there may be yet another unknown G-protein coupled receptor (GPCR) sensitive to LL in the brain.

Random Survival Forest in practice: a method for modelling complex metabolomics data in time to event analysis.

Background: The application of metabolomics in prospective cohort studies is statistically challenging. Given the importance of appropriate statistical methods for selection of disease-associated metabolites in highly correlated complex data, we combined random survival forest (RSF) with an automated backward elimination procedure that addresses such issues.

Methods: Our RSF approach was illustrated with data from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study, with concentrations of 127 serum metabolites as exposure variables and time to development of type 2 diabetes mellitus (T2D) as outcome variable.

Omentin-1 and risk of myocardial infarction and stroke: Results from the EPIC-Potsdam cohort study.

Background And Aims: The recently identified adipokine omentin-1 is inversely associated with body fatness, metabolic syndrome and cardiovascular disease (CVD) in cross-sectional analyses. However, prospective data on the association between plasma omentin-1 levels and future risk of CVD are lacking. The aim of the study was to investigate the relationship between omentin-1 and incident myocardial infarction (MI) and stroke.

Identification of Serum Metabolites Associated With Incident Hypertension in the European Prospective Investigation into Cancer and Nutrition-Potsdam Study.

Metabolomics is a promising tool to gain new insights into early metabolic alterations preceding the development of hypertension in humans. We therefore aimed to identify metabolites associated with incident hypertension using measured data of serum metabolites of the European Prospective Investigation Into Cancer and Nutrition (EPIC)-Potsdam study. Targeted metabolic profiling was conducted on serum blood samples of a randomly drawn EPIC-Potsdam subcohort consisting of 135 cases and 981 noncases of incident hypertension, all of them being free of hypertension and not on antihypertensive therapy at the time of blood sampling.

Pharmacological Interference With Protein-protein Interactions of Akinase Anchoring Proteins as a Strategy for the Treatment of Disease.

A-kinase anchoring proteins (AKAPs) control the localization of cAMP-dependent protein kinase A (PKA) by tethering PKA to distinct cellular compartments. Through additional direct proteinprotein interactions with PKA substrates and other signaling molecules they form multi-protein complexes. Thereby, AKAPs regulate the access of PKA to its substrates in a temporal and spatial manner as well as the local crosstalk of cAMP/PKA with other signaling pathways.

Spatio-temporal model of endogenous ROS and raft-dependent WNT/beta-catenin signaling driving cell fate commitment in human neural progenitor cells.

Canonical WNT/β-catenin signaling is a central pathway in embryonic development, but it is also connected to a number of cancers and developmental disorders. Here we apply a combined in-vitro and in-silico approach to investigate the spatio-temporal regulation of WNT/β-catenin signaling during the early neural differentiation process of human neural progenitors cells (hNPCs), which form a new prospect for replacement therapies in the context of neurodegenerative diseases. Experimental measurements indicate a second signal mechanism, in addition to canonical WNT signaling, being involved in the regulation of nuclear β-catenin levels during the cell fate commitment phase of neural differentiation.

Screening for small molecule disruptors of AKAP-PKA interactions.

Protein-protein interactions (PPIs) are highly specific and diverse. Their selective inhibition with peptides, peptidomimetics, or small molecules allows determination of functions of individual PPIs. Moreover, inhibition of disease-associated PPIs may lead to new concepts for the treatment of diseases with an unmet medical need.

Linking diet, physical activity, cardiorespiratory fitness and obesity to serum metabolite networks: findings from a population-based study.

Objective: It is not yet resolved how lifestyle factors and intermediate phenotypes interrelate with metabolic pathways. We aimed to investigate the associations between diet, physical activity, cardiorespiratory fitness and obesity with serum metabolite networks in a population-based study.

Methods: The present study included 2380 participants of a randomly drawn subcohort of the European Prospective Investigation into Cancer and Nutrition-Potsdam.

Development and evaluation of a short 24-h food list as part of a blended dietary assessment strategy in large-scale cohort studies.

Background/objectives: The validity of dietary assessment in large-scale cohort studies has been questioned. Combining data sources for the estimation of usual intake in a blended approach may enhance the validity of dietary measurement. Our objective was to develop a web-based 24-h food list for Germany to identify foods consumed during the previous 24 h and to evaluate the performance of the new questionnaire in a feasibility study.

Cannabinoid receptor CB1 mediates baseline and activity-induced survival of new neurons in adult hippocampal neurogenesis.

Background: Adult neurogenesis is a particular example of brain plasticity that is partially modulated by the endocannabinoid system. Whereas the impact of synthetic cannabinoids on the neuronal progenitor cells has been described, there has been lack of information about the action of plant-derived extracts on neurogenesis. Therefore we here focused on the effects of Delta9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) fed to female C57Bl/6 and Nestin-GFP-reporter mice on proliferation and maturation of neuronal progenitor cells and spatial learning performance.

Melatonin modulates cell survival of new neurons in the hippocampus of adult mice.

Regulation of adult hippocampal neurogenesis is influenced by circadian rhythm, affected by the manipulation of sleep, and is disturbed in animal models of affective disorders. These observations and the link between dysregulation of the circadian production of melatonin and neuropsychiatric disorders prompted us to investigate the potential role of melatonin in controlling adult hippocampal neurogenesis. In vitro, melatonin increased the number of new neurons derived from adult hippocampal neural precursor cells in vitro by promoting cell survival.

Enriched monolayer precursor cell cultures from micro-dissected adult mouse dentate gyrus yield functional granule cell-like neurons.

Background: Stem cell cultures are key tools of basic and applied research in Regenerative Medicine. In the adult mammalian brain, lifelong neurogenesis originating from local precursor cells occurs in the neurogenic regions of the hippocampal dentate gyrus. Despite widespread interest in adult hippocampal neurogenesis and the use of mouse models to study it, no protocol existed for adult murine long-term precursor cell cultures with hippocampus-specific differentiation potential.

The neuregulin-I/ErbB signaling system in development and disease.

Neuregulins (NRGs) comprise a large family of EGF-like signaling molecules involved in cell-cell communication during development and disease. The neuregulin family of ligands has four members: NRG1, NRG2, NRG3, and NRG4. Relatively little is known about the biological functions of the NRG2, 3, and 4 proteins.

They are not too excited: the possible role of adult-born neurons in epilepsy.

In a new study in this issue of Neuron, Jakubs and colleagues report that adult-generated hippocampal granule cells develop particular functional properties when their birth is induced by epileptic seizures. The new neurons showed reduced excitatory synaptic input and decreased excitability. Their functional integration was thus adjusted to the prevailing functional state in the network.

Two genetic rat models of arterial hypertension show different mechanisms by which adult hippocampal neurogenesis is increased.

To investigate strain differences and genetic effects on different aspects of neurogenesis, we compared young adult spontaneously hypertensive/hyperactive rats (SHR) and stroke-prone SHR (SHRSP) with the genetic control WKY strain. In both hypertensive/hyperactive strains, the number of newly generated neurons and the number of lineage-determined cells as detected by doublecortin (DCX) immunoreactivity were significantly increased. SHRSP had significantly more DCX-positive cells than the other groups.

Variability of doublecortin-associated dendrite maturation in adult hippocampal neurogenesis is independent of the regulation of precursor cell proliferation.

Background: In the course of adult hippocampal neurogenesis most regulation takes place during the phase of doublecortin (DCX) expression, either as pro-proliferative effect on precursor cells or as survival-promoting effect on postmitotic cells. We here obtained quantitative data about the proliferative population and the dynamics of postmitotic dendrite development during the period of DCX expression. The question was, whether any indication could be obtained that the initiation of dendrite development is timely bound to the exit from the cell cycle.

Paradoxical effects of learning the Morris water maze on adult hippocampal neurogenesis in mice may be explained by a combination of stress and physical activity.

Studies in rats that assessed the relation of hippocampus-dependent learning and adult hippocampal neurogenesis suggested a direct regulatory effect of learning on neurogenesis, whereas a similar study in mice had not found such causal link. We here report a substantial decrease of BrdU-positive cells and other measures of adult hippocampal neurogenesis in mice trained in the hidden (HID) or cued version (VIS) of the Morris water maze as compared to untrained animals (CTR). Particularly, cells on advanced stages of neuronal development contributed to this decrease, whereas earlier progenitors (type 2 cells) were not diminished in HID, but were diminished in VIS as compared to CTR.

Enriched environment induces cellular plasticity in the adult substantia nigra and improves motor behavior function in the 6-OHDA rat model of Parkinson's disease.

The adult substantia nigra bears the capacity to generate new neural cells throughout adulthood. The mechanisms of cellular plasticity in this brain region remain unknown. In the adult dentate gyrus, dopamine was suggested to be one of the key players in neurogenesis.

Zinc ions are endogenous modulators of neurotransmitter-stimulated capacitative Ca2+ entry in both cultured and in situ mouse astrocytes.

Astrocytes express a variety of metabotropic receptors and their activation leads to a biphasic Ca2+ response due to Ca2+ release from intracellular stores and subsequent capacitative Ca2+ entry. We performed Ca2+ imaging with Fura-2 on cultured mouse astrocytes and showed that extracellular zinc reversibly blocks the capacitative Ca2+ entry following application of the metabotropic ligands ATP, glutamate and endothelin-1. Zinc blocked the plateau phase of the ligand-triggered Ca2+ responses.

Age-dependent expression of glucocorticoid- and mineralocorticoid receptors on neural precursor cell populations in the adult murine hippocampus.

Steroid hormones are regulators of adult hippocampal neurogenesis and are central to hypotheses regarding adult neurogenesis in age-related and psychiatric disturbances associated with altered hippocampal plasticity--most notably dementias and major depression. Using immunohistochemistry, we examined the expression of glucocorticoid (GR) and mineralocorticoid (MR) receptors during adult hippocampal neurogenesis. In young mice only 27% of dividing cells in the subgranular zone expressed GR, whereas 4 weeks after division 87% had become positive for GR and MR.

Differential regulation of gliogenesis in the context of adult hippocampal neurogenesis in mice.

In adult hippocampal neurogenesis, new neurons appear to originate from a cell with astrocytic properties expressing glial fibrillary acidic protein (GFAP). Also, new astrocytes are generated in the adult dentate gyrus. Whereas the putative astrocyte-like progenitor cells are consistently S-100beta-negative, many new astrocytes are S-100beta-positive.

Transient calretinin expression defines early postmitotic step of neuronal differentiation in adult hippocampal neurogenesis of mice.

We here show that the early postmitotic stage of granule cell development during adult hippocampal neurogenesis is characterized by the transient expression of calretinin (CR). CR expression was detected as early as 1 day after labeling dividing cells with bromodeoxyuridine (BrdU), but not before. Staining for Ki-67 confirmed that no CR-expressing cells were in cell cycle.

Subpopulations of proliferating cells of the adult hippocampus respond differently to physiologic neurogenic stimuli.

To study how adult hippocampal neurogenesis might originate from the proliferation of stem or progenitor cells in vivo, we have used transgenic mice expressing green fluorescent protein (GFP) under the nestin promoter to identify these cells. Having described an astrocyte-like type 1 cell with low proliferative activity, a characteristic morphology, vascular end feet, and passive electrophysiological properties, we focused here on the large population of nestin-GFP-expressing type 2 cells, which lack all these features. Type 2 cells were highly proliferative and showed signs suggestive of their involvement in the neuronal lineage.

Bazooka is a permissive factor for the invasive behavior of discs large tumor cells in Drosophila ovarian follicular epithelia.

Drosophila Bazooka and atypical protein kinase C are essential for epithelial polarity and adhesion. We show here that wild-type bazooka function is required during cell invasion of epithelial follicle cells mutant for the tumor suppressor discs large. Clonal studies indicate that follicle cell Bazooka acts as a permissive factor during cell invasion, possibly by stabilizing adhesion between the invading somatic cells and their substratum, the germline cells.

Characterization of microglial cells and their response to stimulation in an organotypic retinal culture system.

An organotypic culture system of the early postnatal rat retina was developed to study microglial activation within a tissue environment. One day after tissue preparation, microglial cells of the ganglion cell/nerve fiber layer revealed features of activation. Cells acquired an ameboid morphology as revealed by Bandeiraea simplicifolia lectin staining.