Glutamatergic and dopaminergic neurons mediate anxiogenic and anxiolytic effects of CRHR1

The corticotropin-releasing hormone receptor 1 (CRHR1) critically controls behavioral adaptation to stress and is causally linked to emotional disorders. Using neurochemical and genetic tools, we determined that CRHR1 is expressed in forebrain glutamatergic and γ-aminobutyric acid-containing (GABAergic) neurons as well as in midbrain dopaminergic neurons. Via specific CRHR1 deletions in glutamatergic, GABAergic, dopaminergic, and serotonergic cells, we found that the lack of CRHR1 in forebrain glutamatergic circuits reduces anxiety and impairs neurotransmission in the amygdala and hippocampus. Selective deletion of CRHR1 in midbrain dopaminergic neurons increases anxiety-like behavior and reduces dopamine release in the prefrontal cortex. These results define a bidirectional model for the role of CRHR1 in anxiety and suggest that an imbalance between CRHR1-controlled anxiogenic glutamatergic and anxiolytic dopaminergic systems might lead to emotional disorders.     

Spatio-temporal dynamics of bacterial communities associated with two plant species differing in organic acid secretion: A one-year microcosm study on lupin and wheat

Plants are generally assumed to influence the surrounding soil microflora through rhizodeposition. However, the role of rhizodeposits, and especially organic acids, in structuring the bacterial communities is still poorly understood. In this study, we asked the question whether plants differing in organic acid secretion have a different impact on the soil bacterial communities, and if this is the case, to which extent this impact is due to different organic acid concentrations in the rhizosphere. To investigate this question, we compared white lupin and wheat. The former is a high organic acid-secreting species, while the latter secretes only low amounts of carboxylates. We grew the plants in large microcosms including root-free control compartments for one year (replanted every second month) and analyzed the spatio-temporal changes in soil ATP concentrations, as well as in diversity and structure of bacterial communities (using DNA- and RNA-based DGGE) along a root-soil gradient after two, six and twelve month's cultivation. Our results showed: i) that white lupin and wheat differed in their impact on soil ATP concentrations and on the structure of root bacterial communities; ii) that cultivation time was a key factor in explaining the observed differences in all the parameters studied; and iii) that the amounts of organic acids accounted for a significant proportion (15%) of the variability within root active communities. These results indicate that plants influence their associated bacterial communities in a species-specific way and that for communities living in the direct vicinity of roots (rhizoplane-endorhizosphere), a significant part of this influence can be attributed to root-secreted organic acids.     

Color, betalain pattern, and antioxidant properties of cactus pear (Opuntia spp.) clones

Total phenolics, ascorbic acid, and betalain contents of differently colored cactus pear clones (nine Opuntia ficus-indica [L.] Mill. clones and one O. robusta Wendl. clone) were investigated and related to their respective antioxidant potential assessed by Trolox-equivalent antioxidant capacity (TEAC) and oxygen radical absorbance capacity (ORAC) assays. TEAC and ORAC values were very highly correlated with each other and also with values for total phenolics, betalain contents, and ascorbic acid concentrations. Total phenolics had the greatest contribution to ORAC and TEAC values. High-performance liquid chromatography (HPLC)-diode array detector (DAD)-tandem mass spectrometry (MS/MS) measurements of cactus pear juices permitted the differentiation of the clones based on variations in pigment patterns and betalain concentrations. The red and yellow betalains were absent in lime green colored cactus fruits. The ratio and concentration of these pigments were responsible for the yellow, orange, red, and purple colors in the other clones. Progeny of purple and lime green colored parents were characterized by 12% and 88% of plants bearing lime green and purple fruit, respectively. This implies that the genes for betalain production were lacking in the lime green fruits but could be provided by a parent with a complete set of genes, that is, purple fruits. Besides known pigments typical of Cactaceae, two unexpected betalains were identified. Whereas gomphrenin I was found for the first time in tissues of cactus plants, methionine-betaxanthin has never been described before as a genuine betalain. In addition to their alleged health-promoting properties, various combinations of yellow betaxanthins and red-purple betacyanins may allow the development of new food products without using artificial colorants.     

Noncanonical TGFβ signaling contributes to aortic aneurysm progression in Marfan syndrome mice

Transforming growth factor-β (TGFβ) signaling drives aneurysm progression in multiple disorders, including Marfan syndrome (MFS), and therapies that inhibit this signaling cascade are in clinical trials. TGFβ can stimulate multiple intracellular signaling pathways, but it is unclear which of these pathways drives aortic disease and, when inhibited, which result in disease amelioration. Here we show that extracellular signal-regulated kinase (ERK) 1 and 2 and Smad2 are activated in a mouse model of MFS, and both are inhibited by therapies directed against TGFβ. Whereas selective inhibition of ERK1/2 activation ameliorated aortic growth, Smad4 deficiency exacerbated aortic disease and caused premature death in MFS mice. Smad4-deficient MFS mice uniquely showed activation of Jun N-terminal kinase-1 (JNK1), and a JNK antagonist ameliorated aortic growth in MFS mice that lacked or retained full Smad4 expression. Thus, noncanonical (Smad-independent) TGFβ signaling is a prominent driver of aortic disease in MFS mice, and inhibition of the ERK1/2 or JNK1 pathways is a potential therapeutic strategy for the disease.