Activation of Serotonin 2C Receptors in Dopamine Neurons Inhibits Binge-like Eating in Mice

Acknowledgments and Disclosures This work was supported by the National Institutes of Health (Grant Nos. R01DK093587 and R01DK101379 [to YX], R01DK092605 to [QT], R01DK078056 [to MM]), the Klarman Family Foundation (to YX), the Naman Family Fund for Basic Research (to YX), Curtis Hankamer Basic Research Fund (to YX), American Diabetes Association (Grant Nos. 7-13-JF-61 [to QW] and 1-15-BS-184 [to QT]), American Heart Association postdoctoral fellowship (to PX), Wellcome Trust (Grant No. WT098012 [to LKH]), and Biotechnology and Biological Sciences Research Council (Grant No. BB/K001418/1 [to LKH]). The anxiety tests (e.g., open-field test, light-dark test, elevated plus maze test) were performed in the Mouse Neurobehavior Core, Baylor College of Medicine, which was supported by National Institutes of Health Grant No. P30HD024064. PX and YH were involved in experimental design and most of the procedures, data acquisition and analyses, and writing the manuscript. XC assisted in the electrophysiological recordings; LV-T assisted in the histology study; XY, KS, CW, YY, AH, LZ, and GS assisted in surgical procedures and production of study mice. MGM, QW, QT, and LKH were involved in study design and writing the manuscript. YX is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. The authors report no biomedical financial interests or potential conflicts of interest.Peer reviewedPublisher PD

Estrogen receptor–α in medial amygdala neurons regulates body weight

Estrogen receptor–α (ERα) activity in the brain prevents obesity in both males and females. However, the ERα-expressing neural populations that regulate body weight remain to be fully elucidated. Here we showed that single-minded–1 (SIM1) neurons in the medial amygdala (MeA) express abundant levels of ERα. Specific deletion of the gene encoding ERα (Esr1) from SIM1 neurons, which are mostly within the MeA, caused hypoactivity and obesity in both male and female mice fed with regular chow, increased susceptibility to diet-induced obesity (DIO) in males but not in females, and blunted the body weight–lowering effects of a glucagon-like peptide-1–estrogen (GLP-1–estrogen) conjugate. Furthermore, selective adeno-associated virus-mediated deletion of Esr1 in the MeA of adult male mice produced a rapid body weight gain that was associated with remarkable reductions in physical activity but did not alter food intake. Conversely, overexpression of ERα in the MeA markedly reduced the severity of DIO in male mice. Finally, an ERα agonist depolarized MeA SIM1 neurons and increased their firing rate, and designer receptors exclusively activated by designer drug–mediated (DREADD-mediated) activation of these neurons increased physical activity in mice. Collectively, our results support a model where ERα signals activate MeA neurons to stimulate physical activity, which in turn prevents body weight gain

Estrogens stimulate serotonin neurons to inhibit binge-like eating in mice

Binge eating afflicts approximately 5% of US adults, though effective treatments are limited. Here, we showed that estrogen replacement substantially suppresses binge-like eating behavior in ovariectomized female mice. Estrogen-dependent inhibition of binge-like eating was blocked in female mice specifically lacking estrogen receptor-α (ERα) in serotonin (5-HT) neurons in the dorsal raphe nuclei (DRN). Administration of a recently developed glucagon-like peptide-1–estrogen (GLP-1–estrogen) conjugate designed to deliver estrogen to GLP1 receptor–enhanced regions effectively targeted bioactive estrogens to the DRN and substantially suppressed binge-like eating in ovariectomized female mice. Administration of GLP-1 alone reduced binge-like eating, but not to the same extent as the GLP-1–estrogen conjugate. Administration of ERα-selective agonist propylpyrazole triol (PPT) to murine DRN 5-HT neurons activated these neurons in an ERα-dependent manner. PPT also inhibited a small conductance Ca2+-activated K+ (SK) current; blockade of the SK current prevented PPT-induced activation of DRN 5-HT neurons. Furthermore, local inhibition of the SK current in the DRN markedly suppressed binge-like eating in female mice. Together, our data indicate that estrogens act upon ERα to inhibit the SK current in DRN 5-HT neurons, thereby activating these neurons to suppress binge-like eating behavior and suggest ERα and/or SK current in DRN 5-HT neurons as potential targets for anti-binge therapies

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Optimum water supplement strategy to restore reed wetland in the Yellow River Delta

In order to supply optimum water to restore reed wetlands used for bird habitats, a field investigation and greenhouse experiment were conducted. Three water supplementation stages (early stage at 20 May, middle stage at 20 July and later stage at 20 September, respectively) and five depths (0, 10, 15, 20 and 35 cm over the surface, respectively) were established, with three replicates for each treatment combination. Reed growth characteristics (survival rate, height, density and biomass) and soil properties of field investigation and experiment were recorded to determine the impacts of water supplementation on reed wet-land restoration. The field investigation showed that reeds in natural wetlands grow better than those in degraded wetlands and soil properties in degraded wetlands were significantly different from soils in natural wetlands. With freshwater supplementation, reed growth characteristics and soil properties greatly improved. As water depth increased, reed growth decreased gradually. Reeds grew best in shallow water depth (<= 10cm) than in the greater flooding depths. Saturated soils with no standing water at the early stage of reed growth increased reed survival and water depth can be increased as the reeds grow. During the process of water supplementation, soil salinity was reduced significantly. Soil salinity was reduced dramatically at early and middle stages of reed growth, but it increased slightly at the later stage. Soil pH increased greatly during the experiment. Soil total nitrogen (TN) and total organic carbon (TOC) showed contrasting changes, with soil TN decreasing and TOC increasing. To best manage reed wetlands restoration, we suggest saturating wetland in the spring to stimulate reed germination, increasing surface water depth up to 15cm at the stage of reed rapid growth, and then reducing water depth during the later growth stage

Plant growth and diversity performance after restoration in Carex schmidtii tussock wetlands, Northeast China

Plant performance, which considers plant growth, community composition, and diversity, demonstrated the wetland plants’ restoration efficiency of wetland plants following restoration. Carex tussocks are widespread in temperate freshwater wetlands and streams, well as characterizing with rich biodiversity. However, tussock wetlands sharply shrank and plant performance has changed due to the interaction of long-term drought, and human disturbance (road construction, grazing and mowing). In recent decades, ecological restoration has been widely conducted in degraded tussock wetlands in semi-arid area. A field investigation was done in a restored tussock wetland (R) after restoration for 10 years in order to evaluate efficacy of tussock restoration. Tussock wetlands were chosen as reference wetlands, both natural (N) and degraded (D). In semi-arid zones, the results showed that wetlands were affected by drought and flooding. After 10 years, wetland restoration effectively restored the growth and yield of Carex schmidtii tussocks compared to D, but did not reach to the natural state. The importance value (IV) of C. schmidtii has sharply decreased in R. Xerophyte species (Artemisia integrifolia) have occupied dominant position growth. Furthermore, the IV of other wetland species has dropped through time, and some have even disappeared as a result of drought and flooding. R and N have much lower species richness and Shannon–Wiener index than D. Flooding in August, following a drought, boosted the Simpson index and Evenness index in R and N. Obvious differences in species composi- tion and community structure were found using principal component analysis among N, R, and D. Ecological restoration substantially alleviated wetland degradation in the semi-arid zone, but subsequent hydrological management is required to further promote plant growth and diversity performance

Transfer of multiple loci of donor's genes to induce recipient tolerance in organ transplantation

Donor organ rejection remains a significant problem. The present study aimed to assess whether transferring a donor's major histocompatibility complex (MHC) genes to the recipient could mitigate rejection in organ transplantation. Seven loci of MHC genes from donor mice were amplified and ligated into vectors; the vectors either contained one K locus, seven loci or were empty (control). The vectors were subsequently injected into the thymus of recipients (in heterotransplants, recipient rats received the vector containing one K locus), following which donor mouse hearts were transplanted. Following the transplantation of allograft and heterograft, electrocardiosignals were viable for a significantly longer duration in recipient mice and rats receiving the donor histocompatibility-2 complex (H-2)d genes compared with those in controls, and in mice that received seven vectors compared with those receiving one vector. Mixed lymphocyte cultures containing cells from these recipients proliferated significantly less compared with mixed lymphocyte cultures containing controls. Also, hearts from H-2d genes-treated recipients demonstrated less lymphocyte infiltration and necrosis compared with the control recipient. The present study concluded that allograft and heterograft rejection may be mitigated by introducing the donor's MHC into the recipient; transferring seven loci has been demonstrated to be more effective than transferring one locus

Study area of the Yellow River Delta.

<p>Study area of the Yellow River Delta.</p

Reed characteristics and soil properties in natural and degraded reed wetlands.

<p>Reed characteristics and soil properties in natural and degraded reed wetlands.</p