The Role of Osteocalcin in the Regulation of Brain Development and Functions

The central nervous system controls many physiological processes including energy metabolism, immune response, reproduction, and development. In turn, hormones synthesized in and secreted by peripheral organs can be transported across the blood-brain barrier to modulate the development of the brain, the formation of new neurons, neural activity, behavior, and the secretion of brain-derived hormones. The central control of bone mass, mediated by the adipocyte-derived hormone leptin, has raised questions of whether the skeleton may signal back to the brain. In recent years, the Karsenty laboratory has uncovered the endocrine role of the bone-derived hormone osteocalcin. Through the use of a vast array of genetic tools, the Karsenty lab has discovered that osteocalcin is a potent regulator of glucose homeostasis, adaptation to exercise, energy metabolism, and male fertility. The multifunctional role of osteocalcin led us to hypothesize that it may act as a molecular means of communication between the skeleton and the brain. We asked whether osteocalcin could regulate brain development during embryogenesis and behavioral functions in adulthood. In addressing these questions, we observed that bone-derived osteocalcin crosses the blood-brain barrier, accumulates in discrete parts of the brain including the hippocampus, and binds to several neuronal populations to favor the synthesis of monoamine neurotransmitters (serotonin, dopamine, and norepinephrine), and to impede the synthesis of the inhibitory neurotransmitter, GABA. Osteocalcin-/- mice have increased anxiety and depression and impaired learning and memory when compared to WT littermates. We also uncovered that the absence of maternal osteocalcin during embryogenesis hinders brain development and causes defects in spatial learning and memory in the adult offspring. Upon characterizing the necessity of osteocalcin for brain development and cognitive function, we investigated whether bone health is a determinant of cognition, and whether osteocalcin may be sufficient to reverse age-related cognitive decline. In addressing the first question, we found that impairment in either bone formation or bone resorption negatively impacts both anxiety and memory. In addressing the second question, we found that osteocalcin is also necessary for the beneficial effect of young blood on cognitive functions. Finally, we observed reduced anxiety and improved memory in aged mice receiving osteocalcin peripherally. This action appears to require an increase in brain-derived neurotrophic factor levels in the hippocampus. Against the backdrop of our progressively aging population, it is important for future studies to determine whether osteocalcin may act therapeutically in humans to treat age-related cognitive decline. Additionally, to identify potential drug targets, it is important to fully characterize the molecular mechanism by which osteocalcin acts on neurons

Attractant Pheromone of the Neotropical Species Neomegalotomus parvus (Westwood) (Heteroptera: Alydidae).

The Neotropical broad-headed bug, Neomegalotomus parvus (Westwood), is adapted to various leguminous crops and is considered a pest in common bean and soybean. The chemical communication of this species was studied in order to identify an attractant pheromone. Males and females of N. parvus produce several short-chain esters and acids, and their antennae showed electrophysiological responses to ?ve of these compounds, three common to both sexes (hexyl butanoate, 4-methylhexyl butanoate, and hexyl hexanoate), and two female-speci?c compounds (4-methylhexyl pentanoate and hexyl pentanoate). Both aeration extracts of females and a solution containing ?ve synthetic compounds mimicking the natural blend were attractive to males and females N. parvus in a laboratory bioassay. Aspects of the chemical ecology of the broad-headed bugs and the possibility to use pheromone-baited traps in the ?eld for monitoring are discussed

De novo formation of an aggregation pheromone precursor by an isoprenyl diphosphate synthase-related terpene synthase in the harlequin bug.

Insects use a diverse array of specialized terpene metabolites as pheromones in intraspecific interactions. In contrast to plants and microbes, which employ enzymes called terpene synthases (TPSs) to synthesize terpene metabolites, limited information from few species is available about the enzymatic mechanisms underlying terpene pheromone biosynthesis in insects. Several stink bugs (Hemiptera: Pentatomidae), among them severe agricultural pests, release 15-carbon sesquiterpenes with a bisabolene skeleton as sex or aggregation pheromones. The harlequin bug, Murgantia histrionica, a specialist pest of crucifers, uses two stereoisomers of 10,11-epoxy-1-bisabolen-3-ol as a male-released aggregation pheromone called murgantiol. We show that MhTPS (MhIDS-1), an enzyme unrelated to plant and microbial TPSs but with similarity to trans-isoprenyl diphosphate synthases (IDS) of the core terpene biosynthetic pathway, catalyzes the formation of (1S,6S,7R)-1,10-bisaboladien-1-ol (sesquipiperitol) as a terpene intermediate in murgantiol biosynthesis. Sesquipiperitol, a so-far-unknown compound in animals, also occurs in plants, indicating convergent evolution in the biosynthesis of this sesquiterpene. RNAi-mediated knockdown of MhTPS mRNA confirmed the role of MhTPS in murgantiol biosynthesis. MhTPS expression is highly specific to tissues lining the cuticle of the abdominal sternites of mature males. Phylogenetic analysis suggests that MhTPS is derived from a trans-IDS progenitor and diverged from bona fide trans-IDS proteins including MhIDS-2, which functions as an (E,E)-farnesyl diphosphate (FPP) synthase. Structure-guided mutagenesis revealed several residues critical to MhTPS and MhFPPS activity. The emergence of an IDS-like protein with TPS activity in M. histrionica demonstrates that de novo terpene biosynthesis evolved in the Hemiptera in an adaptation for intraspecific communication

Captura em campo de Thyanta perditor em armadilhas iscadas com feromônio

The objective of this work was to evaluate the field attractiveness of Thyanta perditor synthetic sex pheromone‑baited traps, its attractivity to other stink bug species, and the response of T. perditor to a geometric isomer of the sex pheromone. Two‑liter transparent plastic bottles traps were baited with rubber septa impregnated with the treatments: 1 mg of methyl‑(2E,4Z,6Z)‑decatrienoate [(2E,4Z,6Z)‑10:COOMe], the male sex pheromone of T. perditor; 1 mg of (2E,4Z,6Z)‑10:COOMe protected from sunlight in standard PVC plumbing pipe; 1 mg of its geometric isomer [(2E,4E,6Z)‑10:COOMe]; and traps with rubber septa impregnated with hexane (control). The experiment was carried out in field during the soybean reproductive stages. Traps were monitored weekly, and the captures were compared to the population density estimated by the sampling cloth and visual inspection monitoring techniques. Traps baited with the sex pheromone, protected or not, were more effective in capturing T. perditor than traps baited with the isomer or the hexane. Thyanta perditor sex pheromone showed cross‑attraction to other stink bug species, such as Euschistus heros, Edessa meditabunda, Piezodorus guildinii and Nezara viridula. Pheromone‑baited traps can be used in population monitoring and to identify the relative composition of stink bug guilds. O objetivo deste trabalho foi avaliar em campo a atratividade de armadilhas iscadas com o feromônio sexual sintético de Thyanta perditor,  a possível  atração de outras  espécies de percevejos pelo feromônio sexual e a resposta de T. perditor ao isômero geométrico de seu feromônio sexual. Armadilhas construídas com garrafas plásticas de 2 L foram iscadas com septos de borracha impregnados com os tratamentos: 1 mg de (2E,4Z,6Z)‑decatrienoato de metila [(2E,4Z,6Z)‑10:COOMe], feromônio sexual de machos de T. perditor; 1 mg de (2E,4Z,6Z)‑10:COOMe protegido da luz solar com um tubo de PVC; 1 mg do seu isômero geométrico [(2E,4E,6Z)‑10:COOMe];  e septos  de  borracha  impregnados  com  hexano (controle).  O  experimento foi conduzido em campo durante a fase reprodutiva da soja. As armadilhas foram monitoradas semanalmente, e as capturas comparadas com a densidade populacional estimada pelas técnicas de pano de batida e inspeção visual. As armadilhas iscadas com o feromônio sexual, protegido ou não, foram mais eficientes na captura de T. perditor que as armadilhas iscadas com o isômero ou com o hexano. Foi observada atração cruzada do feromônio sexual de T. perditor a outras espécies de percevejos, como Euschistus heros, Edessa meditabunda, Piezodorus guildinii e Nezara viridula. Armadilhas iscadas com o feromônio podem ser usadas no monitoramento populacional e na identificação da composição relativa de guildas de percevejos

Identification and Synthesis of a Male-Produced Pheromone for the Neotropical Root Weevil Diaprepes abbreviatus

An unsaturated hydroxy-ester pheromone was isolated from the headspace and feces of male Diaprepes abbreviatus, identified, and synthesized. The pheromone, methyl (E)-3-(2-hydroxyethyl)-4-methyl-2-pentenoate, was discovered by gas chromatography-coupled electroantennogram detection (GC-EAD), and identified by gas chromatography–mass spectrometry (GC-MS) and nuclear magnetic resonance spectroscopy (NMR). The synthesis yielded an 86:14 mixture of methyl (E)-3-(2-hydroxyethyl)-4-methyl-2-pentenoate (active) and methyl (Z)-3-(2-hydroxyethyl)-4-methyl-2-pentenoate (inactive), along with a lactone breakdown product. The activity of the synthetic E-isomer was confirmed by GC-EAD, GC-MS, NMR, and bioassays. No antennal response was observed to the Z-isomer or the lactone. In a two-choice olfactometer bioassay, female D. abbreviatus moved upwind towards the synthetic pheromone or natural pheromone more often compared with clean air. Males showed no clear preference for the synthetic pheromone. This pheromone, alone or in combination with plant volatiles, may play a role in the location of males by female D. abbreviatus

Gpr158 mediates osteocalcin's regulation of cognition

That osteocalcin (OCN) is necessary for hippocampal-dependent memory and to prevent anxiety-like behaviors raises novel questions. One question is to determine whether OCN is also sufficient to improve these behaviors in wild-type mice, when circulating levels of OCN decline as they do with age. Here we show that the presence of OCN is necessary for the beneficial influence of plasma from young mice when injected into older mice on memory and that peripheral delivery of OCN is sufficient to improve memory and decrease anxiety-like behaviors in 16-mo-old mice. A second question is to identify a receptor transducing OCN signal in neurons. Genetic, electrophysiological, molecular, and behavioral assays identify Gpr158, an orphan G protein-coupled receptor expressed in neurons of the CA3 region of the hippocampus, as transducing OCN's regulation of hippocampal-dependent memory in part through inositol 1,4,5-trisphosphate and brain-derived neurotrophic factor. These results indicate that exogenous OCN can improve hippocampal-dependent memory in mice and identify molecular tools to harness this pathway for therapeutic purposes

Data S11: Raw data for Larvae Fed Terpene Phosphates

Green lacewings (Neuroptera: Chrysopidae) are voracious predators of aphids and other small, soft-bodied insects and mites. Earlier, we identified (1R,2S,5R,8R)-iridodial from wild males of the goldeneyed lacewing, Chrysopa oculata Say, which is released from thousands of microscopic dermal glands on the abdominal sterna. Iridodial-baited traps attract C. oculata and other Chrysopa spp. males into traps, while females come to the vicinity of, but do not usually enter traps. Despite their healthy appearance and normal fertility, laboratory-reared C. oculata males do not produce iridodial. Surprisingly, goldeneyed lacewing males caught alive in iridodial-baited traps attempt to eat the lure and, in Asia, males of other Chrysopa species reportedly eat the native plant, Actinidia polygama (Siebold & Zucc.) Maxim. (Actinidiaceae) to obtain the monoterpenoid, neomatatabiol. These observations suggest that Chrysopa males must sequester exogenous natural iridoids in order to produce iridodial; we investigated this phenomenon in laboratory feeding studies. Lacewing adult males fed various monoterpenes reduced carbonyls to alcohols and saturated double bonds, but did not convert these compounds to iridodial. Only males fed the common aphid sex pheromone component, (1R,4aS,7S,7aR)-nepetalactol, produced (1R,2S,5R,8R)-iridodial. Furthermore, although C. oculata males fed the second common aphid sex pheromone component, (4aS,7S,7aR)-nepetalactone, did not produce iridodial, they did convert ∼75% of this compound to the corresponding dihydronepetalactone, and wild C. oculata males collected in early spring contained traces of this dihydronepetalactone. These findings are consistent with the hypothesis that Chrysopa males feed on oviparae (the late-season pheromone producing stage of aphids) to obtain nepetalactol as a precursor to iridodial. In the spring, however, wild C. oculata males produce less iridodial than do males collected later in the season. Therefore, we further hypothesize that Asian Chrysopa eat A. polygama to obtain iridoid precursors in order to make their pheromone, and that other iridoid-producing plants elsewhere in the world must be similarly usurped by male Chrysopa species to sequester pheromone precursors

Attraction of the Invasive Halyomorpha halys (Hemiptera: Pentatomidae) to Traps Baited with Semiochemical Stimuli Across the United States

A recent identification of the two-component aggregation pheromone of the invasive stink bug species, Halyomorpha halys (Stål), in association with a synergist, has greatly improved the ability to accurately monitor the seasonal abundance and distribution of this destructive pest. We evaluated the attraction of H. halys to black pyramid traps baited with lures containing the pheromone alone, the synergist methyl (2E,4E,6Z)-decatrienoate (MDT) alone, and the two lures in combination. Traps were deployed around areas of agricultural production including fruit orchards, vegetables, ornamentals, or row crops in Delaware, Maryland, North Carolina, New Jersey, New York, Ohio, Oregon, Pennsylvania, Virginia, and West Virginia from mid-April to mid-October, 2012 and 2013. We confirmed that H. halys adults and nymphs are attracted to the aggregation pheromone season long, but that attraction is significantly increased with the addition of the synergist MDT. H. halys adults were detected in April with peak captures of overwintering adults in mid- to late May. The largest adult captures were late in the summer, typically in early September. Nymphal captures began in late May and continued season long. Total captures declined rapidly in autumn and ceased by mid-October. Captures were greatest at locations in the Eastern Inland region, followed by those in the Eastern Coastal Plain and Pacific Northwest. Importantly, regardless of location in the United States, all mobile life stages of H. halys consistently responded to the combination of H. halys aggregation pheromone and the synergist throughout the entire season, suggesting that these stimuli will be useful tools to monitor for H. halys in managed system