Cannabinoid Regulation of Nitric Oxide Synthase I (nNOS) in Neuronal Cells

In our previous studies, CB1 cannabinoid receptor agonists stimulated production of cyclic GMP and translocation of nitric oxide (NO)-sensitive guanylyl cyclase in neuronal cells (Jones et al., Neuropharmacology 54:23–30, 2008). The purpose of these studies was to elucidate the signal transduction of cannabinoid-mediated neuronal nitric oxide synthase (nNOS) activation in neuronal cells. Cannabinoid agonists CP55940 (2-[(1S,2R,5S)-5-hydroxy-2-(3-hydroxypropyl) cyclohexyl]-5-(2-methyloctan-2-yl)phenol), WIN55212-2 (R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone mesylate), and the metabolically stable analog of anandamide, (R)-(+)-methanandamide stimulated NO production in N18TG2 cells over a 20-min period. Rimonabant (N-(piperidin-lyl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-H-pyrazole-3-carboxamide), a CB1 receptor antagonist, partially or completely curtailed cannabinoid-mediated NO production. Inhibition of NOS activity (NG-nitro-l-arginine) or signaling via Gi/o protein (pertussis toxin) significantly limited NO production by cannabinoid agonists. Ca2+ mobilization was not detected in N18TG2 cells after cannabinoid treatment using Fluo-4 AM fluorescence. Cannabinoid-mediated NO production was attributed to nNOS activation since endothelial NOS and inducible NOS protein and mRNA were not detected in N18TG2 cells. Bands of 160 and 155 kDa were detected on Western blot analysis of cytosolic and membrane fractions of N18TG2 cells, using a nNOS antibody. Chronic treatment of N18TG2 cells with cannabinoid agonists downregulated nNOS protein and mRNA as detected using Western blot analysis and real-time polymerase chain reaction, respectively. Cannabinoid agonists stimulated NO production via signaling through CB1 receptors, leading to activation of Gi/o protein and enhanced nNOS activity. The findings of these studies provide information related to cannabinoid-mediated NO signal transduction in neuronal cells, which has important implications in the ongoing elucidation of the endocannabinoid system in the nervous system

The uses of outcome measures within multidisciplinary early childhood intervention services: a systematic review.

Purpose of the article: To review the use of outcome measures, across the domains of activity, participation, and environment, within multidisciplinary early childhood intervention services. MATERIALS AND METHODS: A systematic literature search was undertaken that included four electronic databases: Medline, CINAHL, EMBASE, and the Cochrane Library and Cochrane Database of Systematic Review. Inclusion criteria were age 0-24 months, having or at risk of a developmental disability, in receipt of multidisciplinary early childhood intervention services, and included outcome measures across all domains of the International Classification of Functioning-Child & Youth (ICF-CY). Only peer-reviewed journal articles were considered. Eligible studies were coded using the Oxford Levels of Evidence. Methodological quality was assessed using the Physiotherapy Evidence Database (PEDro) Scale for randomised controlled trials and the QualSyst for non-randomised control trials. RESULTS: Of the total of 5764 records identified, 10 were considered to meet inclusion criteria. CONCLUSION: Fourteen outcome measures were identified, addressing the domains of activity, participation, and environment. Of these, eight have been recommended in the early intervention literature. While the methodological quality of the 10 studies varied, these papers make a contribution to the body of research that acknowledges the role of routine and enriched environments. Implications for Rehabilitation Core practice elements of multidisciplinary early childhood intervention services indicate it is necessary to select outcome measures framed within the International Classification of Functioning-Child & Youth to inform clinical decision-making for measuring intervention effectiveness across the domains of activity, participation and environment. Of the identified measures, three (Canadian Occupational Performance Measure, Pediatric Evaluation of Disability Inventory, and Goal Attainment Scaling) are well-established and identified in the literature as multidisciplinary outcome measures for children with developmental disability. The selection of an appropriate outcome measure depends on the age of the child, individual goals of the family, and the type of intervention. This requires the combination of measures as no one measure alone will capture all components of the International Classification of Functioning-Child & Youth

Sex role similarity and sexual selection predict male and female song elaboration and dimorphism in fairy-wrens

Historically, bird song complexity was thought to evolve primarily through sexual selection on males; yet, in many species, both sexes sing and selection pressure on both sexes may be broader. Previous research suggests competition for mates and resources during short, synchronous breeding seasons leads to more elaborate male songs at high, temperate latitudes. Furthermore, we expect male-female song structure and elaboration to be more similar at lower, tropical latitudes, where longer breeding seasons and year-round territoriality yield similar social selection pressures in both sexes. However, studies seldom take both types of selective pressures and sexes into account. We examined song in both sexes in 15 populations of nine-fairy-wren species (Maluridae), a Southern Hemisphere clade with female song. We compared song elaboration (in both sexes) and sexual song dimorphism to latitude and life-history variables tied to sexual and social selection pressures and sex roles. Our results suggest that song elaboration evolved in part due to sexual competition in males: male songs were longer than female songs in populations with low male survival and less male provisioning. Also, female songs evolved independently of male songs: female songs were slower paced than male songs, although only in less synchronously breeding populations. We also found male and female songs were more similar when parental care was more equal and when male survival was high, which provides strong evidence that sex role similarity correlates with male-female song similarity. Contrary to Northern Hemisphere latitudinal patterns, male and female songs were more similar at higher, temperate latitudes. These results suggest that selection on song can be sex specific, with male song elaboration favored in contexts with stronger sexual selection. At the same time, selection pressures associated with sex role similarity appear to favor sex role similarity in song structure