RESUMO
We have expressed A-FOS, an inhibitor of activator protein-1 (AP-1) DNA binding, in adult mouse striatal neurons. We observed normal behavior including locomotion and exploratory activities. Following a single injection of cocaine, locomotion increased similarly in both the A-FOS expressing and littermate controls. However, following repeated injections of cocaine, the A-FOS expressing mice showed increased locomotion relative to littermate controls, an increase that persisted following a week of withdrawal and subsequent cocaine administration. These results indicate that AP-1 suppresses this behavioral response to cocaine. We analyzed mRNA from the striatum before and 4 and 24 h after a single cocaine injection in both A-FOS and control striata using Affymetrix microarrays (430 2.0 Array) to identify genes mis-regulated by A-FOS that may mediate the increased locomotor sensitization to cocaine. A-FOS expression did not change gene expression in the basal state or 4 h following cocaine treatment relative to controls. However, 24 h after an acute cocaine treatment, 84 genes were identified that were differentially expressed between the A-FOS and control mice. Fifty-six genes are down-regulated while 28 genes are up-regulated including previously identified candidates for addiction including brain-derived neurotrophic factor and period homolog 1. Using a random sample of identified genes, quantitative PCR was used to verify the microarray studies. The chromosomal location of these 84 genes was compared with human genome scans of addiction to identify potential genes in humans that are involved in addiction.
Assuntos
Transtornos Relacionados ao Uso de Cocaína/genética , Cocaína/farmacologia , Inibidores da Captação de Dopamina/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Proteína de Replicação C/metabolismo , Fatores Etários , Animais , Animais Recém-Nascidos , Comportamento Animal/efeitos dos fármacos , Mapeamento Cromossômico/métodos , Transtornos Relacionados ao Uso de Cocaína/fisiopatologia , Corpo Estriado/efeitos dos fármacos , Relação Dose-Resposta a Droga , Comportamento Exploratório/efeitos dos fármacos , Regulação da Expressão Gênica/genética , Locomoção/efeitos dos fármacos , Camundongos , Camundongos Transgênicos , Análise em Microsséries/métodos , Fosfopiruvato Hidratase/genética , Fosfopiruvato Hidratase/metabolismo , RNA Mensageiro/metabolismo , Proteína de Replicação C/genética , Fatores de TempoRESUMO
BACKGROUND: There is a significant increase in the number of HIV-infected older adults (HOA). This population may experience functional decline at a much younger age. Little is known about the relationship between functional limitations and systemic adipokines in HOA. OBJECTIVE: Our study aimed to evaluate the relationship between functional limitations and systemic adipokine levels in HOA population. DESIGN: Cross-sectional. SETTING: Academic hospital-based infectious disease clinic. PARTICIPANTS: The study investigated community-dwelling HIV-infected adults >50 years old and compared this group with age, gender and BMI comparable healthy controls. MEASUREMENTS: We measured functional status, body composition and plasma concentrations of adipokines. RESULTS: Fifty-four HOA were studied (mean: age 57 years, BMI 29 kg/m2, CD4 604, duration of HIV 17 years) and compared with thirty-two age, gender and BMI comparable healthy controls. The HOA group showed significantly higher functional limitations compared to the age, gender and BMI comparable controls (p<0.05). Levels of adipokines were significantly different between the two groups (p<0.05). Multiple regression analyses indicated that adiponectin and visfatin were significantly correlated with several physical function measures after controlling for age, sex, and metabolic comorbidities. Adiponectin was negatively correlated with functional limitations, and this relationship was stronger in the control group compared to the HOA group. Conversely, visfatin was positively correlated with functional limitations only in the HOA group. CONCLUSION: HOA have significant functional limitations and alteration in adipokine levels compared to controls. Adiponectin and visfatin were associated with functional limitations. Visfatin was a correlate of physical function only in the HOA group. Prospective longitudinal studies could provide further insight on the role of adipokines in HIV-related functional decline.
RESUMO
A secreted glycoprotein (GP) with apparent molecular mass of 90 kDa produced by cultured embryonic cells of Drosophila melanogaster was isolated and partially characterized. GP is enriched by Ser + Thr and Pro residues that constitute up to 30% of the total number of amino acids. An abundant carbohydrate moiety (40% of molecular mass) is mainly represented by vertebrate mucin-type O-linked disaccharide units Gal(beta 1-3)-GalNAc, occupying about a half of the total number of Ser+Thr residues and rendering the GP molecule high resistance to protease action. A few of N-glycans are also present in GP. These characteristics allow to consider the Drosophila GP (termed 'mucin-D') as a first representative of invertebrate mucin-type glycoproteins.