Influence on the cellular organization in central nervous system micromass cultures

The effects of lead on cellular neuronal development and organization have been studied. Rat embryo midbrain micromass cultures were exposed to lead acetate (0.1—5.0 ag/ml) for five days. Differentiation was indicated by the formation of neuronal foci in the cultures. Effects on cell growth and survival were estimated using a neutral red staining method. Lead was found to inhibit foci formation at concentrations (0.25 and 0.5 pg/ml) which did not affect cell survival. This selective effect on neuronal development was not found for three other heavy metal compounds: trimethyltin chloride, cadmium chloride and mercury chloride. In chicken embryo midbrain micromass cultures, foei formation was inhibited by even lower concentrations of lead (0.05-0.5 ug/ml), whereas neuronal cell aggregation in cell line micromass eocultures was unaffected by lead in concentrations up to 5.0 pg/ml. It is concluded that lead causes a disturbance in the neuronal developmentin embryonic central nervous system micromass cultures by a specific and selective effect on a property only expressed in embryonic cells

Association between ASMT and autistic-like traits in children from a Swedish nationwide cohort

Persons with autism spectrum disorders (ASDs) often display low levels of melatonin, and it has been suggested that this decrease may be due to low activity of the acetylserotonin O-methyltransferase (ASMT), the last enzyme in the melatonin synthesis pathway. Moreover, genetic variants in ASMT have been associated with autism, as well as with low ASMT activity and melatonin levels, suggesting that the low ASMT activity observed in autism may partly be due to variation within the ASMT gene. In this study, we present a symptom-based approach to investigate possible associations between ASMT and autistic-like traits (ALTs) in the general population. To this end, continuous measures of ALTs were assessed in a nationally representative twin cohort (n=1771) from Sweden and six Single Nucleotide Polymorphisms (SNP) and a duplication of exon 2 to 8 in ASMT were genotyped. Our results show a nominally significant association, in girls, between one SNP (rs5949028) in the last intron of ASMT and social interaction impairments. No significant association, however, was observed with traits related to language impairment or restricted and repetitive behavior. In conclusion, our results support the possible involvement of the ASMT gene in ASDs and our finding that only one of three traits shows association suggests that genetic research may benefit from taking a symptom-specific approach to identify genes involved in autism psychopathology.VetenskapsrådetAccepte

The observed association between maternal anxiety and adolescent asthma : children of twin design suggest familial effects

BACKGROUND: Previous studies indicate that maternal anxiety is associated with asthma in the adolescent child, but mechanisms are unclear. OBJECTIVE: To investigate the association between maternal anxiety and maternal, self- and register-based report of asthma in the adolescent child, and whether the association remains after control of familial confounding (shared environmental and genetic factors). METHOD: From the Twin and Offspring Study of Sweden, 1691 mothers (1058 twins) and their adolescent child were included. The association between maternal self-reported anxiety (Beck Anxiety Inventory (BAI) and Karolinska Scales of Personality (KSP) somatic or psychic anxiety) and asthma based on subjective (maternal or child report) or objective (register-based diagnosis and medication) measures were analysed using logistic regression. The children-of-twins design was used to explore whether genes or environment contribute to the association. RESULTS: Maternal BAI anxiety (OR 2.02, CI 1.15-3.55) was significantly associated with adolescent asthma reported by the mother. Maternal KSP somatic anxiety (OR 1.74, CI 1.04-2.91) and psychic anxiety (OR 1.74, CI 1.05-2.86) was significantly associated with breathlessness reported by the adolescent child. In contrast, maternal anxiety was not associated with increased risk for the register-based outcomes of asthma diagnosis or medication. The results remained also after adjusting for covariates and the children-of-twins analyses which indicate that the association was due to familial confounding. CONCLUSIONS: We found some associations between maternal anxiety and subjectively reported offspring asthma or breathlessness which may be due to familial effects. A likely candidate for explaining this familial confounding is heritable personality traits associated with both anxiety and subjective measures of asthma.NonePublishe

The Swedish Twin Registry : establishment of a biobank and other recent developments

The Swedish Twin Registry (STR) today contains more than 194,000 twins and more than 75,000 pairs have zygosity determined by an intra-pair similarity algorithm, DNA, or by being of opposite sex. Of these, approximately 20,000, 25,000, and 30,000 pairs are monozygotic, same-sex dizygotic, and opposite-sex dizygotic pairs, respectively. Since its establishment in the late 1950s, the STR has been an important epidemiological resource for the study of genetic and environmental influences on a multitude of traits, behaviors, and diseases. Following large investments in the collection of biological specimens in the past 10 years we have now established a Swedish twin biobank with DNA from 45,000 twins and blood serum from 15,000 twins, which effectively has also transformed the registry into a powerful resource for molecular studies. We here describe the main projects within which the new collections of both biological samples as well as phenotypic measures have been collected. Coverage by year of birth, zygosity determination, ethnic heterogeneity, and influences of in vitro fertilization are also described.VetenskapsrådetNIHSSFHjärt- och LungfondenAstma- och AllergiförbundetAccepte

Developmental Toxicity of Ochratoxin A in Rat Embryo Midbrain Micromass Cultures

Embryonic midbrain micromass cultures were exposed for five days to ochratoxin A (OTA) at seven concentrations (ranging from 0.16 to 10 μg/mL). Cell viability was assessed in neutral red uptake test (NRU), and differentiation – by immunoenzymatic determination of structural proteins (βIII-tubulin, MAP2, GFAP) expression level as well as by computer image analysis. Dose dependent decrease in cell number and differentiation was observed. Concentration-response curves were analysed and the mean inhibition concentrations (μg/mL) for cytotoxicity (IC50) and differentiation (ID50) were calculated. There were no significant differences in the sensitivity of neurons in early and late stage of differentiation and astrocytes to the toxic activity of this compound. For all endpoints ID50 value was very low (< 10 μg/mL) so OTA was classified as a strong teratogen. IC50/ ID50 ratios <2 pointed out that with harmful action of OTA the basic cytotoxicity should be connected

Homeodomain protein Otp affects developmental neuropeptide switching in oxytocin neurons associated with a long-term effect on social behavior

No supplementary materials.Proper response to stress and social stimuli depends on orchestrated development of hypothalamic neuronal circuits. Here we address the effects of the developmental transcription factor orthopedia (Otp) on hypothalamic development and function. We show that developmental mutations in the zebrafish paralogous gene otpa but not otpb affect both stress response and social preference. These behavioral phenotypes were associated with developmental alterations in oxytocinergic (OXT) neurons. Thus, otpa and otpb differentially regulate neuropeptide switching in a newly identified subset of OXT neurons that co-express the corticotropin-releasing hormone (CRH). Single-cell analysis revealed that these neurons project mostly to the hindbrain and spinal cord. Ablation of this neuronal subset specifically reduced adult social preference without affecting stress behavior, thereby uncoupling the contribution of a specific OXT cluster to social behavior from the general otpa(-/-) deficits. Our findings reveal a new role for Otp in controlling developmental neuropeptide balance in a discrete OXT circuit whose disrupted development affects social behavior.Israel Science Foundation grants: (1511/16, 957/12, 2137/16).info:eu-repo/semantics/publishedVersio

ApoB100-LDL Acts as a Metabolic Signal from Liver to Peripheral Fat Causing Inhibition of Lipolysis in Adipocytes

International audienceBACKGROUND: Free fatty acids released from adipose tissue affect the synthesis of apolipoprotein B-containing lipoproteins and glucose metabolism in the liver. Whether there also exists a reciprocal metabolic arm affecting energy metabolism in white adipose tissue is unknown. METHODS AND FINDINGS: We investigated the effects of apoB-containing lipoproteins on catecholamine-induced lipolysis in adipocytes from subcutaneous fat cells of obese but otherwise healthy men, fat pads from mice with plasma lipoproteins containing high or intermediate levels of apoB100 or no apoB100, primary cultured adipocytes, and 3T3-L1 cells. In subcutaneous fat cells, the rate of lipolysis was inversely related to plasma apoB levels. In human primary adipocytes, LDL inhibited lipolysis in a concentration-dependent fashion. In contrast, VLDL had no effect. Lipolysis was increased in fat pads from mice lacking plasma apoB100, reduced in apoB100-only mice, and intermediate in wild-type mice. Mice lacking apoB100 also had higher oxygen consumption and lipid oxidation. In 3T3-L1 cells, apoB100-containing lipoproteins inhibited lipolysis in a dose-dependent fashion, but lipoproteins containing apoB48 had no effect. ApoB100-LDL mediated inhibition of lipolysis was abolished in fat pads of mice deficient in the LDL receptor (Ldlr(-/-)Apob(100/100)). CONCLUSIONS: Our results show that the binding of apoB100-LDL to adipocytes via the LDL receptor inhibits intracellular noradrenaline-induced lipolysis in adipocytes. Thus, apoB100-LDL is a novel signaling molecule from the liver to peripheral fat deposits that may be an important link between atherogenic dyslipidemias and facets of the metabolic syndrome