The melanocortin system regulates body pigmentation and social behaviour in a colour polymorphic cichlid fish.

The melanocortin system is a neuroendocrine system that regulates a range of physiological and behavioural processes. We examined the extent to which the melanocortin system simultaneously regulates colour and behaviour in the cichlid fish Astatotilapia burtoni We found that yellow males are more aggressive than blue males, in line with previous studies. We then found that exogenous α-melanocyte-stimulating hormone (α-MSH) increases yellowness of the body and dispersal of xanthophore pigments in both morphs. However, α-MSH had a morph-specific effect on aggression, with only blue males showing an increase in the rate of aggression. Exogenous agouti signalling peptide (ASIP), a melanocortin antagonist, did not affect coloration but reduced the rate of aggression in both colour morphs. Blue males had higher cortisol levels than yellow males. Neural gene expression of melanocortin receptors (mcr) and ligands was not differentially regulated between colour morphs. In the skin, however, mc1r and pro-opiomelanocortin (pomc) ß were upregulated in blue males, while asip 1 was upregulated in yellow males. The effects of α-MSH on behaviour and body coloration, combined with morph-specific regulation of the stress response and the melanocortin system, suggest that the melanocortin system contributes to the polymorphism in behaviour and coloration in A. burtoni.

Antisense oligonucleotide therapy rescues disturbed brain rhythms and sleep in juvenile and adult mouse models of Angelman syndrome.

UBE3A encodes ubiquitin protein ligase E3A, and in neurons its expression from the paternal allele is repressed by the UBE3A antisense transcript (UBE3A-ATS). This leaves neurons susceptible to loss-of-function of maternal UBE3A. Indeed, Angelman syndrome, a severe neurodevelopmental disorder, is caused by maternal UBE3A deficiency. A promising therapeutic approach to treating Angelman syndrome is to reactivate the intact paternal UBE3A by suppressing UBE3A-ATS. Prior studies show that many neurological phenotypes of maternal Ube3a knockout mice can only be rescued by reinstating Ube3a expression in early development, indicating a restricted therapeutic window for Angelman syndrome. Here, we report that reducing Ube3a-ATS by antisense oligonucleotides in juvenile or adult maternal Ube3a knockout mice rescues the abnormal electroencephalogram (EEG) rhythms and sleep disturbance, two prominent clinical features of Angelman syndrome. Importantly, the degree of phenotypic improvement correlates with the increase of Ube3a protein levels. These results indicate that the therapeutic window of genetic therapies for Angelman syndrome is broader than previously thought, and EEG power spectrum and sleep architecture should be used to evaluate the clinical efficacy of therapies.

Effect of chronic maternal methadone therapy on intrapartum fetal heart rate patterns.

OBJECTIVE: Treatment of maternal opioid dependence with methadone is associated with a delay in fetal heart rate (FHR) accelerations in nonstress tests. The objective of this investigation was to determine the effect of methadone maintenance therapy on intrapartum FHR patterns. METHODS: This retrospective cohort study compared intrapartum FHR tracings from 56 methadone-treated patients > or =36 weeks gestation with a control group of nonsubstance using patients matched for maternal age, parity, gestational age, and ethnicity. Blinded FHR interpretation included the recording of baseline, variability, accelerations, and late or severe variable decelerations. The 8-point FHR scoring system was based on the National Institute of Child Health and Human Development Research Planning Workshop guidelines. We considered a 25% reduction in the score during the latent phase to be significant. RESULTS: The median maintenance dose of methadone was 70 mg daily, with a range between 20 mg and 130 mg. Each patient tested negative for other substances on urine screening before admission. The significantly lower FHR score in the methadone group (mean difference, 1.4; 95% confidence interval, 1.1 to 1.7) was attributed to a lower baseline (P <.05), less moderate or marked variability (P <.01), and a lower proportion of accelerations during the first stage of labor (P <.01). A higher proportion of methadone-exposed fetuses had late or severe variable decelerations in the second stage (44.2% vs 22.9%; P <.03). Analgesic needs, operative vaginal or cesarean delivery rates, and Apgar scores less than 7 at 1 and 5 minutes were not significantly different between the two groups. CONCLUSIONS: Chronic maternal methadone treatment affects intrapartum FHR patterns by reducing the variability, baseline, and proportion of accelerations during the first stage. These subtle drug-induced effects do not compromise intrapartum decision-making or immediate newborn adjustments.