Melatonin MT1 receptors as a target for the psychopharmacology of bipolar disorder: A translational study.

The treatment of bipolar disorder (BD) still remains a challenge. Melatonin (MLT), acting through its two receptors MT1 and MT2, plays a key role in regulating circadian rhythms which are dysfunctional in BD. Using a translational approach, we examined the implication and potential of MT1 receptors in the pathophysiology and psychopharmacology of BD. We employed a murine model of the manic phase of BD (Clock mutant (ClockΔ19) mice) to study the activation of MT1 receptors by UCM871, a selective partial agonist, in behavioral pharmacology tests and in-vivo electrophysiology. We then performed a high-resolution Nuclear Magnetic Resonance study on isolated membranes to characterize the molecular mechanism of interaction of UCM871. Finally, in a cohort of BD patients, we investigated the link between clinical measures of BD and genetic variants located in the MT1 receptor and CLOCK genes. We demonstrated that: 1) UCM871 can revert behavioral and electrophysiological abnormalities of ClockΔ19 mice; 2) UCM871 promotes the activation state of MT1 receptors; 3) there is a significant association between the number of severe manic episodes and MLT levels, depending on the genetic configuration of the MT1 rs2165666 variant. Overall, this work lends support to the potentiality of MT1 receptors as target for the treatment of BD.

The Task Matters: A Comprehensive Review and Proposed Literature Score of the Effects of Chemical and Physical Parameters on Embryo Developmental Competence.

To explore the effects of chemical and physical parameters on embryo developmental competence, we conducted a systematic search on PubMed for peer-reviewed original papers using specific keywords and medical subject heading terms. Studies of interest were selected from an initial cohort of 4141 potentially relevant records retrieved. The most relevant publications were critically evaluated to identify the effect of these parameters on embryo development. Moreover, we generated a literature score (LS) using the following procedure: (i) the number of studies favoring a reference group was expressed as a fraction of all analyzed papers; (ii) the obtained fraction was multiplied by 10 and converted into a decimal number. We identified and discussed six parameters (oxygen, temperature, humidity, oil overlay, light, pH). Moreover, we generated a LS according to five different comparisons (37 °C vs. <37 °C; 5% vs. 20% oxygen; 5-2% vs. 5% oxygen; humidity conditions vs. dry conditions; light exposure vs. reduced/protected light exposure). Only two comparisons (37 °C vs. <37 °C and 5% vs. 20% oxygen) yielded a medium-high LS (8.3 and 7, respectively), suggesting a prevalence of studies in favor of the reference group (37 °C and 5% oxygen). In summary, this review and LS methodology offer semi-quantitative information on studies investigating the effects of chemical and physical parameters on embryo developmental competence.