Deleting Snord115 genes in mice remodels monoaminergic systems activity in the brain toward cortico-subcortical imbalances.

The neuronal-specific SNORD115 has gathered interest because its deficiency may contribute to the pathophysiology of Prader-Willi syndrome (PWS), possibly by altering post-transcriptional regulation of the gene encoding the serotonin (HTR2C) receptor. Yet, Snord115-KO mice do not resume the main symptoms of PWS, and only subtle-altered A-to-I RNA editing of Htr2c mRNAs was uncovered. Because HTR2C signaling fine-tunes the activity of monoaminergic neurons, we addressed the hypothesis that lack of Snord115 alters monoaminergic systems. We first showed that Snord115 was expressed in both monoaminergic and non-monoaminergic cells of the ventral tegmental area (VTA) and the dorsal raphe nucleus (DRN) harboring cell bodies of dopaminergic and serotonergic neurons, respectively. Measuring the tissue level of monoamines and metabolites, we found very few differences except that the content of homovanillic acid-a metabolite of dopamine-was decreased in the orbitofrontal and prefrontal cortex of Snord115-KO mice. The latter effects were, however, associated with a few changes in monoamine tissue content connectivity across the 12 sampled brain regions. Using in vivo single-cell extracellular recordings, we reported that the firing rate of VTA dopaminergic neurons and DRN serotonergic neurons was significantly increased in Snord115-KO mice. These neural circuit dysfunctions were not, however, associated with apparent defects in binge eating, conditioned place preference to cocaine, cocaine-induced hyperlocomotion or compulsive behavior. Altogether, our multiscale study shows that the absence of Snord115 impacts central monoaminergic circuits to an extent that does not elicit gross behavioral abnormalities.

Insulin modulates emotional behavior through a serotonin-dependent mechanism.

Type-2 Diabetes (T2D) is characterized by insulin resistance and accompanied by psychiatric comorbidities including major depressive disorders (MDD). Patients with T2D are twice more likely to suffer from MDD and clinical studies have shown that insulin resistance is positively correlated with the severity of depressive symptoms. However, the potential contribution of central insulin signaling in MDD in patients with T2D remains elusive. Here we hypothesized that insulin modulates the serotonergic (5-HT) system to control emotional behavior and that insulin resistance in 5-HT neurons contributes to the development of mood disorders in T2D. Our results show that insulin directly modulates the activity of dorsal raphe (DR) 5-HT neurons to dampen 5-HT neurotransmission through a 5-HT1A receptor-mediated inhibitory feedback. In addition, insulin-induced 5-HT neuromodulation is necessary to promote anxiolytic-like effect in response to intranasal insulin delivery. Interestingly, such an anxiolytic effect of intranasal insulin as well as the response of DR 5-HT neurons to insulin are both blunted in high-fat diet-fed T2D animals. Altogether, these findings point to a novel mechanism by which insulin directly modulates the activity of DR 5-HT neurons to dampen 5-HT neurotransmission and control emotional behaviors, and emphasize the idea that impaired insulin-sensitivity in these neurons is critical for the development of T2D-associated mood disorders.

Comparison of Failed and Kept General Anesthesia Appointments in a Pediatric Dental Clinic.

Purpose: To evaluate reasons pediatric dental patients missed appointments associated with general anesthesia (GA) or monitored anesthesia care (MAC).
Methods: Data were collected using a retrospective review of 518 charts of patients with appointments at a university pediatric dental clinic between January 1, 2018 and April 30, 2019. The information obtained included patient demographics and reasons for failing appointments. Statistical analyses included descriptive and bivariate analyses (alpha=0.05).
Results: A total of 518 patients were included in the study. There were 86 failed appointments (age=7.6±5.8 [standard deviation; {SD}] years; 64 percent males) and 432 kept appointments (age=8.4±7.0 [SD] years; 61.6 percent males), were included in the study. Among those patients who failed appointments, 82.6 percent had public aid (Medicaid) coverage and 47.7 percent had special health care needs (SHCN). For those who kept appointments, 80.8 percent had Medicaid coverage and 55.8 percent had SHCN. The most common reason for failed appointments was "child illness." Patients seen for emergency care between consultation and the surgery visit were more likely to fail appointments than those who were not seen for emergency care (33.3 percent versus 12.7 percent; P =0.001). Additionally, the mean/median days, respectively, between consultation and surgery for patients who missed appointments were significantly higher than for patients who kept appointments (107.5/91 days versus 75.6/58 days; P <0.001).
Conclusion: Significant differences were found between patients who failed their appointments and those who kept them.