The ASPET Mentoring Network: Enhancing Diversity and Inclusion through Career Coaching Groups within a Scientific Society.

Over the past decades, two persisting priorities in science, technology, engineering, and mathematics (STEM) training have been: 1) increasing the knowledge of and access to careers beyond academic scientist; and 2) increasing the diversity of the STEM workforce. Previous studies show that a uniquely constructed career coaching group provides strong support and progress for both priorities. This report extends this design into a more sustainable model that is positioned within the professional context of rising young scientists. This new model is based in the American Society for Pharmacology and Experimental Therapeutics (ASPET)-the ASPET Mentoring Network. Groups of PhD students and postdocs were assigned to an ASPET professional (academic or other career) member (the coach) with an initial meeting held the day before the society's annual meeting. The coaching groups interacted during the meeting and then virtually for a year. Extensive survey and interview evaluation data gathered from the first three cohorts (12 coaching groups) in 2016- 2018 provided strong evidence of the perceived and real benefits of the network. This new version of career coaching groups is both feasible and linked to career success due to its close association with a scientific society, peers, and coaches who share scientific identities and aspirations.

Differential hormonal regulation of tryptophan hydroxylase-2 mRNA in the murine dorsal raphe nucleus.

BACKGROUND: Recently a novel tryptophan hydroxylase isoform (TPH2) was identified and shown to be highly expressed in the central nervous system (CNS). Hormonal effects on TPH2 mRNA expression in the rodent dorsal raphe nucleus (DRN) are unknown. METHODS: In situ hybridization histochemistry and real-time reverse transcriptase-polymerase chain reaction (RT-PCR) were used to assess the effects of dexamethasone or estradiol on TPH2 mRNA levels in the DRN of C57/Bl6 mice. RESULTS: Dexamethasone reduced TPH2 mRNA levels in the DRN of both ovx female and intact male mice. Reduction of TPH2 mRNA in the DRN was blocked by co-administration of mifepristone. Estradiol had no detectable effect on TPH2 mRNA levels in the DRN. CONCLUSIONS: TPH2 mRNA is regulated by glucocorticoids but not estradiol in the mouse DRN. Glucocorticoid-mediated reduction of TPH2 message may have relevance to the etiology of major depression, psychotic major depression in particular, where elevated glucocorticoids are one hallmark of the disease.

Estrogen receptor-beta regulates tryptophan hydroxylase-1 expression in the murine midbrain raphe.

BACKGROUND: Distinct expression patterns of estrogen receptor (ER)-alpha and ER-beta are displayed in the murine central nervous system. ER-beta is the predominant form of the receptor expressed in the murine midbrain dorsal raphe nucleus (DRN). Tryptophan hydroxylase (TPH) is abundantly expressed in the serotonergic neurons of the DRN and is regulated by estrogen in both the monkey and the guinea pig. METHODS: In this study we used immunocytochemistry to show that ER-beta and TPH are colocalized in the serotonergic cells of the murine DRN. We utilized the ER-alpha and ER-beta gene deletion mouse models and in situ hybridization to demonstrate that ER-beta is responsible for regulating TPH1 mRNA expression. RESULTS: Estrogen increased TPH1 mRNA expression in the DRN of wild type and ER-alpha knockout mice (alpha-ERKO) but not ER-beta knockouts (beta-ERKO). CONCLUSIONS: These data indicate that ER-beta is responsible for mediating estrogen regulated TPH1 expression in the murine DRN.

Modeling an Inflammation-Related Depressive Phenotype in Mice Using Bacille Calmette-Guérin.

The relationship between inflammation and neuropsychiatric symptoms is of interest to the scientific community for several reasons. A substantial subset of patients suffering from major depressive disorder also exhibit evidence of chronic inflammation including elevated levels of circulating pro-inflammatory cytokines. Immune-mediated inflammatory diseases and immunotherapy can result in depressive symptoms in some patients. Recent evidence suggests that the chronic inflammation may play a role in the pathophysiology of the depressive state, although the specific biological mechanisms are not clear. Herein we describe a model of an inflammation-related depressive phenotype in mice using the tuberculosis vaccine, bacille Calmette-Guérin, to induce chronic inflammation and a subsequent depressive phenotype which is assessed using the tail-suspension test. The model provides an avenue to study not only the molecular and biochemical changes that may be associated with the development of the depressive phenotype, but also pharmacological manipulations of the phenotype.

A depressive phenotype induced by Bacille Calmette Guérin in 'susceptible' animals: sensitivity to antidepressants.

RATIONALE: The depressive phenotype in the BCG model of chronic inflammation has not been pharmacologically characterized. OBJECTIVES: This study aims to characterize the BCG model and establish its pharmacological sensitivity to fluoxetine, desipramine, and diazepam. MATERIALS AND METHODS: CD-1 mice were dosed with Bacille Calmette-Guérin (BCG) and measures of body weight, locomotor activity, and immobility in the tail suspension test (TST) were made. Spleen weight, plasma cytokines, and lung indoleamine-2,3-dioxygenase mRNA assessments were made at experiment termination. Pharmacological studies with acute fluoxetine and desipramine were done in naïve CD-1 mice to establish doses using the TST and in a locomotor assay to establish a nonsedating dose of diazepam. Characterization of the pharmacological sensitivity of the BCG model was done by assessing locomotor activity 6 days post BCG treatment and measuring immobility at 7 days post treatment in the presence or absence of fluoxetine (56 mg/kg), desipramine (20 mg/kg), or diazepam (1 mg/kg). RESULTS: Ten to 30 % of BCG-treated mice did not exhibit an increase in immobility and were termed "resilient" to BCG-induced behavioral changes despite evidence of an activated immune system. BCG-"susceptible" mice exhibited increased immobility in TST and deficits in locomotor activity. The increased immobility in BCG-susceptible mice was attenuated by acute fluoxetine and desipramine, and exacerbated by diazepam. CONCLUSIONS: The depressive phenotype in this BCG model of chronic inflammation is sensitive to antidepressants and consistent with clinical reports showing that paroxetine pretreatment prior to immunotherapy can prevent the development of psychiatric symptoms.