TRAPing Ghrelin-Activated Circuits: A Novel Tool to Identify, Target and Control Hormone-Responsive Populations in TRAP2 Mice

The availability of Cre-based mouse lines for visualizing and targeting populations of hormone-sensitive cells has helped identify the neural circuitry driving hormone effects. However, these mice have limitations and may not even be available. For instance, the development of the first ghrelin receptor (Ghsr)-IRES-Cre model paved the way for using the Cre-lox system to identify and selectively manipulate ghrelin-responsive populations. The insertion of the IRES-Cre cassette, however, interfered with Ghsr expression, resulting in defective GHSR signaling and a pronounced phenotype in the homozygotes. As an alternative strategy to target ghrelin-responsive cells, we hereby utilize TRAP2 (targeted recombination in active populations) mice in which it is possible to gain genetic access to ghrelin-activated populations. In TRAP2 mice crossed with a reporter strain, we visualized ghrelin-activated cells and found, as expected, much activation in the arcuate nucleus (Arc). We then stimulated this population using a chemogenetic approach and found that this was sufficient to induce an orexigenic response of similar magnitude to that induced by peripheral ghrelin injection. The stimulation of this population also impacted food choice. Thus, the TRAPing of hormone-activated neurons (here exemplified by ghrelin-activated pathways) provides a complimentary/alternative technique to visualize, access and control discrete pathways, linking hormone action to circuit function.

A Combined Administration of Testosterone and Arginine Vasopressin Affects Aggressive Behavior in Males

Aggressive behavior is modulated by many factors, including personality and cognition, as well as endocrine and neural changes. To study the potential effects on the reaction to provocation, which was realized by an ostensible opponent subtracting money from the participant, we administered testosterone (T) and arginine vasopressin (AVP) or a respective placebo (PL). Forty males underwent a functional magnetic resonance imaging session while performing a provocation paradigm. We investigated differential hormone effects and the potential influence of Machiavellian traits on punishment choices (monetary subtractions by the participant) in the paradigm. Participants in the T/AVP group subtracted more money when they were not provoked but showed increased activation in the inferior frontal gyrus and inferior parietal lobule during feedback compared to PL. Higher Machiavellian traits significantly increased punishing behavior independent of provocation only in this group. The pilot study shows that T/AVP affects neural and behavioral responses during a provocation paradigm while personality characteristics, such as Machiavellian trait patterns, specifically interact with hormonal influences (T/AVP) and their effects on behavior.

The ulna-to-fibula ratio as a marker of organizational hormone effects on the motivational brain: A high-powered preregistered replication

Objective: We aimed at replicating findings by Köllner and Bleck (2020) regarding their proposed new marker of pubertal organizational hormone effects (OHEs), the ulna-to-fibula ratio (UFR). We tested UFR’s sex-dimorphism, independence of body height, interrelationships with other markers, and relationships to the implicit power motive (nPower) and activity inhibition (AI).Method: Our pre-registered, cross-sectional, high-powered study (N = 250; 148 women; after exclusions) included the Picture-Story Exercise (nPower, AI) and anthropometry of ulna and fibula length, facial width and height, shoulder/waist/hip circumference, and 2D:4D digit ratio.Results: UFR was sex-dimorphic (d = 0.37; outliers excluded), independent of body height, and significantly associated with other possible markers of pubertal OHEs, including facial width-to-height ratio, waist-to-hip ratio, and shoulder-to-hip ratio. As predicted, a “sex-typical” (high for men, low for women) UFR was associated with the inhibited power motive (outliers excluded). Neither nPower’s sex-dimorphic relationship with UFR, nor the sex-dimorphic relationship of the inhibited power motive with UFR asymmetry (deemed unreliable and already omitted from the preregistration) reported by Köllner and Bleck (2020) were replicated. Conclusions: Our findings bolster UFR’s status as a marker of pubertal OHEs: It is sexually dimorphic, unrelated to body height, related to other markers, and shows sex-dimorphic associations with the inhibited power motive. In conjunction with findings by Schultheiss et al. (2019) for prenatal OHEs, there is also accumulating evidence for hormonal contributions to implicit motive development.

RNA-seq Characterization of Sex-Differences in Adipose Tissue of Obesity Affected Patients: Computational Analysis of Differentially Expressed Coding and Non-Coding RNAs

Obesity is a multifactorial disease presenting sex-related differences including adipocyte functions, sex hormone effects, genetics, and metabolic inflammation. These can influence individuals’ risk for metabolic dysfunctions, with an urgent need to perform sex-based analysis to improve prevention, treatment, and rehabilitation programs. This research work is aimed at characterizing the transcriptional differences present in subcutaneous adipose tissue (SAT) of five obesity affected men versus five obesity affected women, with an additional focus on the role of long non-coding RNAs. Through RNA-sequencing, we highlighted the presence of both coding and non-coding differentially expressed RNAs, and with numerous computational analyses we identified the processes in which these genes are implicated, along with their role in co-morbidities development. We report 51 differentially expressed transcripts, 32 of which were coding genes and 19 were non-coding. Using the WGCNA R package (Weighted Correlation Network Analysis, version 1.70-3), we describe the interactions between coding and non-coding RNAs, and the non-coding RNAs association with the insurgence of specific diseases, such as cancer development, neurodegenerative diseases, and schizophrenia. In conclusion, our work highlights a specific gender sex-related transcriptional signature in the SAT of obesity affected patients.