Menstrual blood losses and body mass index are associated with serum ferritin concentrations among female varsity athletes.

Preventing and treating iron deficiency are important components in the nutritional care of female varsity athletes, as these interventions may improve aerobic endurance and athletic performance. We examined the factors associated with ferritin concentration in 30 female varsity athletes (18-30 years) at the University of British Columbia in Vancouver, Canada. Biochemical indicators of iron and inflammation status, dietary intake, supplementation practices, weight, height, and menstrual blood losses were assessed. Iron deficiency prevalence was 20% (n = 6/30; inflammation-adjusted ferritin <15 µg/L). Multiple linear regression was used to assess the associations of a number of independent explanatory variables with log-transformed serum ferritin (µg/L) as the continuous outcome variable. A 1-unit increase in body mass index (BMI; kg/m2) was associated with 22% (95% CI: 9%-37%) higher mean ferritin concentrations, and a 1-point increase in menstrual loss score was associated with 1% (95% CI: 1%-2%) lower ferritin concentrations. Hemoglobin and hepcidin concentrations, inflammation biomarkers, consumption of iron supplements in any form or dose for ≥3 days/week, and age were not significantly associated with ferritin concentrations in the final adjusted model. Novelty Estimated monthly menstrual losses and BMI were associated with serum ferritin concentrations in female athletes in our study. These are easy-to-measure, noninvasive measurements that should be considered in the assessment of risk of iron deficiency in female athletes.

Glutamate Afferents From the Medial Prefrontal Cortex Mediate Nucleus Accumbens Activation by Female Sexual Behavior.

Low levels of desire and arousal are the primary sexual dysfunctions in women, necessitating neurobiological studies of sexual motivation in female animal models. As the mesocorticolimbic system is a primary neural circuit underlying sexual motivation, the goal of this study was to test the hypothesis that medial prefrontal cortex (mPFC) glutamate mediates sexual behavior activation of the nucleus accumbens. Glutamatergic neurons in the mPFC were activated by sex behavior, and these sex-activated cells shown to project to the nucleus accumbens. During sexual interactions with the male, glutamate transients recorded in the nucleus accumbens of female hamsters were specifically associated with the receipt of intromissions from the male. Further, inhibition of the mPFC during sex significantly decreased nucleus accumbens activation. Glutamatergic medial prefrontal cortical input to the nucleus accumbens mediates the activity in the nucleus accumbens during female sexual behavior. These results offer novel insights into the neurobiology of the motivational control of female sexual behavior and provide attractive avenues for pursuing target-specific and clinically-relevant therapies for sexual dysfunction in women.

mGluR5 Mediates Dihydrotestosterone-Induced Nucleus Accumbens Structural Plasticity, but Not Conditioned Reward.

Gonadal hormones play a vital role in driving motivated behavior. They not only modulate responses to naturally rewarding stimuli, but also influence responses to drugs of abuse. A commonality between gonadal hormones and drugs of abuse is that they both impact the neurocircuitry of reward, including the regulation of structural plasticity in the nucleus accumbens (NAc). Previous hormonal studies have focused on the mechanisms and behavioral correlates of estradiol-induced dendritic spine changes in the female NAc. Here we sought to determine the effects of androgens on medium spiny neuron (MSN) spine plasticity in the male NAc. Following treatment with the androgen receptor agonist dihydrotestosterone (DHT), MSNs in castrated male rats exhibited a significant decrease in dendritic spine density. This effect was isolated to the shell subregion of the NAc. The effect of DHT was dependent on mGluR5 activity, and local mGluR5 activation and subsequent endocannabinoid signaling produce an analogous NAc shell spine decrease. Somewhat surprisingly, DHT-induced conditioned place preference remained intact following systemic inhibition of mGluR5. These findings indicate that androgens can utilize mGluR signaling, similar to estrogens, to mediate changes in NAc dendritic structure. In addition, there are notable differences in the direction of spine changes, and site specificity of estrogen and androgen action, suggesting sex differences in the hormonal regulation of motivated behaviors.

Measuring In Vivo Changes in Extracellular Neurotransmitters During Naturally Rewarding Behaviors in Female Syrian Hamsters.

The ability to measure neurotransmitter release on a rapid time scale allows patterns of neurotransmission to be linked to specific behaviors or manipulations; a powerful tool in elucidating underlying mechanisms and circuitry. While the technique of microdialysis has been used for decades to measure nearly any analyte of interest in the brain, this technique is limited in temporal resolution. Alternatively, fast scan cyclic voltammetry is both temporally precise and extremely sensitive; however, because this technically difficult method relies on the electroactivity of the analyte of interest, the possibility to detect nonelectroactive substances (e.g., the neurotransmitter glutamate) is eliminated. This paper details the use of a turn-key system that combines fixed-potential amperometry and enzymatic biosensing to measure both electroactive and nonelectroactive neurotransmitters with temporal precision. The pairing of these two powerful techniques allows for the measurement of both tonic and phasic neurotransmission with relative ease, and permits recording of multiple neurotransmitters simultaneously. The aim of this manuscript is to demonstrate the process of measuring dopamine and glutamate neurotransmission in vivo using a naturally rewarding behavior (i.e., sexual behavior) in female hamsters, with the ultimate goal of displaying the technical feasibility of this assay for examining other behaviors and experimental paradigms.

Metabotropic Glutamate Receptor and Fragile X Signaling in a Female Model of Escalated Aggression.

BACKGROUND: Escalated aggression is a behavioral sign of numerous psychiatric disorders characterized by a loss of control. The neurobiology underlying escalated aggression is unknown and is particularly understudied in females. Research in our laboratory demonstrated that repeated aggressive experience in female hamsters resulted in an escalated response to future aggressive encounters and an increase in dendritic spine density on nucleus accumbens (NAc) neurons. We hypothesized that the activation of group I metabotropic glutamate receptor signaling though the fragile X mental retardation protein (FMRP) pathway may underlie synaptic plasticity associated with aggression escalation. METHODS: Female hamsters were given five daily aggression tests with or without prior treatment with the metabotropic glutamate receptor 5 (mGluR5) antagonist 2-methyl-6-(phenylethynyl)-pyridine. Following aggression testing, messenger RNA expression and protein levels were measured in the nucleus accumbens for postsynaptic density protein 95 (PSD-95) and SAP90/PSD-95-associated protein 3, as well as the levels of phosphorylated FMRP. RESULTS: Experience-dependent escalation of aggression in female hamsters depends on activation of mGluR5 receptors. Furthermore, aggressive experience decreases phosphorylation of FMRP in the NAc, which is coupled to a long-term increase in the expression of the synaptic scaffolding proteins PSD-95 and SAP90/PSD-95-associated protein 3. Finally, the experience-dependent increase in PSD-95 is prevented by antagonism of the mGluR5 receptor. CONCLUSIONS: Activation of the FMRP pathway by group I metabotropic glutamate receptors is involved in regulating synaptic plasticity following aggressive experience. The NAc is a novel target for preclinical studies of the treatment of escalated aggression, with the added benefit that emerging therapeutic approaches are likely to be effective in treating pathologic aggression in both female and male subjects.

Asymmetric Wnt Pathway Signaling Facilitates Stem Cell-Like Divisions via the Nonreceptor Tyrosine Kinase FRK-1 in Caenorhabditis elegans.

Asymmetric cell division is critical during development, as it influences processes such as cell fate specification and cell migration. We have characterized FRK-1, a homolog of the mammalian Fer nonreceptor tyrosine kinase, and found it to be required for differentiation and maintenance of epithelial cell types, including the stem cell-like seam cells of the hypodermis. A genomic knockout of frk-1, allele ok760, results in severely uncoordinated larvae that arrest at the L1 stage and have an excess number of lateral hypodermal cells that appear to have lost asymmetry in the stem cell-like divisions of the seam cell lineage. frk-1(ok760) mutants show that there are excess lateral hypodermal cells that are abnormally shaped and smaller in size compared to wild type, a defect that could be rescued only in a manner dependent on the kinase activity of FRK-1. Additionally, we observed a significant change in the expression of heterochronic regulators in frk-1(ok760) mutants. However, frk-1(ok760) mutants do not express late, nonseam hypodermal GFP markers, suggesting the seam cells do not precociously differentiate as adult-hyp7 cells. Finally, our data also demonstrate a clear role for FRK-1 in seam cell proliferation, as eliminating FRK-1 during the L3-L4 transition results in supernumerary seam cell nuclei that are dependent on asymmetric Wnt signaling. Specifically, we observe aberrant POP-1 and WRM-1 localization that is dependent on the presence of FRK-1 and APR-1. Overall, our data suggest a requirement for FRK-1 in maintaining the identity and proliferation of seam cells primarily through an interaction with the asymmetric Wnt pathway.