Sex differences in fear extinction Velasco, E.R.; Florido, A.; Milad, M.R. ...
Neuroscience & biobehavioral reviews/Neuroscience and biobehavioral reviews,
08/2019, Volume:
103
Journal Article
Peer reviewed
Open access
Despite the exponential increase in fear research during the last years, few studies have included female subjects in their design. The need to include females arises from the knowledge gap of ...mechanistic processes underlying the behavioral and neural differences observed in fear extinction. Moreover, the exact contribution of sex and hormones in relation to learning and behavior is still largely unknown. Insights from this field could be beneficial as fear-related disorders are twice as prevalent in women compared to men. Here, we review an up-to-date summary of animal and human studies in adulthood that report sex differences in fear extinction from a structural and functional approach. Furthermore, we describe how these factors could contribute to the observed sex differences in fear extinction during normal and pathological conditions.
Memory formation is key for brain functioning. Uncovering the memory mechanisms is helping us to better understand neural processes in health and disease. Moreover, more specific treatments for ...fear-related disorders such as posttraumatic stress disorder and phobias may help to decrease their negative impact on mental health. In this line, the Tachykinin 2 (Tac2) pathway in the central amygdala (CeA) has been shown to be sufficient and necessary for the modulation of fear memory consolidation. CeA-Tac2 antagonism and its pharmacogenetic temporal inhibition impair fear memory in male mice. Surprisingly, we demonstrate here the opposite effect of Tac2 blockade on enhancing fear memory consolidation in females. Furthermore, we show that CeA-testosterone in males, CeA-estradiol in females and Akt/GSK3β/β-Catenin signaling both mediate the opposite-sex differential Tac2 pathway regulation of fear memory.
Exposure to traumatic stress can lead to fear dysregulation, which has been associated with posttraumatic stress disorder (PTSD). Previous work showed that a polymorphism in the PACAP-PAC1R ...(pituitary adenylate cyclase-activating polypeptide) system is associated with PTSD risk in women, and PACAP (ADCYAP1)-PAC1R (ADCYAP1R1) are highly expressed in the hypothalamus. Here, we show that female mice subjected to acute stress immobilization (IMO) have fear extinction impairments related to Adcyap1 and Adcyap1r1 mRNA upregulation in the hypothalamus, PACAP-c-Fos downregulation in the Medial Amygdala (MeA), and PACAP-FosB/ΔFosB upregulation in the Ventromedial Hypothalamus dorsomedial part (VMHdm). DREADD-mediated inhibition of MeA neurons projecting to the VMHdm during IMO rescues both PACAP upregulation in VMHdm and the fear extinction impairment. We also found that women with the risk genotype of ADCYAP1R1 rs2267735 polymorphism have impaired fear extinction.
•Female victims of sexual assault have a high predisposition to develop acute stress disorder.•Nationality, psychiatric history, peritraumatic dissociation and type of assault are risk factors ...associated to acute stress disorder.•The risk factors can be used in the emergency department to detect vulnerable victims that require early interventions.
Sexual assault is one of the most traumatic events a person can experience. Despite this, information regarding the risk factors associated with the development of Acute Stress Disorder (ASD) in sexual assault victims is scarce. A follow-up prospective cohort study was designed to examine the prevalence and risk factors of ASD in women exposed to a recent sexual assault. A total of 156 women were treated at the Emergency Department of a university general hospital shortly after sexual assault. Sociodemographic, clinical and sexual assault-related variables were collected. The Acute Stress Disorder Interview was used to estimate the prevalence of ASD at three weeks post-SA. From the 156 victims, 66.6% (N = 104) met ASD diagnosis using DSM-5 criteria, whereas 59.6% (N = 93) met ASD diagnosis using DSM-IV criteria. The risk factors associated with the development of ASD were nationality, psychiatric history, peritraumatic dissociation and type of assault. In conclusion, the prevalence of ASD in female victims of recent sexual assault was high, affecting approximately two thirds of them. The recognition of the risk factors associated with ASD development, like peritraumatic dissociation or type of assault, may aid in the prompt detection of vulnerable women that require early and specific interventions shortly after trauma.
Three experiments were conducted to evaluate the effect of in ovo administration of FloraMax®-B11 (FM) on Marek's disease (MD) herpesvirus of turkeys (HVT) vaccine protective efficacy, hatchability, ...microbiota composition, morphometric analysis, and Salmonella enteritidis (SE) infection in chickens. Experiment 1 consisted of 3 trials. In trials 1 and 2, d 18 White Leghorn 15I5x71 embryos were randomly distributed in 4 groups: 1) HVT vaccinated in ovo and no Marek's disease virus (MDV) challenge; 2), HVT + FM vaccinated in ovo and no MDV challenge; 3) HVT vaccinated in ovo and challenge with virulent MDV (vMDV; strain 583A); and 4), HVT + FM vaccinated in ovo and challenge with vMDV. Trial 3 was designed exactly the same as Experiment 1 but chicks were challenged with very virulent MDV (vvMDV; strains Md5 and 612). Birds were monitored until 8 wk of age, and tested for MD incidence. Experiment 2 consisted of 3 trials. In each trial, d 18 broiler embryos were injected in ovo with either saline or FM to measure hatchability and gastrointestinal bacterial composition. In Experiment 3, d 18 broiler embryos were injected in ovo with either saline or FM. All chickens that hatched were orally gavaged with SE at hatch and kept for 7 d to monitor post-hatch BW. No significant difference (P > 0.05) between MD percentage in birds vaccinated with HVT alone or HVT + FM were observed in Experiment 1. In Experiment 2, probiotic did not negatively affect hatchability, but did reduce lactose positive Gram-negative bacteria. Further, increase in BW was associated with higher villi surface area in the ileum in chickens that received the probiotic as well as a significant reduction in the SE incidence in Experiment 3. These results suggest that in ovo administration of FM does not negatively impact the ability of HVT to protect against MD or hatchability of chickens, but improves BW during the first 7 d of life and decreases SE recovery in chickens.
This work assesses the influence of different outdoor and operating conditions on the performance of an air-to-water CO2 heat pump for domestic hot water (DHW) generation. For that purpose, an air to ...water CO2 heat pump with internal heat exchanger (IHX) was developed and characterized in an experimental campaign under well-controlled lab conditions. The system includes an in-house control system implemented to operate at the optimal gas cooler pressure. The heat pump and the control system are tested for DHW generation. The heat pump uses a finned-tubes heat exchanger as evaporator and plate heat exchangers as gas cooler and internal heat exchanger. The numerical model used a 1dimensional, cell by cell discretization method to characterize the performance of both, the gas-cooler and the evaporator under a wide range of values of their key variables. The IHX is also modelled with the same strategy. ARHI equations are considered to describe the compressor performance. The experimental data obtained are used to validate a numerical model of the heat pump under different air velocities, air temperatures and air humidity at the evaporator. The effectiveness of the control system proposed is experimentally confirmed during the experimental tests. Results show a good agreement between the numerical simulations and the experimental data what permits to validate the model and to assess the performance of the transcritical heat pump under different climate conditions.
Increasing urbanization is likely to intensify the urban heat island effect, decrease outdoor thermal comfort, and enhance runoff generation in cities. Urban green spaces are often proposed as a ...mitigation strategy to counteract these adverse effects, and many recent developments of urban climate models focus on the inclusion of green and blue infrastructure to inform urban planning. However, many models still lack the ability to account for different plant types and oversimplify the interactions between the built environment, vegetation, and hydrology.
In this study, we present an urban ecohydrological model, Urban Tethys-Chloris (UT&C), that combines principles of ecosystem modelling with an urban canopy scheme accounting for the biophysical and ecophysiological characteristics of roof vegetation, ground vegetation, and urban trees. UT&C is a fully coupled energy and water balance model that calculates 2 m air temperature, 2 m humidity, and surface temperatures based on the infinite urban canyon approach. It further calculates the urban hydrological fluxes in the absence of snow, including transpiration as a function of plant photosynthesis. Hence, UT&C accounts for the effects of different plant types on the urban climate and hydrology, as well as the effects of the urban environment on plant well-being and performance.
UT&C performs well when compared against energy flux measurements of eddy-covariance towers located in three cities in different climates (Singapore, Melbourne, and Phoenix).
A sensitivity analysis, performed as a proof of concept for the city of Singapore, shows a mean decrease in 2 m air temperature of 1.1 ∘C for fully grass-covered ground, 0.2 ∘C for high values of leaf area index (LAI), and 0.3 ∘C for high values of Vc,max (an expression of photosynthetic capacity). These reductions in temperature were combined with a simultaneous increase in relative humidity by 6.5 %, 2.1 %, and 1.6 %, for fully grass-covered ground, high values of LAI, and high values of Vc,max, respectively. Furthermore, the increase of pervious vegetated ground is able to significantly reduce surface runoff.
Abstract We report the cloning and molecular characterization of the zfPDYN. The complete open reading frame for this propeptide is comprised in two exons that are localized on chromosome 23. zfPDYN ...cDNA codes for a polypeptide of 252 amino acids that contains the consensus sequences for four opioid peptides: an Ile-enkephalin, the neo-endorphins, dynorphin A and dynorphin B. Upon comparison between zebrafish (zfDYN A) and mammalian dynorphin A (mDYN A) it has been stated that these two peptides only differ in two amino acids: the Leu5 is replaced by Met5 and the Lys13 by Arg13 . Taking into consideration that mDYN A is able to bind to the three mammalian opioid receptors, we have compared the pharmacological profile of zfDYN A and mDYN A on the zebrafish opioid receptors. By means of radioligand binding techniques, we have established that these two dynorphins bind and activate all of the cloned opioid receptors from zebrafish (delta-, mu- and kappa-like), although with different affinities. zfDYN A and mDYN A displace 3 H-diprenorphine binding with Ki values on the nanomolar range, showing greater affinity for zebrafish opioid receptor (ZFOR) 3 (kappa) receptor. ZFOR1 (delta) and ZFOR4 (delta) present higher affinity for zfDYN A than for mDYN A, while the opposing behavior is observed in ZFOR2 (mu). Functional 35 Sguanosine 5′-γ-thiotriphosphate (GTPγS) stimulation experiments indicate that these two peptides fully activate the zebrafish opioid receptors, although the mean effective dose (EC50 ) values obtained for ZFOR2 and ZFOR3 receptors are lower than those seen for ZFOR1 and ZFOR4. A comparative study indicates that mammalian and zebrafish opioid receptors might bind their corresponding dynorphin A in a similar fashion, hence suggesting an important role of the opioid system through the vertebrate evolution.
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