scholarly journals Pubertal Androgens Reduce the Effects of Social Stress on Anxiety-related Behaviors in California Mice

2020 ◽  
Author(s):  
Emily C. Wright ◽  
Hannah I. Culkin ◽  
Shwetha Sekar ◽  
Amita Kapoor ◽  
Cody Corbett ◽  
...  

AbstractAdolescence is an important developmental period during which anxiety-related behaviors differentiate in males and females. In humans anxiety prevalence increases to a greater degree in women than men after puberty, but the mechanism is unknown. We used social defeat stress to model anxiety behaviors in California mouse, a species in which aggressive females allow for comparison of social anxiety behaviors across sex. Adult female California mice show reduced social approach and increased social vigilance after exposure to stress, while these changes are weaker in males. Here we show that in juveniles, social defeat reduces social approach and increases social vigilance in both males and females. Next, we show that prepubertal castration sensitizes adult males to social defeat. However, when pubertal castration was paired with either testosterone or dihydrostesterone replacement, effects of defeat on social approach and vigilance were blunted in adult males. We also showed that effects of defeat on social behavior in juveniles were oxytocin receptor dependent, as has been described for adult females. This work highlights the importance of pubertal testosterone to the development of sex differences in anxiety behavior, and provides evidence that androgen receptors play an important role in the development of neural circuits of anxiety.

2020 ◽  
Author(s):  
Natalia Duque-Wilckens ◽  
Lisette Y. Torres ◽  
Sae Yokoyama ◽  
Vanessa A. Minie ◽  
Amy M. Tran ◽  
...  

AbstractOxytocin increases the salience of both positive and negative social contexts and it is thought that these diverse actions on behavior are mediated in part through circuit-specific action. This hypothesis is based primarily on manipulations of oxytocin receptor function, leaving open the question of whether different populations of oxytocin neurons mediate different effects on behavior. Here we inhibited oxytocin synthesis in a social stress-sensitive population of oxytocin neurons specifically within the medioventral bed nucleus of the stria terminalis (BNSTmv). Oxytocin knock-down prevented stress-induced increases in social vigilance and decreases in social approach. Viral tracing of BNSTmv oxytocin neurons revealed fibers in regions controlling defensive behaviors including lateral hypothalamus, anterior hypothalamus, and anteromedial BNST (BNSTam). Oxytocin infusion into BNSTam in stress naïve mice increased social vigilance and reduced social approach. These results show that a population of extra-hypothalamic oxytocin neurons play a key role in controlling stress-induced social anxiety behaviors.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
F. Quessy ◽  
T. Bittar ◽  
L. J. Blanchette ◽  
M. Lévesque ◽  
B. Labonté

AbstractOur ability to develop the cognitive strategies required to deal with daily-life stress is regulated by region-specific neuronal networks. Experimental evidence suggests that prolonged stress in mice induces depressive-like behaviors via morphological, functional and molecular changes affecting the mesolimbic and mesocortical dopaminergic pathways. Yet, the molecular interactions underlying these changes are still poorly understood, and whether they affect males and females similarly is unknown. Here, we used chronic social defeat stress (CSDS) to induce depressive-like behaviors in male and female mice. Density of the mesolimbic and mesocortical projections was assessed via immuno-histochemistry combined with Sholl analysis along with the staining of activity-dependent markers pERK and c-fos in the ventral tegmental area (VTA), nucleus accumbens (NAc) and medial prefrontal cortex (mPFC). Our results show that social stress decreases the density of TH+ dopaminergic axonal projections in the deep layers of the mPFC in susceptible but not resilient male and female mice. Consistently, our analyses suggest that pERK expression is decreased in the mPFC but increased in the NAc following CSDS in males and females, with no change in c-fos expression in both sexes. Overall, our findings indicate that social defeat stress impacts the mesolimbic and mesocortical pathways by altering the molecular interactions regulating somatic and axonal plasticity in males and females.


2021 ◽  
Author(s):  
Francis Quessy ◽  
Thibault Bittar ◽  
Léa-Jeanne Blanchette ◽  
Martin Lévesque ◽  
Benoit Labonte

Abstract Our ability to develop the cognitive strategies required to deal with daily-life stress is regulated by region-specific neuronal networks. Experimental evidences suggest that prolonged stress in mice induces depressive-like behaviors via morphological, functional and molecular changes affecting the mesolimbic and mesocortical dopaminergic pathways. Yet, the molecular interactions underlying these changes are still poorly understood and whether they affect males and females similarly is unknown. Here, we used chronic social defeat stress (CSDS) to induce depressive-like behaviors in male and female mice. Density of the mesolimbic and cortical projections was assessed via immuno-histochemistry combined with Sholl analysis along with the staining of the activity-dependent markers pERK and c-Fos in the ventral tegmental area (VTA), nucleus accumbens (NAc) and medial prefrontal cortex (mPFC). We showed that social stress decreases the density of dopaminergic axonal projections to the mPFC but not to the NAc in susceptible and resilient mice. This was accompanied by sex-specific alterations of pERK and c-Fos expression in the VTA of susceptible but not resilient mice. Our results indicate that social defeat stress impacts the mesolimbic and mesocortical pathways by altering the molecular interactions regulating somatic and axonal plasticity differently in males and females.


2020 ◽  
Author(s):  
Deepika Patel ◽  
Ioannis Koutlas ◽  
Sebastiaan H. de Waard ◽  
Bauke Buwalda

ABSTRACTSuppression of hippocampal neurogenesis is a readout for stress-induced alterations in neuroplasticity. In this study, we hypothesized that a single episode of severe social or non-social stress would differentially suppress neurogenesis in the dentate gyrus (DG) 10 days later in two rat strains. We anticipated that the suppression following social stress would be less severe in wildtype Groningen (WTG) rats, a rat strain considered relatively resilient to social stressors. Male Wistar and WTG were subjected to either social defeat or to immobilization stress. Behavioral response to social defeat and acute corticosterone response to both stressors was measured as well as anxiety behavior 10 days later on the elevated plus maze. Subsequently, brains were collected following cardiac aldehyde perfusion. The behavioral freezing response to defeat was much stronger in Wistar rats as compared to WTG rats. Acute corticosteroid response was similar in both strains although Wistar rats more rapidly resumed baseline values. There was no significant effect of both stressors on hippocampal DG cell proliferation and differentiation as well as on anxiety behavior. However, a striking strain difference appeared in anxiety behavior and both markers of neurogenesis. The WTG strain exhibiting much lower anxiety as well as reduced rate of hippocampal neurogenesis under all treatments. The results in this study suggest that both short-lasting acute stressors failed to induce lasting anxiety or decreased neurogenesis in the DG. Future studies could explore if and how rate of hippocampal neurogenesis is related with behavioral coping with stress.


2021 ◽  
Author(s):  
F Quessy ◽  
T Bittar ◽  
LJ Blanchette ◽  
M Lévesque ◽  
B Labonté

AbstractOur ability to develop the cognitive strategies required to deal with daily-life stress is regulated by region-specific neuronal networks. Experimental evidences suggest that prolonged stress in mice induces depressive-like behaviors via morphological, functional and molecular changes affecting the mesolimbic and mesocortical dopaminergic pathways. Yet, the molecular interactions underlying these changes are still poorly understood and whether they affect males and females similarly is unknown. Here, we used chronic social defeat stress (CSDS) to induce depressive-like behaviors in male and female mice. Density of the mesolimbic and cortical projections was assessed via immuno-histochemistry combined with Sholl analysis along with the staining of the activity-dependent markers pERK and c-Fos in the ventral tegmental area (VTA), nucleus accumbens (NAc) and medial prefrontal cortex (mPFC). We showed that social stress decreases the density of dopaminergic axonal projections to the mPFC but not to the NAc in susceptible and resilient mice. This was accompanied by sex-specific alterations of pERK and c-Fos expression in the VTA of susceptible but not resilient mice. Our results indicate that social defeat stress impacts the mesolimbic and mesocortical pathways by altering the molecular interactions regulating somatic and axonal plasticity differently in males and females.


2021 ◽  
Author(s):  
Alisson Pinto de Almeida ◽  
Marcus Vinícius Chrysóstomo Baldo ◽  
Simone Cristina Motta

Abstract In nature, confrontations between conspecifics are recurrent and related, in general, to the lack of resources such as food and territory. In this sense, adequate defence against a conspecific aggressor is essential for the individual’s survival and the group integrity. However, repeated social defeat is a significant stressor, promoting several behavioural changes, including on social defence per se. But what would be the neural basis of these behavioural changes? To explore some hypotheses about this, we investigated the effects of repeated social stress on neural circuits underlying the motivated behaviour social defence in male mice. The hypothalamus is an essential centre of these circuits. Different hypothalamic structures receive information about the conspecific from the medial amygdala and the bed nucleus of the terminal stria. Furthermore, the hypothalamus can receive environmental information via the septo-hippocampal-hypothalamic circuit. Both information is processed by the dorsal premammillary nucleus (PMD) and the ventrolateral portion of the ventromedial nucleus of the hypothalamus, which communicate with the periaqueductal grey, an important downstream site for behavioural emission. During our analysis, we observed that animals re-exposed three times to the aggressor spent more time in passive defence during their last exposure than in their first one. These animals also present a smaller mobilization of areas related to the processing of conspecific cues. In contrast, we did not observe changes in the PMD mobilization. Therefore, our data indicate that the balance between the activity of circuits related to conspecific processing and the PMD determines the pattern of social defence behaviour. Changes in this balance may be the basis of the adaptations in social defence after repeated social defeat.


2020 ◽  
Vol 117 (42) ◽  
pp. 26406-26413 ◽  
Author(s):  
Natalia Duque-Wilckens ◽  
Lisette Y. Torres ◽  
Sae Yokoyama ◽  
Vanessa A. Minie ◽  
Amy M. Tran ◽  
...  

Oxytocin increases the salience of both positive and negative social contexts and it is thought that these diverse actions on behavior are mediated in part through circuit-specific action. This hypothesis is based primarily on manipulations of oxytocin receptor function, leaving open the question of whether different populations of oxytocin neurons mediate different effects on behavior. Here we inhibited oxytocin synthesis in a stress-sensitive population of oxytocin neurons specifically within the medioventral bed nucleus of the stria terminalis (BNSTmv). Oxytocin knockdown prevented social stress-induced increases in social vigilance and decreases in social approach. Viral tracing of BNSTmv oxytocin neurons revealed fibers in regions controlling defensive behaviors, including lateral hypothalamus, anterior hypothalamus, and anteromedial BNST (BNSTam). Oxytocin infusion into BNSTam in stress naïve mice increased social vigilance and reduced social approach. These results show that a population of extrahypothalamic oxytocin neurons plays a key role in controlling stress-induced social anxiety behaviors.


2019 ◽  
Vol 53 (4) ◽  
pp. 325-334
Author(s):  
V. N. Peskov ◽  
N. A. Petrenko ◽  
V. Yu. Reminnyi

Abstract We study size-at-age and sexual variability of morphometric characteristics of the marsh frog. According to the size of the body, males were divided into three size-age groups (juvenis, subadultus, adultus), females — into four groups (juvenis, subadultus, adultus, adultus-I). We found that the chronological age of frogs (skeletochronology) does not always correspond to their biological age (size and proportions of the body). We noted that the semi-adult males are reliably larger than females by mean values of 26 studied morphometric characters. Males and females of “adultus” group do not differ by linear body size, significant differences were found in body proportions (7 characters). For the females of “adultus-I” group, the mean values of 26 characters are significantly larger than for “adultus” males. The results of our study showed that with the age of the marsh frog, the level of exhibition, directionality and structure of morphometric sex differences changes.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Katherine A. Partrick ◽  
Anna M. Rosenhauer ◽  
Jérémie Auger ◽  
Amanda R. Arnold ◽  
Nicole M. Ronczkowski ◽  
...  

AbstractSocial stress exacerbates anxious and depressive behaviors in humans. Similarly, anxiety- and depressive-like behaviors are triggered by social stress in a variety of non-human animals. Here, we tested whether oral administration of the putative anxiolytic probiotic strains Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 reduces the striking increase in anxiety-like behavior and changes in gut microbiota observed following social defeat stress in Syrian hamsters. We administered the probiotic at two different doses for 21 days, and 16S rRNA gene amplicon sequencing revealed a shift in microbial structure following probiotic administration at both doses, independently of stress. Probiotic administration at either dose increased anti-inflammatory cytokines IL-4, IL-5, and IL-10 compared to placebo. Surprisingly, probiotic administration at the low dose, equivalent to the one used in humans, significantly increased social avoidance and decreased social interaction. This behavioral change was associated with a reduction in microbial richness in this group. Together, these results demonstrate that probiotic administration alters gut microbial composition and may promote an anti-inflammatory profile but that these changes may not promote reductions in behavioral responses to social stress.


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