Neuroendocrine stress reactivity of male C57BL/6N mice following chronic oral corticosterone exposure during adulthood or adolescence

Shahanoor, Ziasmin; Sultana, Razia; Baker, Madelyn R.; Romeo, Russell D.

doi:10.1016/j.psyneuen.2017.10.001

Cited by 20 publications

(17 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although our in vitro recordings demonstrate a decrease in intrinsic excitability of CRH PVN neurons, previous work using cFOS as a proxy measure of excitability, in vivo, suggest these neurons remain responsive to stress, even during prolonged periods of CORT feedback 10 . To better understand the effect of persistent CORT feedback on CRH PVN neuron activity, we used in vivo fiber photometry to assess GCaMP6s activity in live, freely behaving mice.…”

Section: Validation Of Fiber Photometry For Repeated Recordings In Vivocontrasting

confidence: 83%

“…This is the first demonstration that neural networks responsive to hormonal feedback leverage adaptive mechanisms to overcome feedback. Previous studies show acute CORT feedback decreases activity in vivo 4 , yet cFOS studies suggest that activity is maintained after chronic feedback 10 . Our results provide stronger evidence that activity is maintained in vivo, and provide a synaptic mechanism that allows these neurons to overcome feedback.…”

Section: Discussionmentioning

confidence: 87%

“…Although persistent elevations in CORT are prevalent in large clinical cohorts, we understand very little about the consequences for neural stress circuits. This is highlighted by observations that although chronic CORT administration blunts the acute hormone response to stress 9 , it does not alter the reactivity of CRH PVN neurons to acute stress 10 .…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Adaptive synaptic plasticity maintains CRH neuron output during chronic glucocorticoid exposure

Rasiah

Rosenegger

Abant

et al. 2020

Preprint

View full text Add to dashboard Cite

An increase in circulating glucocorticoids (CORT) is an essential part of the response to stress. Sustained elevations of CORT, however, have dramatic consequences on behavior, endocrine systems and peripheral organs. Critically, they dampen the endocrine response to acute challenges and decrease intrinsic excitability of corticotropin-releasing hormone neurons in the paraventricular nucleus (CRH PVN ), suggesting key circuits may be less responsive to stress. Here, we make the surprising discovery that CRH PVN neurons harness a form of adaptive synaptic scaling to escape the persistent negative feedback pressure from CORT and maintain stable output in vivo. Specifically, there is an increase in glutamatergic drive to these cells that is mediated by a postsynaptic, multiplicative increase in synaptic strength. These findings suggest that dysfunctions associated with chronic stress may not be due to the primary actions of CORT, but instead reflect the emergence of synaptic adaptations as networks seek to re-establish intrinsic activity setpoints.

show abstract

Section: Validation Of Fiber Photometry For Repeated Recordings In Vivocontrasting

confidence: 83%

Section: Discussionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Adaptive synaptic plasticity maintains CRH neuron output during chronic glucocorticoid exposure

Rasiah

Rosenegger

Abant

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…More recently, one study reported that a slight modification to the chronic social instability protocol (every 3 days for 7 weeks) was effective for inducing pro-anxiety and depressive-like behaviours in adult male mice 40 , so intergenerational modifications could be further investigated in that model. While it is unknown whether different intergenerational outcomes are dependent on the age at which CORT treatment commences (juvenile vs adult), such a comparison would be challenging due to the established differences in the physical adaptative responses to chronic low-dose CORT treatment by adolescent (4 weeks of age) and adult (10 weeks of age) mice 29 . Any intergenerational effects observed would be confounded by secondary effects on the physical and sexual maturation of adolescent animals.…”

Section: Discussionmentioning

confidence: 99%

Limitations to intergenerational inheritance: subchronic paternal stress preconception does not influence offspring anxiety

Fennell

Busby

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Independent studies have observed that a paternal history of stress or trauma is associated with his children having a greater likelihood of developing psychopathologies such as anxiety disorders. This father-to-child effect is reproduced in several mouse models of stress, which have been crucial in developing a greater understanding of intergenerational epigenetic inheritance. We previously reported that treatment of C57Bl/6J male breeders with low-dose corticosterone (CORT) for 28 days prior to mating yielded increased anxiety-related behaviours in their male F1 offspring. The present study aimed to determine whether subchronic 7-day CORT treatment of male mice just prior to mating would be sufficient to induce intergenerational modifications of anxiety-related behaviours in offspring. We report that subchronic CORT treatment of male breeders reduced their week-on-week body weight gain and altered NR3C1 and CRH gene expression in the hypothalamus. There were no effects on sperm count and glucocorticoid receptor protein levels within the epididymal tissue of male breeders. Regarding the F1 offspring, screening for anxiety-related behaviours using the elevated-plus maze, light–dark box, and novelty-suppressed feeding test revealed no differences between the offspring of CORT-treated breeders compared to controls. Thus, it is crucial that future studies take into consideration the duration of exposure when assessing the intergenerational impacts of paternal health.

show abstract

“…Prolonged corticosterone (CORT) administration in rodents is a well-established model to mimic the physiological parameters of chronic stress and disrupt the HPA axis (Buret and van den Buuse, 2014 ; Shahanoor et al, 2017 ). The hypothalamic pituitary adrenal (HPA) axis is the well-conserved control center for the body's stress response.…”

Section: Introductionmentioning

confidence: 99%

Sex-Dependent Effects of Environmental Enrichment on Spatial Memory and Brain-Derived Neurotrophic Factor (BDNF) Signaling in a Developmental “Two-Hit” Mouse Model Combining BDNF Haploinsufficiency and Chronic Glucocorticoid Stimulation

Grech

Ratnayake

Hannan

et al. 2018

Front. Behav. Neurosci.

View full text Add to dashboard Cite

Neurodevelopmental disorders are thought to be caused by a combination of adverse genetic and environmental insults. The “two-hit” hypothesis suggests that an early first “hit” primes the developing brain to be vulnerable to a second “hit” during adolescence which triggers behavioral dysfunction. We have previously modeled this scenario in mice and found that the combined effect of a genetic hapolinsuffuciency in the brain-derived neurotrophic factor (BDNF) gene (1st hit) and chronic corticosterone (CORT) treatment during adolescence (2nd hit), caused spatial memory impairments in adulthood. Environmental enrichment (EE) protocols are designed to stimulate experience-dependent plasticity and have shown therapeutic actions. This study investigated whether EE can reverse these spatial memory impairments. Wild-type (WT) and BDNF heterozygous (HET) mice were treated with corticosterone (CORT) in their drinking water (50 mg/L) from weeks 6 to 8 and exposed to EE from 7 to 9 weeks. Enriched housing included open top cages with additional toys, tunnels, housing, and platforms. Y-maze novel preference testing, to assess short-term spatial memory, was performed at 10 weeks of age. At week 16 dorsal hippocampus tissue was obtained for Western blot analysis of expression levels of BDNF, the BDNF receptor TrkB, and NMDA receptor subunits, GluNR1, 2A and 2B. As in our previous studies, spatial memory was impaired in our two-hit (BDNF HET + CORT) mice. Simultaneous EE prevented these impairments. However, EE appeared to worsen spatial memory performance in WT mice, particularly those exposed to CORT. While BDNF levels were lower in BDNF HET mice as expected, there were no further effects of CORT or EE in males but a close to significant female CORT × EE × genotype interaction which qualitatively corresponded with Y-maze performance. However, EE caused both sex- and genotype-specific effects on phosphorylated TrkB residues and GluNR expression within the dorsal hippocampus, with GluNR2B levels in males changing in parallel with spatial memory performance. In conclusion, beneficial effects of EE on spatial memory emerge only following two developmental disruptions. The mechanisms by which EE exerts its effects are likely via regulation of multiple activity-dependent pathways, including TrkB and NMDA receptor signaling.

show abstract

Neuroendocrine stress reactivity of male C57BL/6N mice following chronic oral corticosterone exposure during adulthood or adolescence

Cited by 20 publications

References 29 publications

Adaptive synaptic plasticity maintains CRH neuron output during chronic glucocorticoid exposure

Adaptive synaptic plasticity maintains CRH neuron output during chronic glucocorticoid exposure

Limitations to intergenerational inheritance: subchronic paternal stress preconception does not influence offspring anxiety

Sex-Dependent Effects of Environmental Enrichment on Spatial Memory and Brain-Derived Neurotrophic Factor (BDNF) Signaling in a Developmental “Two-Hit” Mouse Model Combining BDNF Haploinsufficiency and Chronic Glucocorticoid Stimulation

Contact Info

Product

Resources

About