510 - EFFECT OF SLEEP DEPRIVATION ON SOCIAL RESILIENCE THROUGH ΔFOSB ACTIVATION

Introduction:Stress can have a variety of detrimental effects on humans. From depression and anxiety to schizophrenia, stress plays a factor in the development of these diseases through neurochemical changes in the brain and elevated levels of hormones. Among the geriatric population, decreased sleep levels are known to be a frequent issue; insomnia rates among the senior population are much higher in frequency compared to any other age group. Sleep deprivation also leads to major consequences in the brain and sleep disruption is linked to neuropsychological illness; however, the specific mechanisms involved in these effects are not understood. This study focuses on the resilient effects of ΔFosB, a protein known to mediate resilience to stress and the direct effect of sleep deprivation on ΔFosB expression in areas known to mediate resilience to social stress. We hypothesize that ΔFosB may be part of the mechanism through which sleep alters resilience to social stress.Methods:Mice were sleep-deprived for an eight-hour period for five days. After sleep deprivation they were subject to social defeat and underwent avoidance testing. The brains of these mice were removed, and immunohistochemistry analysis was conducted to determine ∆FosB expression in various sections of the brain.Results:The preliminary findings of this study indicates that sleep is altered in resilient animals and that sleep deprivation may lead to increased resilience to social defeat. The most significant decrease in ∆FosB expression was found in the prelimbic cortex, a change associated with resilience, and which was observed after chronic sleep deprivation. Contrarily, there was also an increase of ∆FosB expression in the nucleus accumbens.Conclusion:These findings indicate that changes in ∆FosB activation in the brain is a significant factor for promoting resilient behavior in situations of social stress. In particular, a decrease in ∆FosB activation in the PLC plays a role in explaining how sleep deprivation contributes to decreased social resilience in situations of social stress.

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0429 Chronic Sleep Disturbance Causes Cognitive Impairment and Alzheimer’S Disease-Like Neuropathology

SLEEP ◽

10.1093/sleep/zsaa056.426 ◽

2020 ◽

Vol 43 (Supplement_1) ◽

pp. A164-A164

Author(s):

W Le

Keyword(s):

Cognitive Impairment ◽

Sleep Deprivation ◽

Sleep Disturbance ◽

Neuronal Apoptosis ◽

Senile Plaques ◽

Clinical Problem ◽

Geriatric Population ◽

Dementia Risk ◽

Neuropsychological Functions ◽

Chronic Sleep

Abstract Introduction Sleep disturbance is among the most common clinical problem and possesses a significant concern for the geriatric population. Recently, increasing evidence has indicated that disturbed sleep may not only affect neuropsychological functions, but also contribute to the cognitive impairment and, therefore, significantly increase dementia risk. Methods In the present study, we examined the potential impacts of chronic sleep deprivation (SD) on learning-memory and AD-related pathologies in AβPPswe/PS1ΔE9 transgenic (TG) mice and their wild-type (WT) littermates. Results Our results indicated that mice (both TG and WT) exposed to 2-month SD showed an altered amyloid-βprotein precursor processing, elevated level of phosphorylated tau protein, and impaired cognitive performance as compared to non-sleep deprivation (NSD) controls. Moreover, the SD-treated TG mice exhibited more amyloid-β1-42 production and developed more senile plaques in the cortex and hippocampus than NSD-treated TG mice. In addition, SD caused a striking neuronal mitochondrial damage, caspase cascade activation, and neuronal apoptosis in the hippocampus of both TG and WT mice. More importantly, all these behavioral, neuropathological, and biochemical changes induced by chronic SD were long lasting and were irreversible during a 3-month normal housing condition. Conclusion Collectively, these results indicate that chronic SD impairs learning and memory, exacerbates AD pathologies, and aggravates the mitochondria-mediated neuronal apoptosis in a long-lasting manner. Support Our findings provide important experimental evidence to prove that chronic sleep disturbance is a risk factor for AD.

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Toward Understanding the Sex Differences in the Biological Mechanism of Social Stress in Mouse Models

Frontiers in Psychiatry ◽

10.3389/fpsyt.2021.644161 ◽

2021 ◽

Vol 12 ◽

Author(s):

Aki Takahashi

Keyword(s):

Sex Differences ◽

Social Stress ◽

Social Defeat ◽

Preclinical Studies ◽

Biological Mechanism ◽

Depression And Anxiety ◽

Social Defeat Stress ◽

Pharmacological Interventions ◽

Recent Developments ◽

Stress Models

Significant sex differences in terms of prevalence, symptomatic profiles, severity, and comorbidities of psychiatric disorders are quite common. Women have been shown to be more vulnerable to stress and are nearly twice as likely as men to develop stress-related disorders such as depression and anxiety. Therefore, understanding sex differences with respect to the neurobiological mechanisms underlying stress-related disorders is important for developing more efficient pharmacological interventions for women. However, most preclinical studies on stress-related disorders have focused heavily on male rodents. Here, recent developments in the study of repeated social defeat stress models in female mice are summarized. Our findings suggest that a variety of factors need to be considered when employing this model.

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Blockade of D3 receptor prevents changes in DAT and D3R expression in the mesolimbic dopaminergic circuit produced by social stress- and cocaine prime-induced reinstatement of cocaine-CPP

Journal of Psychopharmacology ◽

10.1177/0269881120936468 ◽

2020 ◽

Vol 34 (11) ◽

pp. 1300-1315

Author(s):

Rocío Guerrero-Bautista ◽

Aurelio Franco-García ◽

Juana M Hidalgo ◽

Francisco Fernández-Gómez ◽

M Victoria Milanés ◽

...

Keyword(s):

Social Stress ◽

Social Defeat ◽

Behavioral Effects ◽

The Other ◽

D3 Receptor ◽

Male Mice ◽

Social Defeat Stress ◽

Priming Dose ◽

The Impact ◽

The Brain

Background: Cocaine may cause persistent changes in the brain, which are more apparent in DA transporter (DAT) and DA receptor availability within the nucleus accumbens (NAc). On the other hand, the DA D3 receptor (D3R) has emerged as a promising pharmacotherapeutic target for substance use disorders. Aims: This study aims to assess the impact of selective D3R antagonism on DAT and D3R after reinstatement of cocaine preference (CPP) induced by an acute session of social defeat stress (SDS) and a cocaine prime in mice after a period of abstinence. Methods: Male mice were conditioned with 25 mg/kg of cocaine for 4 days. After 60 days of extinction training mice were pretreated with the selective D3R antagonist SB-277011A before the re-exposure to a priming dose of cocaine or to a single SDS session. CPP scores were determined and levels of DAT, D3R, phospho Akt (pAkt) and phospho mTOR (pmTOR) were assessed in the NAc shell. Results: An increase in DAT and D3R expression was seen in the NAc after both a cocaine prime- and SDS-induced reinstatement of CPP. Pretreatment with SB-277011A blocked elevated DAT and D3R expression as well as SDS-induced reinstatement. By contrast, the blockade of D3R did not modified the cocaine prime-induced CPP. Changes in DAT and D3R expression do not seem to occur via the canonic pathway involving Akt/mTOR. Conclusions: Our results suggest that the selective D3R antagonist ability to inhibit DAT and D3R up-regulation could represent a possible mechanism for its behavioral effects in cocaine-memories reinstatement induced by social stress.

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Stress-induced sleep-like inactivity modulates stress susceptibility in mice

Scientific Reports ◽

10.1038/s41598-020-76717-8 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Midori Nagai ◽

Hirotaka Nagai ◽

Chisato Numa ◽

Tomoyuki Furuyashiki

Keyword(s):

Sleep Deprivation ◽

Social Stress ◽

Social Interest ◽

Social Behaviors ◽

Social Defeat ◽

Brain Regions ◽

Social Characteristics ◽

Social Avoidance ◽

Social Defeat Stress ◽

Positive Valence

AbstractSevere environmental and social stress induces dysregulation of sleep along with mood and cognitive disturbances. However, the role and mechanism of this sleep dysregulation remain elusive. Here we evaluated sleep-like inactivity measured by voluntary movements and its relationship to social behaviors in mice without or with social defeat stress as well as the stressed mice with subsequent sleep deprivation. Social defeat stress immediately induced sleep-like inactivity with decreased body temperature. In the social interaction test, the control mice showed high social interest and its correlation with social sniffing intensity, the latter of which indicates positive valence of social sniffing. After the stress, these social characteristics were maintained in stress-resilient mice, but disrupted in stress-susceptible mice, leading to social avoidance. Sleep deprivation after the stress decreased social sniffing intensity along with reduced social interest, but enhanced the exploratory activity with the positive valence of social sniffing. We also found by c-Fos immunohistochemistry that the stress activated sleep-related brain regions, the dorsomedial hypothalamus and ventrolateral periaqueductal gray. Collectively, these findings show that stress activates sleep-related brain regions and induces sleep-like inactivity, contributing to multiple roles of stress-induced sleep for social behaviors.

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Social defeat protocol and relevant biomarkers, implications for stress response physiology, drug abuse, mood disorders and individual stress vulnerability: a systematic review of the last decade

Trends in Psychiatry and Psychotherapy ◽

10.1590/2237-6089-2014-0034 ◽

2015 ◽

Vol 37 (2) ◽

pp. 51-66 ◽

Cited By ~ 31

Author(s):

Mailton Vasconcelos ◽

Dirson João Stein ◽

Rosa Maria M. de Almeida

Keyword(s):

Systematic Review ◽

Stress Response ◽

Social Defeat ◽

Stress Adaptation ◽

Addictive Behaviors ◽

Depression And Anxiety ◽

Stress Effects ◽

Stress Vulnerability ◽

Search Terms ◽

The Brain

Introduction: Social defeat (SD) in rats, which results from male intraspecific confrontations, is ethologically relevant and useful to understand stress effects on physiology and behavior.Methods: A systematic review of studies about biomarkers induced by the SD protocol and published from 2002 to 2013 was carried out in the electronic databases PubMed, Web of Knowledge and ScienceDirect. The search terms were: social defeat, rat, neurotrophins, neuroinflammatory markers, and transcriptional factors.Results: Classical and recently discovered biomarkers were found to be relevant in stress-induced states. Findings were summarized in accordance to the length of exposure to stress: single, repeated, intermittent and continuous SD. This review found that the brain-derived neurotrophic factor (BDNF) is a distinct marker of stress adaptation. Along with glucocorticoids and catecholamines, BDNF seems to be important in understanding stress physiology.Conclusion: The SD model provides a relevant tool to study stress response features, development of addictive behaviors, clinic depression and anxiety, as well as individual differences in vulnerability and resilience to stress.

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Sex-specific retinal anomalies induced by chronic social stress in mice

10.1101/2020.09.28.317230 ◽

2020 ◽

Author(s):

E Arsenault ◽

AA Lavigne ◽

S Mansouri ◽

K Francis ◽

TP Bittar ◽

...

Keyword(s):

Stress Response ◽

Social Stress ◽

Social Defeat ◽

Major Depressive ◽

Male And Female ◽

Retinal Activity ◽

Female Mice ◽

Chronic Social Defeat Stress ◽

Before And After ◽

The Brain

AbstractMajor depressive disorder (MDD) is one of the most common consequences of chronic stress. Still, there is currently no reliable biomarker to detect individuals at risk to develop MDD. Recently, the retina emerged as an effective way to approach the brain and investigate psychiatric disorders with the use of the electroretinogram (ERG). In this study, cones and rods ERGs were performed in male and female mice before and after chronic social defeat stress (CSDS). Mice were then divided as susceptible or resilient to stress. Significant results were only observed in rods ERGs. In males, susceptible mice showed prolonged a-wave implicit times at baseline that were shortened after CSDS. The a-wave was also decreased in both susceptible and resilient male mice after CSDS. In females, rod a-waves were shorter in susceptible than in control mice after CSDS resulting from the latter demonstrating delayed a-waves. Baseline ERGs were able to predict – to some extent – the expression of susceptibility and resilience before stress exposition in male and female mice. Overall, our findings suggest that retinal activity is a presumptive biomarker of stress response and that the ERG could potentially serve as a predicting tool of the stress response in mice.

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Ingestion of probiotic (Lactobacillus helveticus and Bifidobacterium longum) alters intestinal microbial structure and behavioral expression following social defeat stress

Scientific Reports ◽

10.1038/s41598-021-83284-z ◽

2021 ◽

Vol 11 (1) ◽

Cited By ~ 2

Author(s):

Katherine A. Partrick ◽

Anna M. Rosenhauer ◽

Jérémie Auger ◽

Amanda R. Arnold ◽

Nicole M. Ronczkowski ◽

...

Keyword(s):

Social Stress ◽

Bifidobacterium Longum ◽

Social Defeat ◽

Lactobacillus Helveticus ◽

Rrna Gene ◽

Social Avoidance ◽

Social Defeat Stress ◽

Microbial Structure ◽

Microbial Composition ◽

Anti Inflammatory

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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Residual, differential neurobehavioral deficits linger after multiple recovery nights following chronic sleep restriction or acute total sleep deprivation

SLEEP ◽

10.1093/sleep/zsaa224 ◽

2020 ◽

Author(s):

Erika M Yamazaki ◽

Caroline A Antler ◽

Charlotte R Lasek ◽

Namni Goel

Keyword(s):

Sleep Deprivation ◽

Response Speed ◽

Sleep Loss ◽

Sleep Restriction ◽

Total Sleep Deprivation ◽

Psychomotor Vigilance Test ◽

Recovery Sleep ◽

Time In Bed ◽

Neurobehavioral Deficits ◽

Chronic Sleep

Abstract Study Objectives The amount of recovery sleep needed to fully restore well-established neurobehavioral deficits from sleep loss remains unknown, as does whether the recovery pattern differs across measures after total sleep deprivation (TSD) and chronic sleep restriction (SR). Methods In total, 83 adults received two baseline nights (10–12-hour time in bed [TIB]) followed by five 4-hour TIB SR nights or 36-hour TSD and four recovery nights (R1–R4; 12-hour TIB). Neurobehavioral tests were completed every 2 hours during wakefulness and a Maintenance of Wakefulness Test measured physiological sleepiness. Polysomnography was collected on B2, R1, and R4 nights. Results TSD and SR produced significant deficits in cognitive performance, increases in self-reported sleepiness and fatigue, decreases in vigor, and increases in physiological sleepiness. Neurobehavioral recovery from SR occurred after R1 and was maintained for all measures except Psychomotor Vigilance Test (PVT) lapses and response speed, which failed to completely recover. Neurobehavioral recovery from TSD occurred after R1 and was maintained for all cognitive and self-reported measures, except for vigor. After TSD and SR, R1 recovery sleep was longer and of higher efficiency and better quality than R4 recovery sleep. Conclusions PVT impairments from SR failed to reverse completely; by contrast, vigor did not recover after TSD; all other deficits were reversed after sleep loss. These results suggest that TSD and SR induce sustained, differential biological, physiological, and/or neural changes, which remarkably are not reversed with chronic, long-duration recovery sleep. Our findings have critical implications for the population at large and for military and health professionals.

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