Circuit-specific hippocampal ΔFosB underlies resilience to stress-induced social avoidance

Eagle, Andrew L.; Manning, Claire; Williams, Elizabeth; Bastle, Ryan M.; Gajewski, Paula A.; Garrison, Amber; Wirtz, Alexis J.; Akguen, Seda; Brandel-Ankrapp, Katie; Endege, Wilson O.; Boyce, Frederick M.; Ohnishi, Yoshinori N.; Mazei-Robison, Michelle S.; Maze, Ian; Neve, Rachel L.; Robison, Alfred J.

doi:10.1038/s41467-020-17825-x

Cited by 44 publications

(34 citation statements)

References 57 publications

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“…Psychosocial stressors lead to immune activation in both humans and laboratory animals, which contributes to the behavioral sequelae of stressful stimuli such as reductions in cognitive ability 56 and reduced sociability. 57–59 Social defeat models are widely used in the neurosciences 36 , 60–62 and, more recently, microbiome research. 63–65 And, while these models can involve wounding that contribute to immune and behavioral sequelae, 66–68 the current stressor was developed to limit defeat-associated wounds.…”

Section: Discussionmentioning

confidence: 99%

Stressor-Induced Reduction in Cognitive Behavior is Associated with Impaired Colonic Mucus Layer Integrity and is Dependent Upon the LPS-Binding Protein Receptor CD14

Jaggers

DiSabato

Loman

et al. 2022

JIR

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Purpose Commensal microbes are impacted by stressor exposure and are known contributors to cognitive and social behaviors, but the pathways through which gut microbes influence stressor-induced behavioral changes are mostly unknown. A murine social stressor was used to determine whether host–microbe interactions are necessary for stressor-induced inflammation, including neuroinflammation, that leads to reduced cognitive and social behavior. Methods C57BL/6 male mice were exposed to a paired fighting social stressor over a 1 hr period for 6 consecutive days. Y-maze and social interaction behaviors were tested following the last day of the stressor. Serum cytokines and lipopolysaccharide binding protein (LBP) were measured and the number and morphology of hippocampal microglia determined via immunohistochemistry. Intestinal mucous thickness and antimicrobial peptide expression were determined via fluorescent staining and real-time PCR (respectively) and microbial community composition was assessed using 16S rRNA gene amplicon sequencing. To determine whether the microbiota or the LBP receptor (CD14) are necessary for stressor-induced behavioral changes, experiments were performed in mice treated with a broad-spectrum antibiotic cocktail or in CD14 −/− mice. Results The stressor reduced Y-maze spontaneous alternations, which was accompanied by increased microglia in the hippocampus, increased circulating cytokines (eg, IL-6, TNF-α) and LBP, and reduced intestinal mucus thickness while increasing antimicrobial peptides and cytokines. These stressor-induced changes were largely prevented in mice given broad-spectrum antibiotics and in CD14 −/− mice. In contrast, social stressor-induced alterations of social behavior were not microbe-dependent. Conclusion Stressor-induced cognitive deficits involve enhanced bacterial interaction with the intestine, leading to low-grade, CD14-dependent, inflammation.

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Section: Discussionmentioning

confidence: 99%

Stressor-Induced Reduction in Cognitive Behavior is Associated with Impaired Colonic Mucus Layer Integrity and is Dependent Upon the LPS-Binding Protein Receptor CD14

Jaggers

DiSabato

Loman

et al. 2022

JIR

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“…Although numerous studies have focused on acute stimulation and cell type-specific control of the activity of vCA1 pyramidal neurons projecting from/to other brain areas with optogenetic approaches, less attention was paid to the dynamic molecular events in the vCA1 under chronic stress ( Eagle et al., 2020 ). We demonstrated a critical role of CaMKIIβ-mediated expression of AMPA receptor GluA1 in the PSD fraction of vCA1 pyramidal neurons in the behavioral response under stress.…”

Section: Discussionmentioning

confidence: 99%

Gene-environment interactions mediate stress susceptibility and resilience through the CaMKIIβ/TARPγ-8/AMPAR pathway

Sakai

Inaba

et al. 2021

iScience

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“…Compared to acute stress, chronic stress leads to the continuous release of neuroendocrine hormones (22)(23)(24), resulting in pathological changes (25)(26)(27). Chronic stress can increase the risk for the onset and progression of tumors because of its effects on the neuroendocrine system (28-30).…”

Section: Discussionmentioning

confidence: 99%

The central nervous system can directly regulate breast cancer progression and blockage by quercetin

Luo¹,

Zhang²,

Liu³

et al. 2021

Ann Transl Med

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Background: Neuroinflammation involving the central nervous system (CNS), such as depression, is associated with a significantly increased risk of cancer and cancer-specific mortality due to breast cancer. It is of great significance to learn about the regulatory process of CNS in breast cancer progression.Methods: We established a depressive MMTV-PyVT mouse model. The expression levels of neurotransmitters in the serum of depression animal models were assessed by enzyme-linked immunosorbent assay (ELISA). Changes of the microglia cells in the mice's brains were evaluated by immunofluorescence and reverse transcription-polymerase chain reaction (RT-PCR). Breast cancer progression was assessed by immunohistochemistry (IHC) analysis. To further investigate the mechanism by which ant-depressant drugs disrupt breast cancer progression, protein sequencing and network pharmacology were applied to identify related targets. Furthermore, we used conditioned medium from BV-2 microglia to culture breast cancer cells and treated the cells with quercetin at different concentrations; cell viability was assessed by the MTT assay.Results: Our results show a possible regulatory target between neuroinflammation in the CNS and development of breast cancer, along with the reversal effect of quercetin on breast cancer progression.Conclusions: Chronic stress may be an indicator of breast cancer and that quercetin could be an effective treatment for breast cancer patients with chronic stress.

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Circuit-specific hippocampal ΔFosB underlies resilience to stress-induced social avoidance

Cited by 44 publications

References 57 publications

Stressor-Induced Reduction in Cognitive Behavior is Associated with Impaired Colonic Mucus Layer Integrity and is Dependent Upon the LPS-Binding Protein Receptor CD14

Stressor-Induced Reduction in Cognitive Behavior is Associated with Impaired Colonic Mucus Layer Integrity and is Dependent Upon the LPS-Binding Protein Receptor CD14

Gene-environment interactions mediate stress susceptibility and resilience through the CaMKIIβ/TARPγ-8/AMPAR pathway

The central nervous system can directly regulate breast cancer progression and blockage by quercetin

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