Microglia activation is associated with IFN-α induced depressive-like behavior

Wachholz, Simone; Eßlinger, Manuela; Plümper, Jennifer; Manitz, Marie-Pierre; Juckel, Georg; Friebe, Astrid

doi:10.1016/j.bbi.2015.09.016

Cited by 70 publications

(48 citation statements)

References 67 publications

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“…This indicates that 1) there is a large therapeutic window to harness and desensitize the immune system of the CNS, and 2) the brain may be susceptible to systemic peripheral immune challenges following TBI. The link between microglial priming and depression is further supported by studies devoid of head trauma entirely where repeated injections of inflammatory cytokines induce depressive symptoms only after microglia become primed 66 .…”

Section: Immunological Perspectives Of Tbi Sequelaementioning

confidence: 67%

The bidirectional gut-brain-microbiota axis as a potential nexus between traumatic brain injury, inflammation, and disease

Sundman

Chen

Subbian

et al. 2017

Brain, Behavior, and Immunity

145

103

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The bidirectional gut-brain-microbiota axis as a potential nexus between traumatic brain injury, inflammation, and disease. AbstractAs head injuries and their sequelae have become an increasingly salient matter of public health, experts in the field have made great progress elucidating the biological processes occurring within the brain at the moment of injury and throughout the recovery thereafter. Given the extraordinary rate at which our collective knowledge of neurotrauma has grown, new insights may be revealed by examining the existing literature across disciplines with a new perspective. This article will aim to expand the scope of this rapidly evolving field of research beyond the confines of the central nervous system (CNS). Specifically, we will examine the extent to which the bidirectional influence of the gut-brain axis modulates the complex biological processes occurring at the time of traumatic brain injury (TBI) and over the days, months, and years that follow. In addition to local enteric signals originating in the gut, it is well accepted that gastrointestinal (GI) physiology is highly regulated by innervation from the CNS. Conversely, emerging data suggests that the function and health of the CNS is modulated by the interaction between 1) neurotransmitters, immune signaling, hormones, and neuropeptides produced in the gut, 2) the composition of the gut microbiota, and 3) integrity of the intestinal wall serving as a barrier to the external environment. Specific to TBI, existing pre-clinical data indicates that head injuries can cause structural and functional damage to the GI tract, but research directly investigating the neuronal consequences of this intestinal damage is lacking. Despite this void, the proposed mechanisms emanating from a damaged gut are closely implicated in the inflammatory processes known to promote neuropathology in the brain following TBI, which suggests the gut-brain axis may be a therapeutic target to reduce the risk of Chronic Traumatic Encephalopathy and other neurodegenerative diseases following TBI. To better appreciate how various peripheral influences are implicated in the health of the CNS following TBI, this paper will also review the secondary biological injury mechanisms and the dynamic pathophysiological response to neurotrauma. Together, this review article will attempt to connect the dots to reveal novel insights into the bidirectional influence of the gut-brain axis and propose a conceptual model relevant to the recovery from TBI and subsequent risk for future neurological conditions.

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Section: Immunological Perspectives Of Tbi Sequelaementioning

confidence: 67%

The bidirectional gut-brain-microbiota axis as a potential nexus between traumatic brain injury, inflammation, and disease

Sundman

Chen

Subbian

et al. 2017

Brain, Behavior, and Immunity

145

103

View full text Add to dashboard Cite

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“…Recent studies have shown that impairment of the normal structure and function of microglia, caused by autoimmune diseases, can result in depression and associated impairments in neuroplasticity and neurogenesis [19] and interferon-α-induced activation of microglia was particularly relevant to depressive-like behavior. [20] Additionally, a study in mice suggested that enriched environment-induced Adiponectin increase within the brain regulates microglia and brain macrophages phenotype and activation state, thus reducing neuroinflammation and depressive-like behaviors in mice. [21] …”

Section: Discussionmentioning

confidence: 99%

The impact of systemic lupus erythematosus on women's sexual functioning

Yin

Xu²,

Li³

et al. 2017

Medicine

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Background:A number of studies have reported the relationship between women's sexual problems and systemic lupus erythematosus (SLE). However, the results are contradictory. The objective of this paper was to explore the impact of SLE on women's sexual function.Methods:PubMed, Web of Science, CNKI Scholar, VIP and WanFang databases were searched up to April 2017. Studies evaluating the impact of SLE on women's sexual function with the use of Female Sexual Function Index (FSFI) scoring system were included. Statistical analyses were executed using version 5.0 Review Manager statistical software. Data were pooled using a fixed or random effects model according to heterogeneity.Results:A total of 2 identified studies matched the inclusion criteria, reporting on a total of 236 patients with SLE. No significant difference was observed between SLE patients and healthy controls on desire (P = .24; MD = −0.44 [−1.17, 0.29]), arousal (P = .12; MD = −0.39 [−0.89, 0.11]), lubrication (P = .17; MD = −0.53 [−1.28, 0.23]), orgasm (P = .27; MD = −0.27 [−0.75, 0.21]), satisfaction (P = .25; MD = −0.10 [−0.27, 0.07]) and pain (P = .17; MD = −0.50 [−1.22, 0.22]), except for total FSFI (P = .001; MD = −1.24 [−1.97, −0.50]).Conclusion:SLE has some influence on women’ sexual function. However, further studies of a larger population of female patients are required to further evaluate the mechanism by which SLE affects sexual function.

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“…IFN-α induces a systemic immune response associated with sickness behaviour, and, when administered over weeks or months as a treatment for patients with cancer or hepatitis C, is associated with a diagnosis of major depression in up to 30-50% of patients, and is thus considered the most validated clinical model of inflammation-induced depression 28 . Supporting our choice of using this model, preclinical studies have shown that peripheral IFN-α treatment in mice induces activation of microglia, and that this activation is associated with depressive-like behaviour 29,30 .…”

Section: Introductionmentioning

confidence: 99%

PET imaging shows no changes in TSPO brain density after IFN-α immune challenge in healthy human volunteers

et al. 2020

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Depression is associated with peripheral inflammation, but its link with brain microglial activity remains unclear. In seven healthy males, we used repeated translocator protein-Positron Emission Tomography (TSPO-PET) dynamic scans with [ 11 C]PBR28 to image brain microglial activation before and 24 h after the immune challenge interferon (IFN)-α. We also investigated the association between changes in peripheral inflammation, changes in microglial activity, and changes in mood. IFN-α administration decreased [ 11 C]PBR28 PET tissue volume of distribution (Vt) across the brain (−20 ± 4%; t 6 = 4.1, p = 0.01), but after correction for radioligand free-plasma fraction there were no longer any changes (+23 ± 31%; t = 0.1, p = 0.91). IFN-α increased serum IL-6 (1826 ± 513%, t 6 = −7.5, p < 0.001), IL-7 (39 ± 12%, t 6 = −3.6, p = 0.01), IL-10 (328 ± 48%, t 6 = −12.8, p < 0.001), and IFN-γ (272 ± 64%, t 6 = −7.0, p < 0.001) at 4-6 h, and increased serum TNF-α (49 ± 7.6%, t 6 = −7.5, p < 0.001), IL-8 (39 ± 12%, t 6 = −3.5, p = 0.013), and C-reactive protein (1320 ± 459%, t 6 = −7.2, p < 0.001) at 24 h. IFN-α induced temporary mood changes and sickness symptoms after 4-6 h, measured as an increase in POMS-2 total mood score, confusion and fatigue, and a decrease in vigor and friendliness (all p ≤ 0.04). No association was found between changes in peripheral inflammation and changes in PET or mood measures. Our work suggests that brain TSPO-PET signal is highly dependent of inflammation-induced changes in ligand binding to plasma proteins. This limits its usefulness as a sensitive marker of neuroinflammation and consequently, data interpretation. Thus, our results can be interpreted as showing either that [ 11 C]PBR28 is not sensitive enough under these conditions, or that there is simply no microglial activation in this model.

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Microglia activation is associated with IFN-α induced depressive-like behavior

Cited by 70 publications

References 67 publications

The bidirectional gut-brain-microbiota axis as a potential nexus between traumatic brain injury, inflammation, and disease

The bidirectional gut-brain-microbiota axis as a potential nexus between traumatic brain injury, inflammation, and disease

The impact of systemic lupus erythematosus on women's sexual functioning

PET imaging shows no changes in TSPO brain density after IFN-α immune challenge in healthy human volunteers

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