Neuroimmune Signaling: Cytokines and the CNS

Kennedy, Rachel H.; Silver, Rae

doi:10.1007/978-1-4614-6434-1_174-1

Cited by 37 publications

(30 citation statements)

References 32 publications

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“…The epithelial barrier disruption exposes the lungs or other tissues to bacterial infection. Pathophysiological mechanisms associated with COVID-19 induced cytokine storms are shown in Figure 1 (11,(43)(44)(45)(46)(47)(48)(49)(50).…”

Section: Significance Of Cytokine Stormmentioning

confidence: 99%

“…We propose that the immune system cytokine network may also communicate with the central nervous system (CNS) cytokine network, especially when the blood-brain-barrier (BBB) is compromised. Microglia and IL-1 activation can cause increased reactive oxygen species (ROS) production, phagocytosis, apoptosis, and increased cytokine expression (see Figure 2 ) within the CNS ( 43 ), leading to neural tissue damage through neuroinflammation, increased oxidative stress and excitotoxicity, and dysfunction in synaptic pruning. The systemic immune system cytokine network and the CNS cytokine network influence each other through the neuropeptidergic pathway involving neurokinin C and B, neuroendocrine peptides (NPY)/gastrin-releasing peptide (GRP), SPA-GRP {SPA: [(D-Arg, D-Trp, Leu)Substance P], a derivative of substance P}, and vasoactive intestinal polypeptide (VIP).…”

Section: Covid-19 and Cytokine Stormmentioning

confidence: 99%

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Cytokine Storm in COVID-19—Immunopathological Mechanisms, Clinical Considerations, and Therapeutic Approaches: The REPROGRAM Consortium Position Paper

et al. 2020

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† The COVID19 pandemic is causing an unprecedented public health crisis impacting healthcare systems, healthcare workers, and communities. The COVID-19 Pandemic Health System REsilience PROGRAM (REPROGRAM) consortium is an international not-for-profit think-tank for global pandemic preparedness and action Specialty section: This article was submitted to Multiple Sclerosis and Neuroimmunology, a section of the journal Frontiers in Immunology

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Section: Significance Of Cytokine Stormmentioning

confidence: 99%

Section: Covid-19 and Cytokine Stormmentioning

confidence: 99%

Cytokine Storm in COVID-19—Immunopathological Mechanisms, Clinical Considerations, and Therapeutic Approaches: The REPROGRAM Consortium Position Paper

et al. 2020

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“…The rationale behind the inflammatory/immune hypothesis derives from the involvement of immune systems in the physiological stress-sensing pathways and its interaction with HPA axis, autonomic nervous system (ANS), and central nervous system (CNS) by a mutual regulation. Animal models of depression revealed how the cytokines, once transported through the blood brain barrier by specific endothelial cell transporter or diffusing through deficient barrier areas, can directly or indirectly affect brain circuits, behaviors, and mood, acting on neurons, astrocytes, and microglia (Kennedy and Silver, 2016;Ambrée et al, 2018). Furthermore, inflammatory signals can converge on CNS through the vagus nerve or by means of infiltrating peripheral immune cells.…”

Section: Introductionmentioning

confidence: 99%

The Emerging Role of SGK1 (Serum- and Glucocorticoid-Regulated Kinase 1) in Major Depressive Disorder: Hypothesis and Mechanisms

et al. 2020

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Major depressive disorder (MDD) is a heterogeneous psychiatric disease characterized by persistent low mood, diminished interests, and impaired cognitive and social functions. The multifactorial etiology of MDD is still largely unknown because of the complex genetic and environmental interactions involved. Therefore, no established mechanism can explain all the aspects of the disease. In this light, an extensive research about the pathophysiology of MDD has been carried out. Several pathogenic hypotheses, such as monoamines deficiency and neurobiological alterations in the stress-responsive system, including the hypothalamic-pituitary-adrenal (HPA) axis and the immune system, have been proposed for MDD. Over time, remarkable studies, mainly on preclinical rodent models, linked the serum-and glucocorticoid-regulated kinase 1 (SGK1) to the main features of MDD. SGK1 is a serine/threonine kinase belonging to the AGK Kinase family. SGK1 is ubiquitously expressed, which plays a pivotal role in the hormonal regulation of several ion channels, carriers, pumps, and transcription factors or regulators. SGK1 expression is modulated by cell stress and hormones, including gluco-and mineralocorticoids. Compelling evidence suggests that increased SGK1 expression or function is related to the pathogenic stress hypothesis of major depression. Therefore, the first part of the present review highlights the putative role of SGK1 as a critical mediator in the dysregulation of the HPA axis, observed under chronic stress conditions, and its controversial role in the neuroinflammation as well. The second part depicts the negative regulation exerted by SGK1 in the expression of both the brain-derived neurotrophic factor (BDNF) and the vascular endothelial growth factor (VEGF), resulting in an anti-neurogenic activity. Finally, the review focuses on the antidepressant-like effects of anti-oxidative nutraceuticals in several preclinical model of depression, resulting from the restoration of the physiological expression and/or activity of SGK1, which leads to an increase in neurogenesis. In summary, the purpose of this review is a systematic analysis of literature depicting SGK1 as molecular junction of the complex mechanisms underlying the MDD in an effort to suggest the kinase as a potential biomarker and strategic target in modern molecular antidepressant therapy.

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“…In healthy individuals, CNS macrophages and microglia act as the primary immune response within the CNS, communicating with neurons by releasing a variety of cytokines and neurotrophic factors important to neuronal health and function [84-87]. Infection of these cells dysregulates production and release of inflammatory cytokines and neurotoxic viral proteins, activating neighboring uninfected cells and inducing further production of factors that perpetuate the neuroinflammatory environment.…”

Section: Hiv Neuropathogenesis In the Cart Eramentioning

confidence: 99%

The role of catecholamines in HIV neuropathogenesis

Nolan

Gaskill

2019

Brain Research

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The success of anti-retroviral therapy has improved the quality of life and lifespan of HIV + individuals, transforming HIV infection into a chronic condition. These improvements have come with a cost, as chronic HIV infection and long-term therapy have resulted in the emergence of a number of new pathologies. This includes a variety of the neuropathological and neurocognitive effects collectively known as HIVassociated neurocognitive disorders (HAND) or NeuroHIV. These effects persist even in the absence of viral replication, suggesting that they are mediated the long-term changes in the CNS induced by HIV infection rather than by active replication. Among these effects are significant changes in catecholaminergic neurotransmission, especially in dopaminergic brain regions. In HIV-infected individuals not treated with ARV show prominent neuropathology is common in dopamine-rich brain regions and altered autonomic nervous system activity. Even infected individuals on therapy, there is significant dopaminergic neuropathology, and elevated stress and norepinephrine levels correlate with a decreased effectiveness of antiretroviral drugs. As catecholamines function as immunomodulatory factors, the resultant dysregulation of catecholaminergic tone could substantially alter the development of HIVassociated neuroinflammation and neuropathology. In this review, we discuss the role of catecholamines in the etiology of HIV neuropathogenesis. Providing a comprehensive examination of what is known about these molecules in the context of HIV-associated disease demonstrates the importance of further studies in this area, and may open the door to new therapeutic strategies that specifically ameliorate the effects of catecholaminergic dysregulation on NeuroHIV.

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Neuroimmune Signaling: Cytokines and the CNS

Cited by 37 publications

References 32 publications

Cytokine Storm in COVID-19—Immunopathological Mechanisms, Clinical Considerations, and Therapeutic Approaches: The REPROGRAM Consortium Position Paper

Cytokine Storm in COVID-19—Immunopathological Mechanisms, Clinical Considerations, and Therapeutic Approaches: The REPROGRAM Consortium Position Paper

The Emerging Role of SGK1 (Serum- and Glucocorticoid-Regulated Kinase 1) in Major Depressive Disorder: Hypothesis and Mechanisms

The role of catecholamines in HIV neuropathogenesis

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