Hodgson, D

Sominsky, L

Walker, A

Frontiers in Neuroscience

PubMed

Luba Sominsky

Adam K. Walker

Deborah M. Hodgson

Frontiers - Publisher Connector

Editorial: Neuroinflammation and behavior

RMIT Research Repository

Neuroinflammation and behaviour

The brain and immune system are involved in an intricate network of bidirectional communication. This relationship is vital for optimal physiological and psychological development and functioning but can also result in unwanted outcomes. In particular, this interaction plays an important role in cognition, mood and behaviour. Neuroinflammation is known to contribute to neurological and affective disorders including impaired learning and memory, depressive, anxiety and schizoaffective symptoms, as well as pain. The development of these conditions often occurs on the backdrop of pre-existing physical illnesses which give rise to increased activation of the immune system, such as cancer, obesity, infection and autoimmune disorders. Similarly, psychological states can alter regulation of the immune system. This has been most extensively studied in the context of stress and immune function. Understanding the underlying mechanisms that lead to the onset of inflammation-induced neuropathology and stress-induced immune suppression will contribute to the development of novel and effective treatment strategies for both the disease and its neurological side effects. In this research topic we explored the relationship between the immune system and the brain throughout life. We include both original research and review papers from animal, clinical and molecular perspectives

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Neuroinflammation and Behaviour

EDITORIAL
published: 02 June 2015
doi: 10.3389/fnins.2015.00201
Frontiers in Neuroscience | www.frontiersin.org 1 June 2015 | Volume 9 | Article 201
Edited and reviewed by:
Hubert Vaudry,
University of Rouen, France
*Correspondence:
Luba Sominsky,
luba.sominsky@rmit.edu.au
Specialty section:
This article was submitted to
Neuroendocrine Science,
a section of the journal
Frontiers in Neuroscience
Received: 13 May 2015
Accepted: 21 May 2015
Published: 02 June 2015
Citation:
Sominsky L, Walker AK and Hodgson
DM (2015) Editorial:
Neuroinflammation and behavior.
Front. Neurosci. 9:201.
doi: 10.3389/fnins.2015.00201
Editorial: Neuroinflammation and
behavior
Luba Sominsky 1*, Adam K. Walker 2, 3 and Deborah M. Hodgson 4
1 School of Health Sciences, Health Innovations Research Institute, RMIT University, Melbourne, VIC, Australia, 2 Laboratory
of Neuroimmunology, Division of Internal Medicine, Department of Symptom Research, The University of Texas MD Anderson
Cancer Center, Houston, TX, USA, 3Neuroendocrine Regulation of Cancer Laboratory, Monash Institute of Pharmaceutical
Sciences, Monash University, Melbourne, VIC, Australia, 4 Laboratory of Neuroimmunology, Faculty of Science and IT, School
of Psychology, The University of Newcastle, Newcastle, NSW, Australia
Keywords: neuroinflammation, neuroimmune, neuroendocrine, proinflammatory, mood disorders, microglia,
perinatal programming, aging
Neuroimmune regulation plays a major role in many facets of human health. In the last 30
years our understanding of this intricate relationship between the brain and immune system has
progressed immensely. Pioneering work in the late 1980s and early 1990s began to establish an
understanding of the bi-directional communication between these previously considered distinct
systems, and its implications in the regulation of mood and cognition (Dantzer and Kelley, 1989;
Kelley and Dantzer, 1990; Bluthe et al., 1991). Since then, significant advances in the field of
neuroimmunology have been made, and we now know considerably more about the mechanisms
responsible for neuroimmune regulation of health and behavior. In this Frontiers research topic
Neuroinflammation and Behavior, 10 groups of researchers contributed their expertise to discuss
the recent knowledge in the field of neuroimmunology, focusing on the neuroinflammatory
mechanisms in affective disorders, early life programming of neuroimmune function, as well as
neuroimmune interactions in the aging brain and its associated pathologies.
Anisman and colleagues begin this topic with a review on the role of proinflammatory
cytokines in depressive disorders, and the ability of social experiences to cause, exacerbate or
mitigate cytokine imbalance and mood disorders. The authors provide evidence for a particular
contribution of individual factors, such as sex, age, genetic, and other differences, to the
effectiveness of social support in alleviating the symptoms of depression and neuroinflammatory
signaling (Audet et al., 2014). Hutchinson and colleagues expand on this discussion by exploring
the specific contribution of the innate immune pattern recognition receptor Toll-like receptor
4 (TLR4) in the pathophysiology of depression. The authors suggest that TLR4-mediated
mechanisms could underpin the neural, immune, and neuroendocrine alterations seen in patients
with major depressive disorder (Liu et al., 2014). Wohleb et al. propose a novel model of
neuroimmune interactions that underlie psychosocial stress-induced immune and behavioral
changes. In response to stress, simultaneous activation of peripheral monocytes and microglia
induces peripheral and central inflammation. Neuroendocrine and sympathetic stress responses
then promote monocyte trafficking to the brain and exacerbate microglial activation. This in
turn contributes to the behavioral phenotype, such as persistent anxiety-like behavior (Wohleb
et al., 2014). Baune and colleagues discuss the role of inflammasomes in neuroinflammation.
Inflammasomes, by promoting the processing and activation of proinflammatory cytokines,
play an instrumental role in the pathophysiology of neuroinflammation in the aging
brain, as well as in the etiologies of several neurological diseases. Inflammasome-driven
inflammation is also involved in the development of metabolic disorders that are known
to be associated with mental illness (Singhal et al., 2014). This review highlights the
therapeutic potential of targeting inflammasome-related pathways to combat neuroinflammatory
diseases.
Sominsky et al. Neuroinflammation and behavior
Several articles highlight the importance of early life
events in the development of the neuroimmune circuitries.
Campbell et al. investigate the role of the early microbial
environment in the development of stress and nociceptive
circuitries. The authors demonstrate that neonatal exposure
to an immune challenge suppresses behavioral responses to
nociceptive stimuli in adulthood. This is associated with
increased activation of orexin neurons, implicated in stress
and pain processing, in hypothalamic subregions (Campbell
et al., 2015). These findings may have important implications
for targeting the orexin system for treatment of chronic
pain conditions, as well as highlighting the critical role
of the early life environment in determining later health
outcomes. The latter is further demonstrated by Spencer and
colleagues. These authors examine the long-term effects of
early nutritional environment on neuroinflammatory profile.
Neonatal overfeeding induces basal microgliosis and increased
neuronal activation in response to an immune challenge in
the paraventricular hypothalamus. Interestingly, this early life
intervention reduces central responses to the inflammatory
effects of adult short-term high-fat diet. Whether these findings
represent a suboptimal ability of neonatally overfed animals
to counter the adversity of high-fat diet or whether this is an
adaptive response, remains to be established (Cai et al., 2014).
Jasoni et al. elaborate on the impact of perinatal immune-brain
interaction by looking at maternal obesity-induced inflammation
and predisposition of offspring to neurobehavioral andmetabolic
diseases. This review points to the common link between
metabolic imbalance and neuroimmune activity and to the
ability of the maternal immune milieu to alter fetal brain
development and function long-term (Jasoni et al., 2014).
The neuroinflammatory effects of obesity and other metabolic
disorders persist throughout life, inducing cognitive dysfunction
and other neuropathologies. Jenkins and colleagues review
preclinical and clinical evidence concerning obesity and cognitive
decline, focusing on the potential inflammatory mechanisms
underpinning this neuropathology in obesity. The authors
conclude that exercise may be the most efficient strategy to
alleviate obesity-related cognitive impairment (Nguyen et al.,
2014).
Fuggle et al. review the evidence for the impact of
neuroimmune interactions in rheumatoid arthritis (RA) on the
pathophysiology of this autoimmune disease. RA patients suffer
from greater susceptibility to infections, further exacerbating
joint pain and swelling. Current biologic therapies target the
suppression of major inflammatory pathways involved in joint
inflammation, improving disease control and quality of life.
This, however, may result in even a greater susceptibility
to infections, stimulating disease flares (Fuggle et al., 2014).
This article highlights the importance of further research into
therapeutic interventions for RA, sufficient to maintain disease
remission, while preventing the degree of immunosuppression
that may increase the risk of infections and trigger RA
flares.
Finally, Walker and colleagues review the evidence that
neuroinflammation plays a role in the neurobehavioral toxicities
of chemotherapy. They focus on the common symptoms,
such as cognitive decline, neuropathy and fatigue. While
neuroinflammation has been thought to be the major mediator
of these symptoms, the authors propose additional mechanisms
may be involved, such as damage associated molecular patterns
(DAMPS) and mitochondrial dysfunction (Vichaya et al.,
2015). This article highlights the exciting potential for novel
interventions to alleviate chemotherapy-induced neurotoxicities,
significantly improving quality of life ofmany cancer patients and
survivors.
In summary, the articles presented in this research topic
provide a valuable insight into the importance of neuroimmune
regulation in health and disease, encompassing a wide scope
of conditions and presenting evidence for novel and intriguing
mechanisms that underlie the reciprocal nature of brain-immune
interactions.
References
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Frontiers in Neuroscience | www.frontiersin.org 2 June 2015 | Volume 9 | Article 201
Sominsky et al. Neuroinflammation and behavior
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Conflict of Interest Statement: The authors declare that the research was
conducted in the absence of any commercial or financial relationships that could
be construed as a potential conflict of interest.
Copyright © 2015 Sominsky, Walker and Hodgson. This is an open-access article
distributed under the terms of the Creative Commons Attribution License (CC BY).
The use, distribution or reproduction in other forums is permitted, provided the
original author(s) or licensor are credited and that the original publication in this
journal is cited, in accordance with accepted academic practice. No use, distribution
or reproduction is permitted which does not comply with these terms.
Frontiers in Neuroscience | www.frontiersin.org 3 June 2015 | Volume 9 | Article 201


Sominsky, Luba

Walker, AK

Hodgson, DM

Deakin Research Online

Walker, Adam K

Hodgson, Deborah M.

Monash University Research Portal

http://dx.doi.org/10.3389/fnins.2015.00201

Neuroinflammation and behaviour

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