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Article: The HPA - Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the Brain.

Bellavance, Marc-André / Rivest, Serge

2014 Volume 5, Page(s) 136

Abstract: In response to physiological and psychogenic stressors, the hypothalamic-pituitary-adrenal (HPA) axis orchestrates the systemic release of glucocorticoids (GCs). By virtue of nearly ubiquitous expression of the GC receptor and the multifaceted metabolic, ...

Abstract	In response to physiological and psychogenic stressors, the hypothalamic-pituitary-adrenal (HPA) axis orchestrates the systemic release of glucocorticoids (GCs). By virtue of nearly ubiquitous expression of the GC receptor and the multifaceted metabolic, cardiovascular, cognitive, and immunologic functions of GCs, this system plays an essential role in the response to stress and restoration of an homeostatic state. GCs act on almost all types of immune cells and were long recognized to perform salient immunosuppressive and anti-inflammatory functions through various genomic and non-genomic mechanisms. These renowned effects of the steroid hormone have been exploited in the clinic for the past 70 years and synthetic GC derivatives are commonly used for the therapy of various allergic, autoimmune, inflammatory, and hematological disorders. The role of the HPA axis and GCs in restraining immune responses across the organism is however still debated in light of accumulating evidence suggesting that GCs can also have both permissive and stimulatory effects on the immune system under specific conditions. Such paradoxical actions of GCs are particularly evident in the brain, where substantial data support either a beneficial or detrimental role of the steroid hormone. In this review, we examine the roles of GCs on the innate immune system with a particular focus on the CNS compartment. We also dissect the numerous molecular mechanisms through which GCs exert their effects and discuss the various parameters influencing the paradoxical immunomodulatory functions of GCs in the brain.
Language	English
Publishing date	2014-03-31
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2606827-8
ISSN	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2014.00136
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Article: Bacterial, fungal, and mycorrhizal communities in the soil differ between clearcuts and insect outbreaks in the boreal forest 50 years after disturbance

Bell-Doyon, Philip / Bellavance, Virginie / Bélanger, Louis / Mazerolle, Marc J. / Carlos Villarreal A, Juan

Forest ecology and management. 2022 Aug. 21,

2022

Abstract: Soil microorganisms influence the functions and processes of forest ecosystems, and their composition is affected by natural and anthropogenic disturbances. Timber harvesting disturbs boreal soil microbiomes, most notably ectomycorrhizal communities ... ...

Abstract	Soil microorganisms influence the functions and processes of forest ecosystems, and their composition is affected by natural and anthropogenic disturbances. Timber harvesting disturbs boreal soil microbiomes, most notably ectomycorrhizal communities which are reportedly less diverse in the first decade following a clearcut. However, the long-term impact of harvesting on forest soil microorganism communities have rarely been investigated nor compared with natural disturbances. Our objective was to compare the composition and diversity of bacterial, fungal, and mycorrhizal communities between boreal old-growth and nearby 50–year–old stands regenerating after either an insect outbreak or a clearcut. Our main hypothesis was that the nature of the stand–replacing disturbance influences the composition of the soil microbiome, and that the effect is still detectable 50 years later. We collected 90 samples from 30 plots across six forest stands dominated by Abies balsamea. We sequenced the genome regions 16S rRNA v3v4 for bacteria and ITS1 for fungi and we constructed distance matrices to evaluate changes in community composition with permutational analyses of variance. Results show that 10.2% to 12.4% of the variability in community composition can be explained by stand type alone for bacteria, fungi, and mycorrhizae. The composition of soil microbiomes did not vary with soil physicochemical properties. Stands regenerating after a clearcut had a greater alpha diversity (H’) of fungi and mycorrhizae than stands regenerating after an insect outbreak, while old–growth stands were intermediate. Our data indicate that soil microbiomes associated with natural disturbance dynamics differ from those of clearcutted stands, although the mechanisms underlying this pattern remain unclear. Therefore, we suggest that forest managers spare the largest possible tracts of unmanaged forests across the harvested landscape, including areas affected by natural disturbances, so that benchmark soil communities remain available for future studies.
Keywords	Abies balsamea ; administrative management ; boreal forests ; clearcutting ; community structure ; ectomycorrhizae ; forest ecology ; forest soils ; fungi ; genome ; insect outbreaks ; insects ; landscapes ; long term effects ; soil microorganisms ; species diversity ; variance
Language	English
Dates of publication	2022-0821
Publishing place	Elsevier B.V.
Document type	Article
Note	Pre-press version
ZDB-ID	751138-3
ISSN	0378-1127
ISSN	0378-1127
DOI	10.1016/j.foreco.2022.120493
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Article ; Online: The neuroendocrine control of the innate immune system in health and brain diseases.

Bellavance, Marc-André / Rivest, Serge

Immunological reviews

2012 Volume 248, Issue 1, Page(s) 36–55

Abstract: The innate immune reaction takes place in the brain during immunogenic challenges, injury, and disease. Such a response is highly regulated by numerous anti-inflammatory mechanisms that may directly affect the ultimate consequences of such a reaction ... ...

Abstract	The innate immune reaction takes place in the brain during immunogenic challenges, injury, and disease. Such a response is highly regulated by numerous anti-inflammatory mechanisms that may directly affect the ultimate consequences of such a reaction within the cerebral environment. The neuroendocrine control of this innate immune system by glucocorticoids is critical for the delicate balance between cell survival and damage in the presence of inflammatory mediators. Glucocorticoids play key roles in regulating the expression of inflammatory genes, and they also have the ability to modulate numerous functions that may ultimately lead to brain damage or repair after injury. Here we review these mechanisms and discuss data supporting both neuroprotective and detrimental roles of the neuroendocrine control of innate immunity.
MeSH term(s)	Animals ; Brain Diseases/immunology ; Brain Diseases/metabolism ; Central Nervous System/drug effects ; Central Nervous System/immunology ; Glucocorticoids/pharmacology ; Humans ; Hypothalamo-Hypophyseal System/immunology ; Hypothalamo-Hypophyseal System/metabolism ; Immunity, Innate ; Microglia/immunology ; Microglia/metabolism ; Neurosecretory Systems/immunology ; Neurosecretory Systems/metabolism ; Pituitary-Adrenal System/immunology ; Pituitary-Adrenal System/metabolism ; Signal Transduction
Chemical Substances	Glucocorticoids
Language	English
Publishing date	2012-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	391796-4
ISSN	1600-065X ; 0105-2896
ISSN (online)	1600-065X
ISSN	0105-2896
DOI	10.1111/j.1600-065X.2012.01129.x
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Article ; Online: Role of adaptor protein MyD88 in TLR-mediated preconditioning and neuroprotection after acute excitotoxicity.

Larochelle, Antoine / Bellavance, Marc-André / Rivest, Serge

Brain, behavior, and immunity

2015 Volume 46, Page(s) 221–231

Abstract: Excitotoxic cell death is a crucial mechanism through which neurodegeneration occurs in numerous pathologies of the central nervous system (CNS), such as Alzheimer's disease, stroke and spinal cord injury. Toll-like receptors (TLRs) are strongly ... ...

Abstract	Excitotoxic cell death is a crucial mechanism through which neurodegeneration occurs in numerous pathologies of the central nervous system (CNS), such as Alzheimer's disease, stroke and spinal cord injury. Toll-like receptors (TLRs) are strongly expressed on microglial cells and are key regulators of the innate immune response to neuronal damage. However, it is still unclear whether their stimulation is protective or harmful in excitotoxic contexts. In this study, we demonstrate that systemic administration of lipopolysaccharide (LPS) or Pam3CSK4 24h prior to an intrastriatal injection of kainic acid (KA) significantly protected cortical neurons in the acute phase of injury. Protection could not be detected with the TLR3 ligand poly-IC. Histological analyses revealed that microglia of LPS and Pam3CSK4 pre-conditioned group were primed to react to injury and exhibited a stronger expression of Tnf and Tlr2 mRNA. We also found that mice deficient for MyD88, a critical adaptor protein for most TLR, were more vulnerable than WT mice to KA-induced excitotoxicity at early (12h and 24h) and late (10days) time points. Finally, bone-marrow chimeric mice revealed that MyD88 signaling in CNS resident cells, but not in cells of hematopoietic origin, mediates the protective effect. This study unravels the potential of TLR2 and TLR4 agonists to induce a protective state of preconditioning against KA-mediated excitotoxicity and further highlights the beneficial role of cerebral MyD88 signaling in this context.
MeSH term(s)	Animals ; Cell Death/drug effects ; Cell Death/physiology ; Kainic Acid/toxicity ; Lipopeptides/pharmacology ; Lipopolysaccharides ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Myeloid Differentiation Factor 88/genetics ; Myeloid Differentiation Factor 88/metabolism ; Neurons/drug effects ; Neurons/metabolism ; Neuroprotection/physiology ; Signal Transduction/drug effects ; Signal Transduction/physiology ; Toll-Like Receptors/genetics ; Toll-Like Receptors/metabolism
Chemical Substances	Lipopeptides ; Lipopolysaccharides ; Myeloid Differentiation Factor 88 ; Pam(3)CSK(4) peptide ; Toll-Like Receptors ; Kainic Acid (SIV03811UC)
Language	English
Publishing date	2015-05
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639219-2
ISSN	1090-2139 ; 0889-1591
ISSN (online)	1090-2139
ISSN	0889-1591
DOI	10.1016/j.bbi.2015.02.019
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Article ; Online: Texting while walking: An expensive switch cost.

Courtemanche, Francois / Labonté-LeMoyne, Elise / Léger, Pierre-Majorique / Fredette, Marc / Senecal, Sylvain / Cameron, Ann-Frances / Faubert, Jocelyn / Bellavance, Francois

Accident; analysis and prevention

2019 Volume 127, Page(s) 1–8

Abstract: Texting while walking has been highlighted as a dangerous behavior that leads to impaired judgment and accidents. This impairment could be due to task switching which involves activation of the present task and the inhibition of the previous task. ... ...

Abstract	Texting while walking has been highlighted as a dangerous behavior that leads to impaired judgment and accidents. This impairment could be due to task switching which involves activation of the present task and the inhibition of the previous task. However, the relative contributions of these processes and their brain activity have not yet been studied. We addressed this gap by asking participants to discriminate the orientation of an oncoming human shape in a virtual environment while they were: i) walking on a treadmill, or ii) texting while walking on a treadmill. Participants' performance (i.e., correctly identifying if a walker would pass them to their left or right) and electroencephalography (EEG) data was collected. Unsurprisingly, we found that participants performed better while they were only walking than when texting while walking. However, we also found that the diminished performance is differently related to task set inhibition and task set activation in the two conditions. The alpha oscillations, which can be used as an index of task inhibition, have a significantly different relation to performance in the two conditions, the relation being negative when subjects are texting. This may indicate that the more inhibition is needed, the more the performance is affected by texting. To our knowledge, this is the first study to investigate the brain signature of task switching in texting while walking. This finding is the first step in identifying the source of impaired judgment in texting pedestrians and in finding viable solutions to reduce the risks.
MeSH term(s)	Adult ; Attention/physiology ; Case-Control Studies ; Exercise Test/methods ; Female ; Humans ; Male ; Orientation, Spatial/physiology ; Pedestrians ; Task Performance and Analysis ; Text Messaging ; Walking/physiology
Language	English
Publishing date	2019-02-28
Publishing country	England
Document type	Journal Article
ZDB-ID	210223-7
ISSN	1879-2057 ; 0001-4575
ISSN (online)	1879-2057
ISSN	0001-4575
DOI	10.1016/j.aap.2019.02.022
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Article: Bone marrow-derived macrophages and the CNS: An update on the use of experimental chimeric mouse models and bone marrow transplantation in neurological disorders.

Larochelle, Antoine / Bellavance, Marc-André / Michaud, Jean-Philippe / Rivest, Serge

Biochimica et biophysica acta

2015 Volume 1862, Issue 3, Page(s) 310–322

Abstract: ... the landmark studies that used chimeric mice to characterize the roles of microglia and BMDM ... and Markus Schwaninger. ...

Abstract	The central nervous system (CNS) is a very unique system with multiple features that differentiate it from systemic tissues. One of the most captivating aspects of its distinctive nature is the presence of the blood brain barrier (BBB), which seals it from the periphery. Therefore, to preserve tissue homeostasis, the CNS has to rely heavily on resident cells such as microglia. These pivotal cells of the mononuclear lineage have important and dichotomous roles according to various neurological disorders. However, certain insults can overwhelm microglia as well as compromising the integrity of the BBB, thus allowing the infiltration of bone marrow-derived macrophages (BMDMs). The use of myeloablation and bone marrow transplantation allowed the generation of chimeric mice to study resident microglia and infiltrated BMDM separately. This breakthrough completely revolutionized the way we captured these 2 types of mononuclear phagocytic cells. We now realize that microglia and BMDM exhibit distinct features and appear to perform different tasks. Since these cells are central in several pathologies, it is crucial to use chimeric mice to analyze their functions and mechanisms to possibly harness them for therapeutic purpose. This review will shed light on the advent of this methodology and how it allowed deciphering the ontology of microglia and its maintenance during adulthood. We will also compare the different strategies used to perform myeloablation. Finally, we will discuss the landmark studies that used chimeric mice to characterize the roles of microglia and BMDM in several neurological disorders. This article is part of a Special Issue entitled: Neuro Inflammation edited by Helga E. de Vries and Markus Schwaninger.
MeSH term(s)	Animals ; Bone Marrow Transplantation/methods ; Brain/metabolism ; Brain/pathology ; Central Nervous System/metabolism ; Central Nervous System/pathology ; Disease Models, Animal ; Humans ; Macrophages/metabolism ; Macrophages/pathology ; Mice ; Mice, Transgenic ; Microglia/metabolism ; Microglia/pathology ; Nervous System Diseases/genetics ; Nervous System Diseases/pathology
Language	English
Publishing date	2015-10-08
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	60-7
ISSN	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
ISSN (online)	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
ISSN	0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
DOI	10.1016/j.bbadis.2015.09.017
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Article: IL-1RAcPb signaling regulates adaptive mechanisms in neurons that promote their long-term survival following excitotoxic insults.

Gosselin, David / Bellavance, Marc-André / Rivest, Serge

Frontiers in cellular neuroscience

2013 Volume 7, Page(s) 9

Abstract: Excitotoxicity is a major component of neurodegenerative diseases and is typically accompanied by an inflammatory response. Cytokines IL-1alpha and IL-1beta are key regulators of this inflammatory response and modulate the activity of numerous cell types, ...

Abstract	Excitotoxicity is a major component of neurodegenerative diseases and is typically accompanied by an inflammatory response. Cytokines IL-1alpha and IL-1beta are key regulators of this inflammatory response and modulate the activity of numerous cell types, including neurons. IL-1RAcPb is an isoform of IL-1RAcP expressed specifically in neurons and promotes their survival during acute inflammation. Here, we investigated in vivo whether IL-1RAcPb also promotes neuronal survival in a model of excitotoxicity. Intrastriatal injection of kainic acid (KA) in mice caused a strong induction of IL-1 cytokines mRNA in the brain. The stress response of cortical neurons at 12 h post-injection, as measured by expression of Atf3, FoxO3a, and Bdnf mRNAs, was similar in WT and AcPb-deficient mice. Importantly however, a delayed upregulation in the transcription of calpastatin was significantly higher in WT than in AcPb-deficient mice. Finally, although absence of AcPb signaling had no effect on damage to neurons in the cortex at early time points, it significantly impaired their long-term survival. These data suggest that in a context of excitotoxicity, stimulation of IL-1RAcPb signaling may promote the activity of a key neuroprotective mechanism.
Language	English
Publishing date	2013-02-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2452963-1
ISSN	1662-5102
ISSN	1662-5102
DOI	10.3389/fncel.2013.00009
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Article ; Online: Using a smartphone while walking: The cost of smartphone-addiction proneness.

Mourra, Gabrielle Naïmé / Sénécal, Sylvain / Fredette, Marc / Lepore, Franco / Faubert, Jocelyn / Bellavance, François / Cameron, Ann-Frances / Labonté-LeMoyne, Élise / Léger, Pierre-Majorique

Addictive behaviors

2020 Volume 106, Page(s) 106346

Abstract: Distracted walking is an ever-increasing problem. Studies have already shown that using a smartphone while walking impairs attention and increases the risk of accidents. This study seeks to determine if smartphone-addiction proneness magnifies the risks ... ...

Abstract	Distracted walking is an ever-increasing problem. Studies have already shown that using a smartphone while walking impairs attention and increases the risk of accidents. This study seeks to determine if smartphone-addiction proneness magnifies the risks of using a smartphone while walking. In an experimental design, participants, while walking on a treadmill and engaged in a smartphone task, were required to switch tasks by responding to an external stimulus, i.e., determining the direction of movement of a point-light walker. Participants were chosen to cover a range of smartphone-addiction proneness. Four smartphone-use conditions were simulated: a control condition with no smartphone-use, an individual conversation condition, a gaming condition, and a group conversation condition. Our results show that using a smartphone while walking decreases accuracy and increases the number of missed stimuli. Moreover, participants with higher smartphone-addiction proneness scores were also prone to missing more stimuli, and this effect was found regardless of experimental condition. The effect of the smartphone task on accuracy and the number of missed stimuli was mediated by the emotional arousal caused by the smartphone task. Smartphone-addiction proneness was positively correlated with a declared frequency of smartphone use while walking. Furthermore, of all the smartphone tasks, the gaming condition was found to be the most distracting.
MeSH term(s)	Attention ; Humans ; Smartphone ; Surveys and Questionnaires ; Walking
Language	English
Publishing date	2020-02-05
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	197618-7
ISSN	1873-6327 ; 0306-4603
ISSN (online)	1873-6327
ISSN	0306-4603
DOI	10.1016/j.addbeh.2020.106346
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Article ; Online: Measuring the Switch Cost of Smartphone Use While Walking.

Mourra, Gabrielle Naïmé / Brieugne, David / Rucco, Emma / Labonté-Lemoyne, Élise / Courtemanche, François / Sénécal, Sylvain / Fredette, Marc / Cameron, Ann-Frances / Faubert, Jocelyn / Lepore, Franco / Bellavance, François / Léger, Pierre-Majorique

Journal of visualized experiments : JoVE

2020 , Issue 158

Abstract: This paper presents a study protocol to measure the task-switching cost of using a smartphone while walking. This method involves having participants walk on a treadmill under two experimental conditions: a control condition (i.e., simply walking) and a ... ...

Abstract	This paper presents a study protocol to measure the task-switching cost of using a smartphone while walking. This method involves having participants walk on a treadmill under two experimental conditions: a control condition (i.e., simply walking) and a multitasking condition (i.e., texting while walking). During these conditions, the participants must switch between the tasks related to the experimental condition and a direction determining task. This direction task is done with a point-light walker figure, seemingly walking towards the left or the right of the participant. Performance on the direction task represents the participant's task-switching costs. There were two performance measures: 1) correct identification of the direction and 2) response time. EEG data are recorded in order to measure the alpha oscillations and cognitive engagement occurring during the task switch. This method is limited in its ecological validity: pedestrian environments have many stimuli occurring simultaneously and competing for attention. Nonetheless, this method is appropriate for pinpointing task-switching costs. The EEG data allow the study of the underlying mechanisms in the brain that are related to differing task-switching costs. This design allows the comparison between task switching when doing one task at a time, as compared to task switching when multitasking, prior to the stimulus presentation. This allows understanding and pinpointing both the behavioral and neurophysiological impact of these two different task-switching conditions. Furthermore, by correlating the task-switching costs with the brain activity, we can learn more about what causes these behavioral effects. This protocol is an appropriate base for studying the switching cost of different smartphone uses. Different tasks, questionnaires, and other measures can be added to it in order to understand the different factors involved in the task-switching cost of smartphone use while walking.
MeSH term(s)	Attention/physiology ; Brain/physiology ; Electroencephalography/methods ; Exercise ; Humans ; Psychomotor Performance/physiology ; Reaction Time/physiology ; Smartphone/instrumentation ; Smartphone/statistics & numerical data ; Walking/physiology
Language	English
Publishing date	2020-04-30
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Video-Audio Media
ZDB-ID	2259946-0
ISSN	1940-087X ; 1940-087X
ISSN (online)	1940-087X
ISSN	1940-087X
DOI	10.3791/60555
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Article ; Online: Real-time in vivo imaging reveals the ability of monocytes to clear vascular amyloid beta.

Michaud, Jean-Philippe / Bellavance, Marc-André / Préfontaine, Paul / Rivest, Serge

Cell reports

2013 Volume 5, Issue 3, Page(s) 646–653

Abstract: Alzheimer's disease (AD) is characterized by the accumulation of amyloid beta (Aβ) that is assumed to result from impaired elimination of this neurotoxic peptide. Most patients with AD also exhibit cerebral amyloid angiopathy, which consists of Aβ ... ...

Abstract	Alzheimer's disease (AD) is characterized by the accumulation of amyloid beta (Aβ) that is assumed to result from impaired elimination of this neurotoxic peptide. Most patients with AD also exhibit cerebral amyloid angiopathy, which consists of Aβ deposition within the cerebral vasculature. The contribution of monocytes in AD has so far been limited to macrophage precursors. In this study, we aimed to investigate whether circulating monocytes could play a role in the elimination of Aβ. With live intravital two-photon microscopy, we demonstrate that patrolling monocytes are attracted to and crawl onto the luminal walls of Aβ-positive veins, but not on Aβ-positive arteries or Aβ-free blood vessels. Additionally, we report the presence of crawling monocytes carrying Aβ in veins and their ability to circulate back into the bloodstream. Selective removal of Ly6C(lo) monocytes in APP/PS1 mice induced a significant increase of Aβ load in the cortex and hippocampus. These data uncover the ability of Ly6C(lo) monocytes to naturally target and eliminate Aβ within the lumen of veins and constitute a potential therapeutic target in AD.
MeSH term(s)	Alzheimer Disease/blood ; Alzheimer Disease/pathology ; Amyloid beta-Peptides/blood ; Animals ; Blood Vessels/metabolism ; Blood Vessels/pathology ; Image Processing, Computer-Assisted/methods ; Leukocytes, Mononuclear/metabolism ; Mice ; Mice, Inbred C57BL ; Microscopy, Fluorescence, Multiphoton/methods
Chemical Substances	Amyloid beta-Peptides
Language	English
Publishing date	2013-11-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2013.10.010
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