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Article ; Online: Disrupting T cell memory to promote stress resilience: A role for CD74?

Vecchiarelli, Haley A / Tremblay, Marie-Ève

2023 Volume 114, Page(s) 240–241

Language	English
Publishing date	2023-08-31
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	639219-2
ISSN	1090-2139 ; 0889-1591
ISSN (online)	1090-2139
ISSN	0889-1591
DOI	10.1016/j.bbi.2023.08.011
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Zs.A 2276: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 327: Show issues

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Article ; Online: Local translation in microglial processes.

Vecchiarelli, Haley A / Tremblay, Marie-Ève

Nature neuroscience

2023 Volume 26, Issue 7, Page(s) 1140–1142

MeSH term(s)	Microglia ; Brain
Language	English
Publishing date	2023-06-13
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	1420596-8
ISSN	1546-1726 ; 1097-6256
ISSN (online)	1546-1726
ISSN	1097-6256
DOI	10.1038/s41593-023-01370-z
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Zs.A 4891: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 67: Show issues

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Article ; Online: Microglial Transcriptional Signatures in the Central Nervous System: Toward A Future of Unraveling Their Function in Health and Disease.

Vecchiarelli, Haley A / Tremblay, Marie-Ève

Annual review of genetics

2023 Volume 57, Page(s) 65–86

Abstract: Microglia, the resident immune cells of the central nervous system (CNS), are primarily derived from the embryonic yolk sac and make their way to the CNS during early development. They play key physiological and immunological roles across the life span, ... ...

Abstract	Microglia, the resident immune cells of the central nervous system (CNS), are primarily derived from the embryonic yolk sac and make their way to the CNS during early development. They play key physiological and immunological roles across the life span, throughout health, injury, and disease. Recent transcriptomic studies have identified gene transcript signatures expressed by microglia that may provide the foundation for unprecedented insights into their functions. Microglial gene expression signatures can help distinguish them from macrophage cell types to a reasonable degree of certainty, depending on the context. Microglial expression patterns further suggest a heterogeneous population comprised of many states that vary according to the spatiotemporal context. Microglial diversity is most pronounced during development, when extensive CNS remodeling takes place, and following disease or injury. A next step of importance for the field will be to identify the functional roles performed by these various microglial states, with the perspective of targeting them therapeutically.
MeSH term(s)	Microglia/physiology ; Central Nervous System ; Macrophages ; Transcriptome/genetics ; Gene Expression Profiling
Language	English
Publishing date	2023-06-29
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	207928-8
ISSN	1545-2948 ; 0066-4170 ; 0066-4197
ISSN (online)	1545-2948
ISSN	0066-4170 ; 0066-4197
DOI	10.1146/annurev-genet-022223-093643
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Zs.A 1109: Show issues

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Article: Enhancing axonal myelination in seniors: A review exploring the potential impact cannabis has on myelination in the aged brain.

Murray, Colin J / Vecchiarelli, Haley A / Tremblay, Marie-Ève

Frontiers in aging neuroscience

2023 Volume 15, Page(s) 1119552

Abstract: Consumption of cannabis is on the rise as public opinion trends toward acceptance and its consequent legalization. Specifically, the senior population is one of the demographics increasing their use of cannabis the fastest, but research aimed at ... ...

Abstract	Consumption of cannabis is on the rise as public opinion trends toward acceptance and its consequent legalization. Specifically, the senior population is one of the demographics increasing their use of cannabis the fastest, but research aimed at understanding cannabis' impact on the aged brain is still scarce. Aging is characterized by many brain changes that slowly alter cognitive ability. One process that is greatly impacted during aging is axonal myelination. The slow degradation and loss of myelin (i.e., demyelination) in the brain with age has been shown to associate with cognitive decline and, furthermore, is a common characteristic of numerous neurological diseases experienced in aging. It is currently not known what causes this age-dependent degradation, but it is likely due to numerous confounding factors (i.e., heightened inflammation, reduced blood flow, cellular senescence) that impact the many cells responsible for maintaining overall homeostasis and myelin integrity. Importantly, animal studies using non-human primates and rodents have also revealed demyelination with age, providing a reliable model for researchers to try and understand the cellular mechanisms at play. In rodents, cannabis was recently shown to modulate the myelination process. Furthermore, studies looking at the direct modulatory impact cannabis has on microglia, astrocytes and oligodendrocyte lineage cells hint at potential mechanisms to prevent some of the more damaging activities performed by these cells that contribute to demyelination in aging. However, research focusing on how cannabis impacts myelination in the aged brain is lacking. Therefore, this review will explore the evidence thus far accumulated to show how cannabis impacts myelination and will extrapolate what this knowledge may mean for the aged brain.
Language	English
Publishing date	2023-03-22
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2558898-9
ISSN	1663-4365
ISSN	1663-4365
DOI	10.3389/fnagi.2023.1119552
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Article: Microglia: A pharmacological target for the treatment of age-related cognitive decline and Alzheimer's disease.

McKee, Chloe G / Hoffos, Madison / Vecchiarelli, Haley A / Tremblay, Marie-Ève

Frontiers in pharmacology

2023 Volume 14, Page(s) 1125982

Abstract: As individuals age, microglia, the resident immune cells of the central nervous system (CNS), become less effective at preserving brain circuits. Increases in microglial inflammatory activity are thought to contribute to age-related declines in cognitive ...

Abstract	As individuals age, microglia, the resident immune cells of the central nervous system (CNS), become less effective at preserving brain circuits. Increases in microglial inflammatory activity are thought to contribute to age-related declines in cognitive functions and to transitions toward mild cognitive impairment (MCI) and Alzheimer's disease (AD). As microglia possess receptors for communicating with the CNS environment, pharmacological therapies targeting these pathways hold potential for promoting homeostatic microglial functions within the aging CNS. Preclinical and early phase clinical trials investigating the therapeutic effects of pharmacological agents acting on microglia, including reactive oxygen species, TREM2, fractalkine signaling, the complement cascade, and the NLRP3 inflammasome, are currently underway; however, important questions remain unanswered. Current challenges include target selectivity, as many of the signaling pathways are expressed in other cell types. Furthermore, microglia are a heterogenous cell population with transcriptomic, proteomic, and microscopy studies revealing distinct microglial states, whose activities and abundance shift across the lifespan. For example, homeostatic microglia can transform into pathological states characterized by markers of oxidative stress. Selective pharmacological targeting aimed at limiting transitions to pathological states or promoting homeostatic or protective states, could help to avoid potentially harmful off-target effects on beneficial states or other cell types. In this mini-review we cover current microglial pathways of interest for the prevention and treatment of age-related cognitive decline and CNS disorders of aging focusing on MCI and AD. We also discuss the heterogeneity of microglia described in these conditions and how pharmacological agents could target specific microglial states.
Language	English
Publishing date	2023-02-09
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2023.1125982
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Article ; Online: The endocannabinoid system as a putative target for the development of novel drugs for the treatment of psychiatric illnesses.

Hill, Matthew N / Haney, Margaret / Hillard, Cecilia J / Karhson, Debra S / Vecchiarelli, Haley A

Psychological medicine

2023 Volume 53, Issue 15, Page(s) 7006–7024

Abstract: Cannabis is well established to impact affective states, emotion and perceptual processing, primarily through its interactions with the endocannabinoid system. While cannabis use is quite prevalent in many individuals afflicted with psychiatric illnesses, ...

Abstract	Cannabis is well established to impact affective states, emotion and perceptual processing, primarily through its interactions with the endocannabinoid system. While cannabis use is quite prevalent in many individuals afflicted with psychiatric illnesses, there is considerable controversy as to whether cannabis may worsen these conditions or provide some form of therapeutic benefit. The development of pharmacological agents which interact with components of the endocannabinoid system in more localized and discrete ways then via phytocannabinoids found in cannabis, has allowed the investigation if direct targeting of the endocannabinoid system itself may represent a novel approach to treat psychiatric illness without the potential untoward side effects associated with cannabis. Herein we review the current body of literature regarding the various pharmacological tools that have been developed to target the endocannabinoid system, their impact in preclinical models of psychiatric illness and the recent data emerging of their utilization in clinical trials for psychiatric illnesses, with a specific focus on substance use disorders, trauma-related disorders, and autism. We highlight several candidate drugs which target endocannabinoid function, particularly inhibitors of endocannabinoid metabolism or modulators of cannabinoid receptor signaling, which have emerged as potential candidates for the treatment of psychiatric conditions, particularly substance use disorder, anxiety and trauma-related disorders and autism spectrum disorders. Although there needs to be ongoing clinical work to establish the potential utility of endocannabinoid-based drugs for the treatment of psychiatric illnesses, the current data available is quite promising and shows indications of several potential candidate diseases which may benefit from this approach.
MeSH term(s)	Humans ; Endocannabinoids ; Mental Disorders/drug therapy ; Anxiety ; Anxiety Disorders ; Cannabis ; Cannabinoid Receptor Agonists ; Hallucinogens
Chemical Substances	Endocannabinoids ; Cannabinoid Receptor Agonists ; Hallucinogens
Language	English
Publishing date	2023-09-06
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	217420-0
ISSN	1469-8978 ; 0033-2917
ISSN (online)	1469-8978
ISSN	0033-2917
DOI	10.1017/S0033291723002465
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Zs.B 1003: Show issues

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Article ; Online: Environmental Enrichment Engages Vesicular Zinc Signaling to Enhance Hippocampal Neurogenesis.

Chrusch, Michael J / Fu, Selena / Spanswick, Simon C / Vecchiarelli, Haley A / Patel, Payal P / Hill, Matthew N / Dyck, Richard H

Cells

2023 Volume 12, Issue 6

Abstract: Zinc is highly concentrated in synaptic vesicles throughout the mammalian telencephalon and, in particular, the hippocampal dentate gyrus. A role for zinc in modulating synaptic plasticity has been inferred, but whether zinc has a particular role in ... ...

Abstract	Zinc is highly concentrated in synaptic vesicles throughout the mammalian telencephalon and, in particular, the hippocampal dentate gyrus. A role for zinc in modulating synaptic plasticity has been inferred, but whether zinc has a particular role in experience-dependent plasticity has yet to be determined. The aim of the current study was to determine whether vesicular zinc is important for modulating adult hippocampal neurogenesis in an experience-dependent manner and, consequently, hippocampal-dependent behaviour. We assessed the role of vesicular zinc in modulating hippocampal neurogenesis and behaviour by comparing ZnT3 knockout (KO) mice, which lack vesicular zinc, to wild-type (WT) littermates exposed to either standard housing conditions (SH) or an enriched environment (EE). We found that vesicular zinc is necessary for a cascade of changes in hippocampal plasticity following EE, such as increases in hippocampal neurogenesis and elevations in mature brain-derived neurotrophic factor (mBDNF), but was otherwise dispensable under SH conditions. Using the Spatial Object Recognition task and the Morris Water task we show that, unlike WT mice, ZnT3 KO mice showed no improvements in spatial memory following EE. These experiments demonstrate that vesicular zinc is essential for the enhancement of adult hippocampal neurogenesis and behaviour following enrichment, supporting a role for zincergic neurons in contributing to experience-dependent plasticity in the hippocampus.
MeSH term(s)	Mice ; Animals ; Zinc ; Hippocampus/physiology ; Synaptic Vesicles ; Neurons ; Mice, Knockout ; Neurogenesis/physiology ; Mammals
Chemical Substances	Zinc (J41CSQ7QDS)
Language	English
Publishing date	2023-03-13
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells12060883
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Article ; Online: Neuroendocrine, neuroinflammatory and pathological outcomes of chronic stress: A story of microglial remodeling.

Picard, Katherine / St-Pierre, Marie-Kim / Vecchiarelli, Haley A / Bordeleau, Maude / Tremblay, Marie-Ève

Neurochemistry international

2021 Volume 145, Page(s) 104987

Abstract: Microglia, the resident macrophage cells of the central nervous system (CNS), are involved in a myriad of processes required to maintain CNS homeostasis. These cells are dynamic and can adapt their phenotype and functions to the physiological needs of ... ...

Abstract	Microglia, the resident macrophage cells of the central nervous system (CNS), are involved in a myriad of processes required to maintain CNS homeostasis. These cells are dynamic and can adapt their phenotype and functions to the physiological needs of the organism. Microglia rapidly respond to changes occurring in their microenvironment, such as the ones taking place during stress. While stress can be beneficial for the organism to adapt to a situation, it can become highly detrimental when it turns chronic. Microglial response to prolonged stress may lead to an alteration of their beneficial physiological functions, becoming either maladaptive or pro-inflammatory. In this review, we aim to summarize the effects of chronic stress exerted on microglia through the neuroendocrine system and inflammation at adulthood. We also discuss how these effects of chronic stress could contribute to microglial involvement in neuropsychiatric and sleep disorders, as well as neurodegenerative diseases.
MeSH term(s)	Animals ; Chronic Disease ; Corticosterone/metabolism ; Humans ; Inflammation/metabolism ; Inflammation/pathology ; Inflammation Mediators/metabolism ; Microglia/metabolism ; Microglia/pathology ; Neurodegenerative Diseases/metabolism ; Neurodegenerative Diseases/pathology ; Neurosecretory Systems/metabolism ; Neurosecretory Systems/pathology ; Norepinephrine/metabolism ; Reactive Oxygen Species/metabolism ; Stress, Psychological/metabolism ; Stress, Psychological/pathology
Chemical Substances	Inflammation Mediators ; Reactive Oxygen Species ; Corticosterone (W980KJ009P) ; Norepinephrine (X4W3ENH1CV)
Language	English
Publishing date	2021-02-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	283190-9
ISSN	1872-9754 ; 0197-0186
ISSN (online)	1872-9754
ISSN	0197-0186
DOI	10.1016/j.neuint.2021.104987
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Zs.A 1610: Show issues

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Article ; Online: Present and future of microglial pharmacology.

Šimončičová, Eva / Gonçalves de Andrade, Elisa / Vecchiarelli, Haley A / Awogbindin, Ifeoluwa O / Delage, Charlotte I / Tremblay, Marie-Ève

Trends in pharmacological sciences

2022 Volume 43, Issue 8, Page(s) 669–685

Abstract: Microglia, brain resident immune cells, modulate development, activity, and plasticity of the central nervous system. Mechanistically implicated in numerous neurological pathologies, microglia emerge as strong contenders for novel neurotherapies. ... ...

Abstract	Microglia, brain resident immune cells, modulate development, activity, and plasticity of the central nervous system. Mechanistically implicated in numerous neurological pathologies, microglia emerge as strong contenders for novel neurotherapies. Shifting away from merely an attenuation of excessive microglial inflammatory and phagocytic activities, current therapies aim toward targeting the complex context-dependent microglial heterogeneity, unveiled by large-scale genetic studies and emerging single-cell analyses. Although lacking the necessary selectivity, initial therapies attempting to target specific state-associated microglial properties and functions (e.g., inflammatory activity, phagocytosis, proliferation, metabolism, or surveillance) are currently under pre- or even clinical (Phase I-IV) investigation. Here, we provide an update on current microglial therapeutic research and discuss what the future in the field might look like.
MeSH term(s)	Brain/metabolism ; Drug Delivery Systems ; Humans ; Microglia ; Phagocytosis/physiology
Language	English
Publishing date	2022-01-11
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	282846-7
ISSN	1873-3735 ; 0165-6147
ISSN (online)	1873-3735
ISSN	0165-6147
DOI	10.1016/j.tips.2021.11.006
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Zs.A 1513: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 6: Show issues

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Article: Microglia Fighting for Neurological and Mental Health: On the Central Nervous System Frontline of COVID-19 Pandemic.

Gonçalves de Andrade, Elisa / Šimončičová, Eva / Carrier, Micaël / Vecchiarelli, Haley A / Robert, Marie-Ève / Tremblay, Marie-Ève

Frontiers in cellular neuroscience

2021 Volume 15, Page(s) 647378

Abstract: Coronavirus disease 2019 (COVID-19) is marked by cardio-respiratory alterations, with increasing reports also indicating neurological and psychiatric symptoms in infected individuals. During COVID-19 pathology, the central nervous system (CNS) is ... ...

Abstract	Coronavirus disease 2019 (COVID-19) is marked by cardio-respiratory alterations, with increasing reports also indicating neurological and psychiatric symptoms in infected individuals. During COVID-19 pathology, the central nervous system (CNS) is possibly affected by direct severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) invasion, exaggerated systemic inflammatory responses, or hypoxia. Psychosocial stress imposed by the pandemic further affects the CNS of COVID-19 patients, but also the non-infected population, potentially contributing to the emergence or exacerbation of various neurological or mental health disorders. Microglia are central players of the CNS homeostasis maintenance and inflammatory response that exert their crucial functions in coordination with other CNS cells. During homeostatic challenges to the brain parenchyma, microglia modify their density, morphology, and molecular signature, resulting in the adjustment of their functions. In this review, we discuss how microglia may be involved in the neuroprotective and neurotoxic responses against CNS insults deriving from COVID-19. We examine how these responses may explain, at least partially, the neurological and psychiatric manifestations reported in COVID-19 patients and the general population. Furthermore, we consider how microglia might contribute to increased CNS vulnerability in certain groups, such as aged individuals and people with pre-existing conditions.
Language	English
Publishing date	2021-02-18
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2452963-1
ISSN	1662-5102
ISSN	1662-5102
DOI	10.3389/fncel.2021.647378
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