Microglial depletion disrupts normal functional development of adult-born neurons in the olfactory bulb DOI Creative Commons
Jenelle L. Wallace,

Julia Lord,

Lasse Dissing‐Olesen

et al.

eLife, Journal Year: 2020, Volume and Issue: 9

Published: March 6, 2020

Microglia play key roles in regulating synapse development and refinement the developing brain, but it is unknown whether they are similarly involved during adult neurogenesis. By transiently depleting microglia from healthy mouse we show that necessary for normal functional of adult-born granule cells (abGCs) olfactory bulb. Microglial depletion reduces odor responses developing, not preexisting GCs vivo both awake anesthetized mice. preferentially target their motile processes to interact with mushroom spines on abGCs, when absent, abGCs develop smaller receive weaker excitatory synaptic inputs. These results suggest promote synapses onto which may impact function these circuit.

Language: Английский

Chemogenetic manipulation of microglia inhibits neuroinflammation and neuropathic pain in mice DOI
Min‐Hee Yi, Yong Liu, Kevin Liu

et al.

Brain Behavior and Immunity, Journal Year: 2020, Volume and Issue: 92, P. 78 - 89

Published: Nov. 20, 2020

Language: Английский

Citations

112
Behavioral Assessment of Sensory, Motor, Emotion, and Cognition in Rodent Models of Intracerebral Hemorrhage DOI Creative Commons
Xiaoyu Shi,

Huiying Bai,

Junmin Wang

et al.

Frontiers in Neurology, Journal Year: 2021, Volume and Issue: 12

Published: June 17, 2021

Intracerebral hemorrhage (ICH) is the second most common type of stroke and has one highest fatality rates any disease. There are many clinical signs symptoms after ICH due to brain cell injury network disruption resulted from rupture a tiny artery activation inflammatory cells, such as motor dysfunction, sensory impairment, cognitive emotional disturbance, etc. Thus, researchers have established tests evaluate behavioral changes in rodent models, order achieve better understanding thus improvements prognosis for treatment stroke. This review summarizes existing protocols that been applied assess neurologic function outcomes models pain, motor, cognition, emotion tests. Pain include mechanical, hot, cold pain tests; following 12 types: deficit scale test, staircase rotarod cylinder grid walk forelimb placing wire hanging modified severity score, beam walking horizontal ladder adhesive removal test; learning memory Morris water maze, Y-maze, novel object recognition elevated plus sucrose preference tail suspension open field forced swim test. discusses these assessments by examining their rationale, setup, duration, baseline, procedures well comparing pros cons, guiding select appropriate preclinical research.

Language: Английский

Citations

104
Anxiety and hippocampal neuronal activity: Relationship and potential mechanisms DOI Open Access
Maedeh Ghasemi, Mojdeh Navidhamidi, Fatemeh Rezaei

et al.

Cognitive Affective & Behavioral Neuroscience, Journal Year: 2021, Volume and Issue: 22(3), P. 431 - 449

Published: Dec. 6, 2021

Language: Английский

Citations

95
Microglial P2Y12 Receptor Regulates Seizure-Induced Neurogenesis and Immature Neuronal Projections DOI Creative Commons
Mingshu Mo, Ukpong B. Eyo, Manling Xie

et al.

Journal of Neuroscience, Journal Year: 2019, Volume and Issue: 39(47), P. 9453 - 9464

Published: Oct. 9, 2019

Seizures are common in humans with various etiologies ranging from congenital aberrations to acute injuries that alter the normal balance of brain excitation and inhibition. A notable consequence seizures is induction aberrant neurogenesis increased immature neuronal projections. However, regulatory mechanisms governing these features during epilepsy development not fully understood. Recent studies show microglia, brain's resident immune cell, contribute regulate seizure phenotypes. role microglia neurogenic contexts has been adequately investigated. To address this question, we coupled intracerebroventricular kainic acid model current pharmacogenetic approaches eliminate male mice. We promote seizure-induced subsequent projections above below pyramidal neurons between DG CA3 regions. Furthermore, identify microglial P2Y12 receptors (P2Y12R) as a participant process. Together, our results implicate P2Y12R signaling epileptogenesis provide further evidence for targeting general specific ameliorate proepileptogenic processes.SIGNIFICANCE STATEMENT Epileptogenesis process by which develops epilepsy. Several processes have identified confer such epileptic characteristics, including Understanding changes critical developing therapies restrain epileptogenesis. investigated purinergic selectively expressed cells. report, first time, both These indicate enhance promoting suggest axis could be novel therapeutic strategy clinic.

Language: Английский

Citations

78
Plasticity of microglia DOI
Marcus Augusto‐Oliveira, Gabriela de Paula Arrifano,

Charlotte Delage

et al.

Biological reviews/Biological reviews of the Cambridge Philosophical Society, Journal Year: 2021, Volume and Issue: 97(1), P. 217 - 250

Published: Sept. 21, 2021

ABSTRACT Microglial cells are the scions of foetal macrophages which invade neural tube early during embryogenesis. The nervous tissue environment instigates phenotypic metamorphosis into idiosyncratic surveilling microglia, generally characterised by a small cell body and highly ramified motile processes that constantly scan for signs changes in homeostasis allow microglia to perform crucial homeostatic functions. microglial phenotype is evolutionarily conserved from invertebrates humans. Despite this evolutionary conservation, show substantial heterogeneity their gene protein expression, as well morphological appearance. These differences age, region context specific reflect high degree plasticity underlying life‐long adaptation supporting exceptional adaptive capacity central system. Microgliocytes essential elements cellular network formation refinement developing tissue. Several distinct patrolling modes contribute formation, modification, pruning synapses; support protection neurones through microglial–somatic junctions; control neuronal axonal excitability microglia–axonal contacts. In pathology, undergo proliferation reactive remodelling known microgliosis, dependent, yet represents an defence response. Microgliosis results emergence multiple disease context‐specific states; addition, neuropathology associated with appearance protective or recovery forms. summary, supports development functional activity healthy provides sophisticated defences against disease.

Language: Английский

Citations

78
Microglial Inflammatory-Metabolic Pathways and Their Potential Therapeutic Implication in Major Depressive Disorder DOI Creative Commons
Reza Rahimian, Claudia Belliveau, Rebecca Chen

et al.

Frontiers in Psychiatry, Journal Year: 2022, Volume and Issue: 13

Published: June 16, 2022

Increasing evidence supports the notion that neuroinflammation plays a critical role in etiology of major depressive disorder (MDD), at least subset patients. By virtue their capacity to transform into reactive states response inflammatory insults, microglia, brain’s resident immune cells, play pivotal induction neuroinflammation. Experimental studies have demonstrated ability microglia recognize pathogens or damaged leading activation cytotoxic exacerbates damage brain cells. However, display wide range responses injury and may also promote resolution stages inflammation tissue regeneration. MDD has been associated with chronic priming microglia. Recent suggest altered microglial morphology function, caused either by intense senescence, contribute depression impairments neuroplasticity. In this context, modifying phenotype tuning pathways might important translational relevance harness MDD. Interestingly, it was recently shown different phenotypes are distinct metabolic analysis underlying molecular mechanisms points an instrumental for energy metabolism shaping functions. Here, we review various canonical pro-inflammatory, anti-inflammatory provide new therapeutic opportunities control disorders, strong focus on

Language: Английский

Citations

48
Loss of microglial MCT4 leads to defective synaptic pruning and anxiety-like behavior in mice DOI Creative Commons
Katia Monsorno,

Kyllian Ginggen,

Andranik Ivanov

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Sept. 16, 2023

Microglia, the innate immune cells of central nervous system, actively participate in brain development by supporting neuronal maturation and refining synaptic connections. These are emerging as highly metabolically flexible, able to oxidize different energetic substrates meet their energy demand. Lactate is particularly abundant brain, but whether microglia use it a metabolic fuel has been poorly explored. Here we show that can import lactate, this coupled with increased lysosomal acidification. In vitro, loss monocarboxylate transporter MCT4 prevents lactate-induced modulation leads defective cargo degradation. Microglial depletion vivo impaired pruning, associated excitation hippocampal neurons, enhanced AMPA/GABA ratio, vulnerability seizures anxiety-like phenotype. Overall, these findings selective disruption sufficient alter synapse refinement induce defects mouse adult behavior.

Language: Английский

Citations

30
Microglia in Health and Diseases: Integrative Hubs of the Central Nervous System (CNS) DOI
Amanda Sierra, Véronique E. Miron, Rosa Chiara Paolicelli

et al.

Cold Spring Harbor Perspectives in Biology, Journal Year: 2024, Volume and Issue: 16(8), P. a041366 - a041366

Published: March 4, 2024

Amanda Sierra1,2,3, Veronique E. Miron4,5,6, Rosa C. Paolicelli7 and Richard M. Ransohoff8 1Achucarro Basque Center for Neuroscience, Glial Cell Biology Laboratory, Science Park of UPV/EHU, E-48940 Leioa, Bizkaia, Spain 2Department Biochemistry Molecular Biology, University the Country EHU/UPV, 48940 3Ikerbasque Foundation, Bilbao 48009, 4BARLO Multiple Sclerosis Centre, Keenan Research Centre Biomedical at St. Michael's Hospital, Toronto M5B 1T8, Canada 5Department Immunology, Toronto, M5S 1A8, 6UK Dementia Institute Edinburgh, Edinburgh BioQuarter, EH16 4TJ, United Kingdom 7Department Sciences, Faculty Medicine, Lausanne, CH-1005 Switzerland 8Third Rock Ventures, Boston, Massachusetts 02215, USA Correspondence: amanda.sierra{at}achucarro.org; rransohoff{at}thirdrockventures.com

Language: Английский

Citations

15
The ins and outs of microglial cells in brain health and disease DOI Creative Commons

Carla Pallarés-Moratalla,

Gabriele Bergers

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: April 11, 2024

Microglia are the brain’s resident macrophages that play pivotal roles in immune surveillance and maintaining homeostasis of Central Nervous System (CNS). functionally implicated various cerebrovascular diseases, including stroke, aneurysm, tumorigenesis as they regulate neuroinflammatory responses tissue repair processes. Here, we review manifold functions microglia brain under physiological pathological conditions, primarily focusing on implication glioma propagation progression. We further current status therapies targeting microglial cells, their re-education, depletion, re-population approaches therapeutic options to improve patient outcomes for neurological disorders, cancer.

Language: Английский

Citations

11
Early precursor-derived pituitary gland tissue-resident macrophages play a pivotal role in modulating hormonal balance DOI

Henna Lehtonen,

Heli Jokela, Julian Hofmann

et al.

Cell Reports, Journal Year: 2025, Volume and Issue: 44(2), P. 115227 - 115227

Published: Jan. 21, 2025

Language: Английский

Citations

1