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JOURNAL ARTICLE
Qiu-Qin Han, Shi-Yu Shen, Ling-Feng Liang, Xiao-Rong Chen, Jin Yu
BACKGROUND: Both functional brain imaging studies and autopsy reports have indicated the presence of synaptic loss in the brains of depressed patients. The activated microglia may dysfunctionally engulf neuronal synapses, leading to synaptic loss and behavioral impairments in depression. However, the mechanisms of microglial-synaptic interaction under depressive conditions remain unclear. METHODS: We utilized lipopolysaccharide (LPS) to induce a mouse model of depression, examining the effects of LPS on behaviors, synapses, microglia, microglial phagocytosis of synapses, and the C1q/C3-CR3 complement signaling pathway...
April 18, 2024: Brain, Behavior, and Immunity
#2
REVIEW
Laura Airas, Robert A Bermel, Tanuja Chitnis, Hans-Peter Hartung, Jin Nakahara, Olaf Stuve, Mitzi J Williams, Bernd C Kieseier, Heinz Wiendl
Bruton's tyrosine kinase (BTK) inhibitors are an emerging class of therapeutics in multiple sclerosis (MS). BTK is expressed in B-cells and myeloid cells, key progenitors of which include dendritic cells, microglia and macrophages, integral effectors of MS pathogenesis, along with mast cells, establishing the relevance of BTK inhibitors to diverse autoimmune conditions. First-generation BTK inhibitors are currently utilized in the treatment of B-cell malignancies and show efficacy in B-cell modulation. B-cell depleting therapies have shown success as disease-modifying treatments (DMTs) in MS, highlighting the potential of BTK inhibitors for this indication; however, first-generation BTK inhibitors exhibit a challenging safety profile that is unsuitable for chronic use, as required for MS DMTs...
2024: Therapeutic Advances in Neurological Disorders
#3
JOURNAL ARTICLE
Audrey R Fetsko, Dylan J Sebo, Lilyana B Budzynski, Alli Scharbarth, Michael R Taylor
During neuroinflammation, the proinflammatory cytokine interleukin-1β (IL-1β) impacts blood-brain barrier (BBB) function by disrupting brain endothelial tight junctions, promoting vascular permeability, and increasing transmigration of immune cells. Here, we examined the effects of Il-1β on the in vivo initiation of BBB development. We generated doxycycline-inducible transgenic zebrafish to secrete Il-1β in the CNS. To validate the utility of our model, we showed Il-1β dose-dependent mortality, recruitment of neutrophils, and expansion of microglia...
May 17, 2024: IScience
#4
JOURNAL ARTICLE
Xiaozhu Hao, Luyi Lin, Chengfeng Sun, Chanchan Li, Jing Wang, Min Jiang, Zhenwei Yao, Yanmei Yang
BACKGROUND: Notch1 signaling inhibiton with N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycine t-butylester] (DAPT) treatment could promote brain recovery and the intervention effect is different between striatum (STR) and cortex (CTX), which might be accounted for different changes of glial activities, but the in-depth mechanism is still unknown. The purpose of this study was to identify whether DAPT could modulate microglial subtype shifts and astroglial-endfeet aquaporin-4 (AQP4) mediated waste solute drainage...
April 17, 2024: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
#5
JOURNAL ARTICLE
Naomi Kouri, Isabelle Frankenhauser, Zhongwei Peng, Sydney A Labuzan, Baayla D C Boon, Christina M Moloney, Cyril Pottier, Daniel P Wickland, Kelsey Caetano-Anolles, Nick Corriveau-Lecavalier, Jessica F Tranovich, Ashley C Wood, Kelly M Hinkle, Sarah J Lincoln, A J Spychalla, Matthew L Senjem, Scott A Przybelski, Erica Engelberg-Cook, Christopher G Schwarz, Rain S Kwan, Elizabeth R Lesser, Julia E Crook, Rickey E Carter, Owen A Ross, Christian Lachner, Nilüfer Ertekin-Taner, Tanis J Ferman, Julie A Fields, Mary M Machulda, Vijay K Ramanan, Aivi T Nguyen, R Ross Reichard, David T Jones, Jonathan Graff-Radford, Bradley F Boeve, David S Knopman, Ronald C Petersen, Clifford R Jack, Kejal Kantarci, Gregory S Day, Ranjan Duara, Neill R Graff-Radford, Dennis W Dickson, Val J Lowe, Prashanthi Vemuri, Melissa E Murray
IMPORTANCE: Factors associated with clinical heterogeneity in Alzheimer disease (AD) lay along a continuum hypothesized to associate with tangle distribution and are relevant for understanding glial activation considerations in therapeutic advancement. OBJECTIVES: To examine clinicopathologic and neuroimaging characteristics of disease heterogeneity in AD along a quantitative continuum using the corticolimbic index (CLix) to account for individuality of spatially distributed tangles found at autopsy...
April 15, 2024: JAMA Neurology
#6
Jennifer N Harmon, Preeja Chandran, Abarajithan Chandrasekaran, Jeffrey E Hyde, Gustavo J Hernandez, May J Reed, Matthew F Bruce, Zin Z Khaing
Normal aging is associated with significant deleterious cerebrovascular changes; these have been implicated in disease pathogenesis and increased susceptibility to ischemic injury. While these changes are well documented in the brain, few studies have been conducted in the spinal cord. Here, we utilize specialized contrast-enhanced ultrasound (CEUS) imaging to investigate age-related changes in cervical spinal vascular anatomy and hemodynamics in male Fisher 344 rats, a common strain in aging research. Aged rats (24-26 mo...
March 14, 2024: bioRxiv
#7
Hyehyun Kim, Bryan Le, Noah Goshi, Kan Zhu, Ana Cristina Grodzki, Pamela J Lein, Min Zhao, Erkin Seker
INTRODUCTION: The etiology and progression of sporadic Alzheimer's Disease (AD) have been studied for decades. One proposed mechanism is that amyloid-beta (Aβ) proteins induce neuroinflammation, synapse loss, and neuronal cell death. Microglia play an especially important role in Aβ clearance, and alterations in microglial function due to aging or disease may result in Aβ accumulation and deleterious effects on neuronal function. However, studying these complex factors in vivo , where numerous confounding processes exist, is challenging, and until recently, in vitro models have not allowed sustained culture of microglia, astrocytes and neurons in the same culture...
March 17, 2024: bioRxiv
#8
Glenna J Wallis, Laura A Bell, John N Wagner, Lauren Buxton, Lakshmini Balachandar, Karen S Wilcox
Microglia are highly adaptable innate immune cells that rapidly respond to damage signals in the brain through adoption of a reactive phenotype and production of defensive inflammatory cytokines. Microglia express a distinct transcriptome, encoding receptors that allow them to dynamically respond to pathogens, damage signals, and cellular debris. Expression of one such receptor, the microglia-specific purinergic receptor P2ry12 , is known to be downregulated in reactive microglia. Here, we explore the microglial response to purinergic damage signals in reactive microglia in the TMEV mouse model of viral brain infection and temporal lobe epilepsy...
March 12, 2024: bioRxiv
#9
REVIEW
Sepideh Parsi, Cindy Zhu, Negin Jalali Motlagh, Daeki Kim, Enrico G Küllenberg, Hyung-Hwan Kim, Rebecca L Gillani, John W Chen
Neuroinflammation is a key immune response observed in many neurologic diseases. Although an appropriate immune response can be beneficial, aberrant activation of this response recruits excessive proinflammatory cells to cause damage. Because the central nervous system is separated from the periphery by the blood-brain barrier (BBB) that creates an immune-privileged site, it has its own unique immune cells and immune response. Moreover, neuroinflammation can compromise the BBB causing an influx of peripheral immune cells and factors...
May 2024: Magnetic Resonance Imaging Clinics of North America
#10
JOURNAL ARTICLE
Timothy J Y Birkle, Henriette M G Willems, John Skidmore, Guy C Brown
Neuropathology is often mediated by interactions between neurons and glia that cannot be modeled by monocultures. However, cocultures are difficult to use and analyze for high-content screening. Here, we perform compound screening using primary neuron-glia cultures to model inflammatory neurodegeneration, live-cell stains, and automated classification of neurons, astrocytes or microglia using open-source software. Out of 227 compounds with known bioactivities, 29 protected against lipopolysaccharide-induced neuronal loss, including drugs affecting adrenergic, steroid, inflammatory and MAP kinase signaling...
April 19, 2024: IScience
#11
JOURNAL ARTICLE
Pegah Haghighi, Mandee K Schaub, Adam H Shebindu, Gayathri Vijayakumar, Armaan Sood, Rafael Granja-Vazquez, Sourav S Patnaik, Caroline N Jones, Gregory O Dussor, Joseph J Pancrazio
PIEZO1 is a mechanosensitive ion channel expressed in various organs, including but not limited to the brain, heart, lungs, kidneys, bone, and skin. PIEZO1 has been implicated in astrocyte, microglia, capillary, and oligodendrocyte signaling in the mammalian cortex. Using murine embryonic frontal cortex tissue, we examined the protein expression and functionality of PIEZO1 channels in cultured networks leveraging substrate-integrated microelectrode arrays (MEAs) with additional quantitative results from calcium imaging and whole-cell patch-clamp electrophysiology...
February 27, 2024: Brain Sciences
#12
JOURNAL ARTICLE
Amy A Jolly, Robin B Brown, Daniel J Tozer, Young T Hong, Tim D Fryer, Franklin Aigbirhio, John O'brien, Hugh S Markus
BACKGROUND: Fatigue is a common symptom in cerebral small vessel disease (SVD), but its pathogenesis is poorly understood. It has been suggested that inflammation may play a role. We determined whether central (neuro) inflammation and peripheral inflammation were associated with fatigue in SVD. METHODS: 36 patients with moderate to severe SVD underwent neuropsychometric testing, combined PET-MRI and blood draw for analysis of inflammatory blood biomarkers. Microglial signal was taken as a proxy for neuroinflammation, assessed with radioligand 11C-PK11195...
March 27, 2024: International Journal of Stroke: Official Journal of the International Stroke Society
#13
JOURNAL ARTICLE
Patricia Martínez-Tazo, Alexandra Santos, Mohamed Kotb Selim, Elena Espinós-Soler, Silvia De Santis
Overcoming sex bias in preclinical research requires not only including animals of both sexes in the experiments, but also developing proper tools to handle such data. Recent work revealed sensitivity of diffusion-weighted MRI to glia morphological changes in response to inflammatory stimuli, opening up exciting possibilities to characterize inflammation in a variety of preclinical models of pathologies, the great majority of them available in mice. However, there are limited resources dedicated to mouse imaging, like those required for the data processing and analysis...
March 21, 2024: NeuroImage
#14
JOURNAL ARTICLE
Vanessa I Francis, Corin Liddle, Emma Camacho, Madhura Kulkarni, Samuel R S Junior, Jamie A Harvey, Elizabeth R Ballou, Darren D Thomson, Gordon D Brown, J Marie Hardwick, Arturo Casadevall, Jonathan Witton, Carolina Coelho
Cryptococcus neoformans causes lethal meningitis and accounts for approximately 10%-15% of AIDS-associated deaths worldwide. There are major gaps in our understanding of how this fungus invades the mammalian brain. To investigate the dynamics of C. neoformans tissue invasion, we mapped fungal localization and host cell interactions in infected brain, lung, and upper airways using mouse models of systemic and airway infection. To enable this, we developed an in situ imaging pipeline capable of measuring large volumes of tissue while preserving anatomical and cellular information by combining thick tissue sections, tissue clarification, and confocal imaging...
March 21, 2024: MBio
#15
JOURNAL ARTICLE
Nynke A Vepřek, Madeline H Cooper, Laura Laprell, Emily Jie-Ning Yang, Sander Folkerts, Ruiyang Bao, Malgorzata Boczkowska, Nicholas J Palmer, Roberto Dominguez, Thomas G Oertner, Liza A Pon, J Bradley Zuchero, Dirk H Trauner
Actin is one of the most abundant proteins in eukaryotic cells and is a key component of the cytoskeleton. A range of small molecules has emerged that interfere with actin dynamics by either binding to polymeric F-actin or monomeric G-actin to stabilize or destabilize filaments or prevent their formation and growth, respectively. Among these, the latrunculins, which bind to G-actin and affect polymerization, are widely used as tools to investigate actin-dependent cellular processes. Here, we report a photoswitchable version of latrunculin, termed opto-latrunculin ( OptoLat ), which binds to G-actin in a light-dependent fashion and affords optical control over actin polymerization...
March 21, 2024: Journal of the American Chemical Society
#16
JOURNAL ARTICLE
Qianru Yang, Alberto L Vazquez, X Tracy Cui
Cerebral microbleeds (CMBs) are associated with higher risk for various neurological diseases including stroke, dementia, and Alzheimer's disease. However, the understanding of cellular pathology of CMBs, particularly in deep brain regions, remains limited. Utilizing two-photon microscopy and microprism implantation, we longitudinally imaged the impact of CMBs on neuronal and microglial activities across cortical depths in awake mice. A temporary decline in spontaneous neuronal activity occurred throughout cortical layers, followed by recovery within a week...
April 19, 2024: IScience
#17
REVIEW
Sophia-Marie Hartmann, Johanna Heider, Richard Wüst, Andreas J Fallgatter, Hansjürgen Volkmer
Multiple lines of evidence implicate increased neuroinflammation mediated by glial cells to play a key role in neurodevelopmental disorders such as schizophrenia. Microglia, which are the primary innate immune cells of the brain, are crucial for the refinement of the synaptic circuitry during early brain development by synaptic pruning and the regulation of synaptic plasticity during adulthood. Schizophrenia risk factors as genetics or environmental influences may further be linked to increased activation of microglia, an increase of pro-inflammatory cytokine levels and activation of the inflammasome resulting in an overall elevated neuroinflammatory state in patients...
2024: Frontiers in Cellular Neuroscience
#18
JOURNAL ARTICLE
Faye McLeod, Elaine McDermott, Shermin Mak, Darren Walsh, Mark Turnbull, Fiona E N LeBeau, Andrew Jackson, Andrew J Trevelyan, Gavin J Clowry
INTRODUCTION: Expression of light sensitive ion channels by selected neurons has been achieved by viral mediated transduction with gene constructs, but for this to have therapeutic uses, for instance in treating epilepsy, any adverse effects of viral infection on the cerebral cortex needs to be evaluated. Here, we assessed the impact of adeno-associated virus 8 (AAV8) carrying DNA code for a soma targeting light activated chloride channel/FusionRed (FR) construct under the CKIIa promoter...
2024: Frontiers in Neuroscience
#19
JOURNAL ARTICLE
Daniëlle C Voshart, Myrthe Klaver, Yuting Jiang, Hilmar R J van Weering, Fleur van Buuren-Broek, Gideon P van der Linden, Davide Cinat, Harry H Kiewiet, Justin Malimban, Daniel A Vazquez-Matias, Luiza Reali Nazario, Ayla C Scholma, Jeffrey Sewdihal, Marc-Jan van Goethem, Peter van Luijk, Rob P Coppes, Lara Barazzuol
BACKGROUND AND PURPOSE: Although proton therapy is increasingly being used in the treatment of paediatric and adult brain tumours, there are still uncertainties surrounding the biological effect of protons on the normal brain. Microglia, the brain-resident macrophages, have been shown to play a role in the development of radiation-induced neurotoxicity. However, their molecular and hence functional response to proton irradiation remains unknown. This study investigates the effect of protons on microglia by comparing the effect of photons and protons as well as the influence of age and different irradiated volumes...
March 1, 2024: Radiotherapy and Oncology
#20
JOURNAL ARTICLE
Obada M Alzghool, Richard Aarnio, Jatta S Helin, Saara Wahlroos, Thomas Keller, Markus Matilainen, Junel Solis, Jonathan J Danon, Michael Kassiou, Anniina Snellman, Olof Solin, Juha O Rinne, Merja Haaparanta-Solin
BACKGROUND: P2X7 receptor has emerged as a potentially superior PET imaging marker to TSPO, the gold standard for imaging glial reactivity. [11 C]SMW139 is the most recently developed radiotracer to image P2X7 receptor. The aim of this study was to image reactive glia in the APP/PS1-21 transgenic (TG) mouse model of Aβ deposition longitudinally using [11 C]SMW139 targeting P2X7 receptor and to compare tracer uptake to that of [18 F]F-DPA targeting TSPO at the final imaging time point...
March 6, 2024: EJNMMI Research
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