journal
https://read.qxmd.com/read/38771121/activation-of-shh-smo-is-sufficient-to-maintain-oligodendrocyte-precursor-cells-in-an-undifferentiated-state-and-is-not-necessary-for-myelin-formation-and-re-myelination
#1
JOURNAL ARTICLE
Sonia Nocera, Miguel A Marchena, Beatriz Fernández-Gómez, Paula Gómez-Martín, Estefanía Sánchez-Jiménez, Alba Macías-Castellano, Yolanda Laó, Christian Cordano, Óscar Gómez-Torres, Rafael Luján, Fernando de Castro
Myelination is the terminal step in a complex and precisely timed program that orchestrates the proliferation, migration and differentiation of oligodendroglial cells. It is thought that Sonic Hedgehog (Shh) acting on Smoothened (Smo) participates in regulating this process, but that these effects are highly context dependent. Here, we investigate oligodendroglial development and remyelination from three specific transgenic lines: NG2-CreERT2 (control), Smofl/fl /NG2-CreERT2 (loss of function), and SmoM2/NG2-CreERT2 (gain of function), as well as pharmacological manipulation that enhance or inhibit the Smo pathway (Smoothened Agonist (SAG) or cyclopamine treatment, respectively)...
May 21, 2024: Glia
https://read.qxmd.com/read/38629411/astrocytic-uptake-of-posttranslationally-modified-amyloid-%C3%AE-leads-to-endolysosomal-system-disruption-and-induction-of-pro-inflammatory-signaling
#2
JOURNAL ARTICLE
Sarah Wirth, Annika Schlößer, Antonia Beiersdorfer, Michaela Schweizer, Marcel S Woo, Manuel A Friese, Christian Lohr, Katarzyna M Grochowska
The disruption of astrocytic catabolic processes contributes to the impairment of amyloid-β (Aβ) clearance, neuroinflammatory signaling, and the loss of synaptic contacts in late-onset Alzheimer's disease (AD). While it is known that the posttranslational modifications of Aβ have significant implications on biophysical properties of the peptides, their consequences for clearance impairment are not well understood. It was previously shown that N-terminally pyroglutamylated Aβ3(pE)-42, a significant constituent of amyloid plaques, is efficiently taken up by astrocytes, leading to the release of pro-inflammatory cytokine tumor necrosis factor α and synapse loss...
April 17, 2024: Glia
https://read.qxmd.com/read/38613395/transcription-factor-olig2-is-a-major-downstream-effector-of-histone-demethylase-phf8-during-oligodendroglial-development
#3
JOURNAL ARTICLE
Marco Kremp, Tim Aberle, Elisabeth Sock, Bettina Bohl, Simone Hillgärtner, Jürgen Winkler, Michael Wegner
The plant homeodomain finger protein Phf8 is a histone demethylase implicated by mutation in mice and humans in neural crest defects and neurodevelopmental disturbances. Considering its widespread expression in cell types of the central nervous system, we set out to determine the role of Phf8 in oligodendroglial cells to clarify whether oligodendroglial defects are a possible contributing factor to Phf8-dependent neurodevelopmental disorders. Using loss- and gain-of-function approaches in oligodendroglial cell lines and primary cell cultures, we show that Phf8 promotes the proliferation of rodent oligodendrocyte progenitor cells and impairs their differentiation to oligodendrocytes...
April 13, 2024: Glia
https://read.qxmd.com/read/38597386/low-grade-systemic-inflammation-stimulates-microglial-turnover-and-accelerates-the-onset-of-alzheimer-s-like-pathology
#4
JOURNAL ARTICLE
Monica Guerrero-Carrasco, Imogen Targett, Adrian Olmos-Alonso, Mariana Vargas-Caballero, Diego Gomez-Nicola
Several in vivo studies have shown that systemic inflammation, mimicked by LPS, triggers an inflammatory response in the CNS, driven by microglia, characterized by an increase in inflammatory cytokines and associated sickness behavior. However, most studies induce relatively high systemic inflammation, not directly compared with the more common low-grade inflammatory events experienced in humans during the life course. Using mice, we investigated the effects of low-grade systemic inflammation during an otherwise healthy early life, and how this may precondition the onset and severity of Alzheimer's disease (AD)-like pathology...
April 10, 2024: Glia
https://read.qxmd.com/read/38591338/sexually-dimorphic-effects-of-pexidartinib-on-nerve-injury-induced-neuropathic-pain-in-mice
#5
JOURNAL ARTICLE
Fumihiro Saika, Yohji Fukazawa, Yu Hatano, Shiroh Kishioka, Yuko Hino, Shinjiro Hino, Kentaro Suzuki, Norikazu Kiguchi
It is well-established that spinal microglia and peripheral macrophages play critical roles in the etiology of neuropathic pain; however, growing evidence suggests sex differences in pain hypersensitivity owing to microglia and macrophages. Therefore, it is crucial to understand sex- and androgen-dependent characteristics of pain-related myeloid cells in mice with nerve injury-induced neuropathic pain. To deplete microglia and macrophages, pexidartinib (PLX3397), an inhibitor of the colony-stimulating factor 1 receptor, was orally administered, and mice were subjected to partial sciatic nerve ligation (PSL)...
April 9, 2024: Glia
https://read.qxmd.com/read/38591270/morphological-and-electrophysiological-characterization-of-a-novel-displaced-astrocyte-in-the-mouse-retina
#6
JOURNAL ARTICLE
Joseph Matthew Holden, Lauren Katie Wareham, David John Calkins
Astrocytes throughout the central nervous system are heterogeneous in both structure and function. This diversity leads to tissue-specific specialization where morphology is adapted to the surrounding neuronal circuitry, as seen in Bergman glia of the cerebellum and Müller glia of the retina. Because morphology can be a differentiating factor for cellular classification, we recently developed a mouse where glial-fibrillary acidic protein (GFAP)-expressing cells stochastically label for full membranous morphology...
April 9, 2024: Glia
https://read.qxmd.com/read/38591259/astrocyte-switch-to-the-hyperactive-mode
#7
JOURNAL ARTICLE
Shun Araki, Ichinosuke Onishi, Yoko Ikoma, Ko Matsui
Increasing pieces of evidence have suggested that astrocyte function has a strong influence on neuronal activity and plasticity, both in physiological and pathophysiological situations. In epilepsy, astrocytes have been shown to respond to epileptic neuronal seizures; however, whether they can act as a trigger for seizures has not been determined. Here, using the copper implantation method, spontaneous neuronal hyperactivity episodes were reliably induced during the week following implantation. With near 24-h continuous recording for over 1 week of the local field potential with in vivo electrophysiology and astrocyte cytosolic Ca2+ with the fiber photometry method, spontaneous occurrences of seizure episodes were captured...
April 9, 2024: Glia
https://read.qxmd.com/read/38587137/oligodendrocyte-selective-deletion-of-the-eif2%C3%AE-kinase-perk-eif2ak3-limits-functional-recovery-after-spinal-cord-injury
#8
JOURNAL ARTICLE
Sujata Saraswat Ohri, Michael D Forston, Scott A Myers, Brandon L Brown, Kariena R Andres, Russell M Howard, Yonglin Gao, Yu Liu, Douglas R Cavener, Michal Hetman, Scott R Whittemore
After spinal cord injury (SCI), re-establishing cellular homeostasis is critical to optimize functional recovery. Central to that response is PERK signaling, which ultimately initiates a pro-apoptotic response if cellular homeostasis cannot be restored. Oligodendrocyte (OL) loss and white matter damage drive functional consequences and determine recovery potential after thoracic contusive SCI. We examined acute (<48 h post-SCI) and chronic (6 weeks post-SCI) effects of conditionally deleting Perk from OLs prior to SCI...
April 8, 2024: Glia
https://read.qxmd.com/read/38587131/downregulated-expression-of-lactate-dehydrogenase-in-adult-oligodendrocytes-and-its-implication-for-the-transfer-of-glycolysis-products-to-axons
#9
JOURNAL ARTICLE
Erik Späte, Baoyu Zhou, Ting Sun, Kathrin Kusch, Ebrahim Asadollahi, Sophie B Siems, Constanze Depp, Hauke B Werner, Gesine Saher, Johannes Hirrlinger, Wiebke Möbius, Klaus-Armin Nave, Sandra Goebbels
Oligodendrocytes and astrocytes are metabolically coupled to neuronal compartments. Pyruvate and lactate can shuttle between glial cells and axons via monocarboxylate transporters. However, lactate can only be synthesized or used in metabolic reactions with the help of lactate dehydrogenase (LDH), a tetramer of LDHA and LDHB subunits in varying compositions. Here we show that mice with a cell type-specific disruption of both Ldha and Ldhb genes in oligodendrocytes lack a pathological phenotype that would be indicative of oligodendroglial dysfunctions or lack of axonal metabolic support...
April 8, 2024: Glia
https://read.qxmd.com/read/38577970/chronically-activated-microglia-in-als-gradually-lose-their-immune-functions-and-develop-unconventional-proteome
#10
JOURNAL ARTICLE
Romina Barreto-Núñez, Louis-Charles Béland, Hejer Boutej, Vincent Picher-Martel, Nicolas Dupré, Luis Barbeito, Jasna Kriz
Neuroinflammation and chronic activation of microglial cells are the prominent features of amyotrophic lateral sclerosis (ALS) pathology. While alterations in the mRNA profile of diseased microglia have been well documented, the actual microglia proteome remains poorly characterized. Here we performed a functional characterization together with proteome analyses of microglial cells at different stages of disease in the SOD1-G93A model of ALS. Functional analyses of microglia derived from the lumbar spinal cord of symptomatic mice revealed: (i) remarkably high mitotic index (close to 100% cells are Ki67+) (ii) significant decrease in phagocytic capacity when compared to age-matched control microglia, and (iii) diminished response to innate immune challenges in vitro and in vivo...
April 5, 2024: Glia
https://read.qxmd.com/read/38572807/the-therapeutic-effect-of-gas6-in-remyelination-is-dependent-upon-tyro3
#11
JOURNAL ARTICLE
Negar Asadian, Andrea Aprico, Moore Chen, Daniel Yuen, Angus P R Johnston, Trevor J Kilpatrick, Michele D Binder
Multiple sclerosis is an autoimmune disease of the central nervous system (CNS) characterized by demyelination, axonal damage and, for the majority of people, a decline in neurological function in the long-term. Remyelination could assist in the protection of axons and their functional recovery, but such therapies are not, as yet, available. The TAM (Tyro3, Axl, and MERTK) receptor ligand GAS6 potentiates myelination in vitro and promotes recovery in pre-clinical models of MS. However, it has remained unclear which TAM receptor is responsible for transducing this effect and whether post-translational modification of GAS6 is required...
April 4, 2024: Glia
https://read.qxmd.com/read/38546197/the-myelination-associated-g-protein-coupled-receptor-37-is-regulated-by-zfp488-nkx2-2-and-sox10-during-oligodendrocyte-differentiation
#12
JOURNAL ARTICLE
Antonia L Schmidt, Marco Kremp, Takaaki Aratake, Siying Cui, Yifeng Lin, Xiaowen Zhong, Q Richard Lu, Chengfu Zhang, Mengsheng Qiu, Tim Aberle, Michael Wegner
Oligodendrocyte differentiation and myelination in the central nervous system are controlled and coordinated by a complex gene regulatory network that contains several transcription factors, including Zfp488 and Nkx2.2. Despite the proven role in oligodendrocyte differentiation little is known about the exact mode of Zfp488 and Nkx2.2 action, including their target genes. Here, we used overexpression of Zfp488 and Nkx2.2 in differentiating CG4 cells to identify aspects of the oligodendroglial expression profile that depend on these transcription factors...
March 28, 2024: Glia
https://read.qxmd.com/read/38515287/id-factors-regulate-the-ability-of-m%C3%A3-ller-glia-to-become-proliferating-neurogenic-progenitor-like-cells
#13
JOURNAL ARTICLE
Olivia B Taylor, Snehal P Patel, Evan C Hawthorn, Heithem M El-Hodiri, Andy J Fischer
The purpose of this study was to investigate how ID factors regulate the ability of Müller glia (MG) to reprogram into proliferating MG-derived progenitor cells (MGPCs) in the chick retina. We found that ID1 is transiently expressed by maturing MG (mMG), whereas ID4 is maintained in mMG in embryonic retinas. In mature retinas, ID4 was prominently expressed by resting MG, but following retinal damage ID4 was rapidly upregulated and then downregulated in MGPCs. By contrast, ID1, ID2, and ID3 were low in resting MG and then upregulated in MGPCs...
March 21, 2024: Glia
https://read.qxmd.com/read/38515286/tamoxifen-exerts-direct-and-microglia-mediated-effects-preventing-neuroinflammatory-changes-in-the-adult-mouse-hippocampal-neurogenic-niche
#14
JOURNAL ARTICLE
Isabella Crisci, Sara Bonzano, Zinter Nicolas, Eleonora Dallorto, Paolo Peretto, Wojciech Krezel, Silvia De Marchis
Tamoxifen-inducible systems are widely used in research to control Cre-mediated gene deletion in genetically modified animals. Beyond Cre activation, tamoxifen also exerts off-target effects, whose consequences are still poorly addressed. Here, we investigated the impact of tamoxifen on lipopolysaccharide (LPS)-induced neuroinflammatory responses, focusing on the neurogenic activity in the adult mouse dentate gyrus. We demonstrated that a four-day LPS treatment led to an increase in microglia, astrocytes and radial glial cells with concomitant reduction of newborn neurons...
March 21, 2024: Glia
https://read.qxmd.com/read/38511347/an-early-enriched-experience-drives-targeted-microglial-engulfment-of-miswired-neural-circuitry-during-a-restricted-postnatal-period
#15
JOURNAL ARTICLE
Lara Rogerson-Wood, Claire S Goldsbury, Atomu Sawatari, Catherine A Leamey
Brain function is critically dependent on correct circuit assembly. Microglia are well-known for their important roles in immunological defense and neural plasticity, but whether they can also mediate experience-induced correction of miswired circuitry is unclear. Ten-m3 knockout (KO) mice display a pronounced and stereotyped visuotopic mismapping of ipsilateral retinal inputs in their visual thalamus, providing a useful model to probe circuit correction mechanisms. Environmental enrichment (EE) commenced around birth, but not later in life, can drive a partial correction of the most mismapped retinal inputs in Ten-m3 KO mice...
March 21, 2024: Glia
https://read.qxmd.com/read/38506330/spatial-organization-of-astrocyte-clones-the-role-of-developmental-progenitor-timing
#16
JOURNAL ARTICLE
Ana Cristina Ojalvo-Sanz, Carolina Pernia-Solanilla, Laura López-Mascaraque
Astrocytes represent a diverse and morphologically complex group of glial cells critical for shaping and maintaining nervous system homeostasis, as well as responding to injuries. Understanding the origins of astroglial heterogeneity, originated from a limited number of progenitors, has been the focus of many studies. Most of these investigations have centered on protoplasmic and pial astrocytes, while the clonal relationship of fibrous astrocytes or juxtavascular astrocytes has remained relatively unexplored...
March 20, 2024: Glia
https://read.qxmd.com/read/38497409/the-use-of-a-sox10-reporter-toward-ameliorating-oligodendrocyte-lineage-differentiation-from-human-induced-pluripotent-stem-cells
#17
JOURNAL ARTICLE
Valerio E C Piscopo, Alexandra Chapleau, Gabriela J Blaszczyk, Julien Sirois, Zhipeng You, Vincent Soubannier, Carol X-Q Chen, Geneviève Bernard, Jack P Antel, Thomas M Durcan
Oligodendrocytes (OLs) are key players in the central nervous system, critical for the formation and maintenance of the myelin sheaths insulating axons, ensuring efficient neuronal communication. In the last decade, the use of human induced pluripotent stem cells (iPSCs) has become essential for recapitulating and understanding the differentiation and role of OLs in vitro. Current methods include overexpression of transcription factors for rapid OL generation, neglecting the complexity of OL lineage development...
March 18, 2024: Glia
https://read.qxmd.com/read/38497356/er-stress-response-in-retinal-m%C3%A3-ller-glia-occurs-significantly-earlier-than-amyloid-pathology-in-the-alzheimer-s-mouse-brain-and-retina
#18
JOURNAL ARTICLE
Sarah I Palko, Marc R Benoit, Annie Y Yao, Royce Mohan, Riqiang Yan
Alzheimer's Disease (AD) pathogenesis is thought to begin up to 20 years before cognitive symptoms appear, suggesting the need for more sensitive diagnostic biomarkers of AD. In this report, we demonstrated pathological changes in retinal Müller glia significantly earlier than amyloid pathology in AD mouse models. By utilizing the knock-in NLGF mouse model, we surprisingly discovered an increase in reticulon 3 (RTN3) protein levels in the NLGF retina as early as postnatal day 30 (P30). Despite RTN3 being a canonically neuronal protein, this increase was noted in the retinal Müller glia, confirmed by immunohistochemical characterization...
March 18, 2024: Glia
https://read.qxmd.com/read/38482984/adenosine-receptors-are-the-on-and-off-switch-of-astrocytic-cannabinoid-type-1-cb1-receptor-effect-upon-synaptic-plasticity-in-the-medial-prefrontal-cortex
#19
JOURNAL ARTICLE
Joana Gonçalves-Ribeiro, Oksana K Savchak, Sara Costa-Pinto, Joana I Gomes, Rafael Rivas-Santisteban, Alejandro Lillo, Javier Sánchez Romero, Ana M Sebastião, Marta Navarrete, Gemma Navarro, Rafael Franco, Sandra H Vaz
The medial prefrontal cortex (mPFC) is involved in cognitive functions such as working memory. Astrocytic cannabinoid type 1 receptor (CB1R) induces cytosolic calcium (Ca2+ ) concentration changes with an impact on neuronal function. mPFC astrocytes also express adenosine A1 and A2A receptors (A1 R, A2A R), being unknown the crosstalk between CB1R and adenosine receptors in these cells. We show here that a further level of regulation of astrocyte Ca2+ signaling occurs through CB1R-A2A R or CB1R-A1 R heteromers that ultimately impact mPFC synaptic plasticity...
March 14, 2024: Glia
https://read.qxmd.com/read/38482950/upregulation-of-the-secretory-pathway-ca-2-mn-2-atpase-isoform-1-in-lps-stimulated-microglia-and-its-involvement-in-mn-2-induced-golgi-fragmentation
#20
JOURNAL ARTICLE
Aysha M Bhojwani-Cabrera, Alicia Bautista-García, Veronika E Neubrand, Francisco A Membrive-Jiménez, Mattia Bramini, David Martin-Oliva, Miguel A Cuadros, José Luis Marín-Teva, Julio Navascués, Peter Vangheluwe, M Rosario Sepúlveda
Microglia play an important protective role in the healthy nervous tissue, being able to react to a variety of stimuli that induce different intracellular cascades for specific tasks. Ca2+ signaling can modulate these pathways, and we recently reported that microglial functions depend on the endoplasmic reticulum as a Ca2+ store, which involves the Ca2+ transporter SERCA2b. Here, we investigated whether microglial functions may also rely on the Golgi, another intracellular Ca2+ store that depends on the secretory pathway Ca2+ /Mn2+ -transport ATPase isoform 1 (SPCA1)...
March 14, 2024: Glia
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