keyword
https://read.qxmd.com/read/37729550/lipid-nanoparticles-deliver-mrna-to-the-brain-after-an-intracerebral-injection
#21
JOURNAL ARTICLE
Jan Tuma, Yu-Ju Chen, Michael G Collins, Abhik Paul, Jie Li, Hesong Han, Rohit Sharma, Niren Murthy, Hye Young Lee
Neurological disorders are often debilitating conditions with no cure. The majority of current therapies are palliative rather than disease-modifying; therefore, new strategies for treating neurological disorders are greatly needed. mRNA-based therapeutics have great potential for treating such neurological disorders; however, challenges with delivery have limited their clinical potential. Lipid nanoparticles (LNPs) are a promising delivery vector for the brain, given their safer toxicity profile and higher efficacy...
September 20, 2023: Biochemistry
https://read.qxmd.com/read/37720086/lethal-adulthood-myelin-breakdown-by-oligodendrocyte-specific-ddx54-knockout
#22
JOURNAL ARTICLE
Hiroaki Oizumi, Yuki Miyamoto, Chika Seiwa, Masahiro Yamamoto, Nozomu Yoshioka, Seiichi Iizuka, Tomohiro Torii, Katsuya Ohbuchi, Kazushige Mizoguchi, Junji Yamauchi, Hiroaki Asou
Multiple sclerosis (MS) is a leading disease that causes disability in young adults. We have previously shown that a DEAD-box RNA helicase Ddx54 binds to mRNA and protein isoforms of myelin basic protein (MBP) and that Ddx54 siRNA blocking abrogates oligodendrocyte migration and myelination. Herein, we show that MBP-driven Ddx54 knockout mice ( Ddx54 fl/fl;MBP-Cre ), after the completion of normal postnatal myelination, gradually develop abnormalities in behavioral profiles and learning ability, inner myelin sheath breakdown, loss of myelinated axons, apoptosis of oligodendrocytes, astrocyte and microglia activation, and they die within 7 months but show minimal peripheral immune cell infiltration...
October 20, 2023: IScience
https://read.qxmd.com/read/37639128/translatome-profiling-of-tissue-resident-macrophages-using-the-ribotag-approach
#23
JOURNAL ARTICLE
Jung-Seok Kim, Zhana Haimon, Sigalit Boura-Halfon, Steffen Jung
Global gene expression profiling has provided valuable insights into the specific contributions of different cell types to various physiological processes. Notably though, both bulk and single-cell transcriptomics require the prior retrieval of the cells from their tissue context to be analyzed. Isolation protocols for tissue macrophages are, however, notoriously inefficient and, moreover, prone to introduce considerable bias and artifacts. Here, we will discuss a valuable alternative, originally introduced by Amieux and colleagues...
2024: Methods in Molecular Biology
https://read.qxmd.com/read/37635351/a-comparative-analysis-of-microglial-inducible-cre-lines
#24
JOURNAL ARTICLE
Travis E Faust, Philip A Feinberg, Ciara O'Connor, Riki Kawaguchi, Andrew Chan, Hayley Strasburger, Maximilian Frosch, Margaret A Boyle, Takahiro Masuda, Lukas Amann, Klaus-Peter Knobeloch, Marco Prinz, Anne Schaefer, Dorothy P Schafer
Cre/loxP technology has revolutionized genetic studies and allowed for spatial and temporal control of gene expression in specific cell types. Microglial biology has particularly benefited because microglia historically have been difficult to transduce with virus or electroporation methods for gene delivery. Here, we investigate five of the most widely available microglial inducible Cre lines. We demonstrate varying degrees of recombination efficiency, cell-type specificity, and spontaneous recombination, depending on the Cre line and inter-loxP distance...
August 26, 2023: Cell Reports
https://read.qxmd.com/read/37503044/genetic-dissection-of-bdnf-and-trkb-expression-in-glial-cells
#25
Changran Niu, Xinpei Yue, Juan Ji An, Haifei Xu, Baoji Xu
The brain-derived neurotrophic factor (BDNF) and its high-affinity receptor tropomyosin-related kinase receptor B (TrkB) are widely expressed in the central nervous system. It is well documented that neurons express BDNF and full-length TrkB (TrkB.FL), and a lower level of truncated TrkB (TrkB.T). With conflicting results, glial cells also have been reported to express BDNF and TrkB. In the current study, we employed a more sensitive and reliable genetic method to characterize the expression of BDNF and TrkB in glial cells in the mouse brain...
July 25, 2023: bioRxiv
https://read.qxmd.com/read/37455566/dynamics-of-reactive-astrocytes-fosters-tissue-regeneration-after-cuprizone-induced-demyelination
#26
JOURNAL ARTICLE
Lara-Jasmin Schröder, Felix Mulenge, Andreas Pavlou, Thomas Skripuletz, Martin Stangel, Viktoria Gudi, Ulrich Kalinke
Demyelination in the central nervous system (CNS) is a hallmark of many neurodegenerative diseases such as multiple sclerosis (MS) and others. Here, we studied astrocytes during de- and remyelination in the cuprizone mouse model. To this end, we exploited the ribosomal tagging (RiboTag) technology that is based on Cre-mediated cell type-selective HA-tagging of ribosomes. Analyses were performed in the corpus callosum of GFAP-Cre+/- Rpl22HA/wt mice 5 weeks after cuprizone feeding, at the peak of demyelination, and 0...
July 17, 2023: Glia
https://read.qxmd.com/read/37256881/early-chronic-suppression-of-microglial-p38%C3%AE-in-a-model-of-alzheimer-s-disease-does-not-significantly-alter-amyloid-associated-neuropathology
#27
JOURNAL ARTICLE
David J Braun, Hilaree N Frazier, Verda A Davis, Meggie J Coleman, Colin B Rogers, Linda J Van Eldik
The p38 alpha mitogen-activated protein kinase (p38α) is linked to both innate and adaptive immune responses and is under investigation as a target for drug development in the context of Alzheimer's disease (AD) and other conditions with neuroinflammatory dysfunction. While preclinical data has shown that p38α inhibition can protect against AD-associated neuropathology, the underlying mechanisms are not fully elucidated. Inhibitors of p38α may provide benefit via modulation of microglial-associated neuroinflammatory responses that contribute to AD pathology...
2023: PloS One
https://read.qxmd.com/read/37220747/in-the-mouse-cortex-oligodendrocytes-regain-a-plastic-capacity-transforming-into-astrocytes-after-acute-injury
#28
JOURNAL ARTICLE
Xianshu Bai, Na Zhao, Christina Koupourtidou, Li-Pao Fang, Veronika Schwarz, Laura C Caudal, Renping Zhao, Johannes Hirrlinger, Wolfgang Walz, Shan Bian, Wenhui Huang, Jovica Ninkovic, Frank Kirchhoff, Anja Scheller
Acute brain injuries evoke various response cascades directing the formation of the glial scar. Here, we report that acute lesions associated with hemorrhagic injuries trigger a re-programming of oligodendrocytes. Single-cell RNA sequencing highlighted a subpopulation of oligodendrocytes activating astroglial genes after acute brain injuries. By using PLP-DsRed1/GFAP-EGFP and PLP-EGFPmem /GFAP-mRFP1 transgenic mice, we visualized this population of oligodendrocytes that we termed AO cells based on their concomitant activity of astro- and oligodendroglial genes...
May 18, 2023: Developmental Cell
https://read.qxmd.com/read/37199240/microglia-specific-knock-out-of-nf-%C3%AE%C2%BAb-ikk2-increases-the-accumulation-of-misfolded-%C3%AE-synuclein-through-the-inhibition-of-p62-sequestosome-1-dependent-autophagy-in-the-rotenone-model-of-parkinson-s-disease
#29
JOURNAL ARTICLE
Savannah M Rocha, Kelly S Kirkley, Debotri Chatterjee, Tawfik A Aboellail, Richard J Smeyne, Ronald B Tjalkens
Parkinson's disease (PD) is the most common neurodegenerative movement disorder worldwide, with a greater prevalence in men than women. The etiology of PD is largely unknown, although environmental exposures and neuroinflammation are linked to protein misfolding and disease progression. Activated microglia are known to promote neuroinflammation in PD, but how environmental agents interact with specific innate immune signaling pathways in microglia to stimulate conversion to a neurotoxic phenotype is not well understood...
May 18, 2023: Glia
https://read.qxmd.com/read/37131606/finding-the-right-tool-a-comprehensive-evaluation-of-microglial-inducible-cre-mouse-models
#30
Alicia Bedolla, Gabriel Mckinsey, Kierra Ware, Nicolas Santander, Thomas Arnold, Yu Luo
The recent proliferation of new Cre and CreER recombinase lines provides researchers with a diverse toolkit to study microglial gene function. To determine how best to apply these lines in studies of microglial gene function, a thorough and detailed comparison of their properties is needed. Here, we examined four different microglial CreER lines ( Cx3cr1 CreER(Litt) , Cx3cr1 CreER(Jung) , P2ry12 CreER , Tmem119 CreER ), focusing on (1) recombination specificity; (2) leakiness - degree of non-tamoxifen recombination in microglia and other cells; (3) efficiency of tamoxifen-induced recombination; (4) extra-neural recombination -the degree of recombination in cells outside the CNS, particularly myelo/monocyte lineages (5) off-target effects in the context of neonatal brain development...
April 17, 2023: bioRxiv
https://read.qxmd.com/read/37084991/deletion-of-pten-in-microglia-ameliorates-chronic-neuroinflammation-following-repetitive-mtbi
#31
JOURNAL ARTICLE
Andrew Pearson, Camila Ortiz, Max Eisenbaum, Clara Arrate, Mackenzie Browning, Michael Mullan, Corbin Bachmeier, Fiona Crawford, Joseph O Ojo
Traumatic brain injury is a leading cause of morbidity and mortality in adults and children in developed nations. Following the primary injury, microglia, the resident innate immune cells of the CNS, initiate several inflammatory signaling cascades and pathophysiological responses that may persist chronically; chronic neuroinflammation following TBI has been closely linked to the development of neurodegeneration and neurological dysfunction. Phosphoinositide 3-kinases (PI3Ks) are a family of lipid kinases that have been shown to regulate several key mechanisms in the inflammatory response to TBI...
April 20, 2023: Molecular and Cellular Neurosciences
https://read.qxmd.com/read/37061460/the-alzheimer-s-disease-risk-factor-inpp5d-restricts-neuroprotective-microglial-responses-in-amyloid-beta-mediated-pathology
#32
JOURNAL ARTICLE
Joshua D Samuels, Katelyn A Moore, Hannah E Ennerfelt, Alexis M Johnson, Adeline E Walsh, Richard J Price, John R Lukens
INTRODUCTION: Mutations in INPP5D, which encodes for the SH2-domain-containing inositol phosphatase SHIP-1, have recently been linked to an increased risk of developing late-onset Alzheimer's disease. While INPP5D expression is almost exclusively restricted to microglia in the brain, little is known regarding how SHIP-1 affects neurobiology or neurodegenerative disease pathogenesis. METHODS: We generated and investigated 5xFAD Inpp5dfl/fl Cx3cr1Ert2Cre mice to ascertain the function of microglial SHIP-1 signaling in response to amyloid beta (Aβ)-mediated pathology...
April 15, 2023: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://read.qxmd.com/read/37023830/dissecting-the-neurovascular-unit-in-physiology-and-alzheimer-s-disease-functions-imaging-tools-and-genetic-mouse-models
#33
JOURNAL ARTICLE
Tiantian Li, Dianyi Li, Qingyuan Wei, Minghong Shi, Jiakun Xiang, Ruiwei Gao, Chao Chen, Zhi-Xiang Xu
The neurovascular unit (NVU) plays an essential role in regulating neurovascular coupling, which refers to the communication between neurons, glia, and vascular cells to control the supply of oxygen and nutrients in response to neural activity. Cellular elements of the NVU coordinate to establish an anatomical barrier to separate the central nervous system from the milieu of the periphery system, restricting the free movement of substances from the blood to the brain parenchyma and maintaining central nervous system homeostasis...
April 4, 2023: Neurobiology of Disease
https://read.qxmd.com/read/36991278/human-cytomegalovirus-ie2-disrupts-neural-progenitor-development-and-induces-microcephaly-in-transgenic-mouse
#34
JOURNAL ARTICLE
Delei Niu, Xianjuan Zhang, Shuyun Zhang, Tianyu Fan, Xiaoqiong Zhou, Hui Wang, Xueming Zhang, Fulong Nan, Shasha Jiang, Fengjun Liu, Yunyang Wang, Bin Wang
Human cytomegalovirus (HCMV) is a significant contributor to congenital birth defects. Limited by the lack of animal models, the pathogenesis of neurological damage in vivo caused by HCMV infection and the role of individual viral genes remain to be elucidated. Immediate early (IE2) protein may play a function in neurodevelopmental problems caused by HCMV infection. Here, this study intended to investigate IE2's long-term effects on development of the brain in IE2-expressing transgenic mice (Rosa26-LSL-IE2+/- , Camk2α-Cre) aimed to observe the phenotype of postnatal mice...
March 29, 2023: Molecular Neurobiology
https://read.qxmd.com/read/36890585/neurofibromatosis%C3%A2-type-1-dependent-alterations-in-mouse-microglia-function-are-not-cell-intrinsic
#35
JOURNAL ARTICLE
Francesca Logiacco, Laura Cathleen Grzegorzek, Elizabeth C Cordell, Oliver Popp, Philipp Mertins, David H Gutmann, Helmut Kettenmann, Marcus Semtner
We previously discovered a sex-by-genotype defect in microglia function using a heterozygous germline knockout mouse model of Neurofibromatosis type 1 (Nf1 ± mice), in which only microglia from male Nf1 ± mice exhibited defects in purinergic signaling. Herein, we leveraged an unbiased proteomic approach to demonstrate that male, but not female, heterozygous Nf1 ± microglia exhibit differences in protein expression, which largely reflect pathways involved in cytoskeletal organization...
March 9, 2023: Acta Neuropathologica Communications
https://read.qxmd.com/read/36872323/ifnar-signaling-of-neuroectodermal-cells-is-essential-for-the-survival-of-c57bl-6-mice-infected-with-theiler-s-murine-encephalomyelitis-virus
#36
JOURNAL ARTICLE
Melanie Bühler, Dandan Li, Lin Li, Sandra Runft, Inken Waltl, Andreas Pavlou, Ulrich Kalinke, Malgorzata Ciurkiewicz, Jochen Huehn, Stefan Floess, Andreas Beineke, Wolfgang Baumgärtner, Ingo Gerhauser
BACKGROUND: Theiler's murine encephalomyelitis virus (TMEV) is a single-stranded RNA virus that causes encephalitis followed by chronic demyelination in SJL mice and spontaneous seizures in C57BL/6 mice. Since earlier studies indicated a critical role of type I interferon (IFN-I) signaling in the control of viral replication in the central nervous system (CNS), mouse strain-specific differences in pathways induced by the IFN-I receptor (IFNAR) might determine the outcome of TMEV infection...
March 5, 2023: Journal of Neuroinflammation
https://read.qxmd.com/read/36828819/cd11c-microglia-promote-white-matter-repair-after-ischemic-stroke
#37
JOURNAL ARTICLE
Junqiu Jia, Lili Zheng, Lei Ye, Jian Chen, Shu Shu, Siyi Xu, Xinyu Bao, Shengnan Xia, Renyuan Liu, Yun Xu, Meijuan Zhang
Ischemic stroke leads to white matter damage and neurological deficits. However, the characteristics of white matter injury and repair after stroke are unclear. Additionally, the precise molecular communications between microglia and white matter repair during the stroke rehabilitation phase remain elusive. In this current study, MRI DTI scan and immunofluorescence staining were performed to trace white matter and microglia in the mouse transient middle cerebral artery occlusion (tMCAO) stroke model. We found that the most serious white matter damage was on Day 7 after the ischemic stroke, then it recovered gradually from Day 7 to Day 30...
February 24, 2023: Cell Death & Disease
https://read.qxmd.com/read/36791722/a-cre-deleter-specific-for-embryo-derived-brain-macrophages-reveals-distinct-features-of-microglia-and-border-macrophages
#38
JOURNAL ARTICLE
Simone Brioschi, Julia A Belk, Vincent Peng, Martina Molgora, Patrick Fernandes Rodrigues, Khai M Nguyen, Shoutang Wang, Siling Du, Wei-Le Wang, Gary E Grajales-Reyes, Jennifer M Ponce, Carla M Yuede, Qingyun Li, John M Baer, David G DeNardo, Susan Gilfillan, Marina Cella, Ansuman T Satpathy, Marco Colonna
Genetic tools to target microglia specifically and efficiently from the early stages of embryonic development are lacking. We generated a constitutive Cre line controlled by the microglia signature gene Crybb1 that produced nearly complete recombination in embryonic brain macrophages (microglia and border-associated macrophages [BAMs]) by the perinatal period, with limited recombination in peripheral myeloid cells. Using this tool in combination with Flt3-Cre lineage tracer, single-cell RNA-sequencing analysis, and confocal imaging, we resolved embryonic-derived versus monocyte-derived BAMs in the mouse cortex...
May 9, 2023: Immunity
https://read.qxmd.com/read/36786945/macrophage-microglia-sirt3-contributes-to-the-anti-inflammatory-effects-of-resveratrol-against-experimental-intracerebral-hemorrhage-in-mice
#39
JOURNAL ARTICLE
Jidong Sun, Chen Pu, ErWan Yang, Hongchen Zhang, Yuan Feng, Peng Luo, Yuefan Yang, Lei Zhang, Xia Li, Xiaofan Jiang, Shuhui Dai
Intracerebral hemorrhage (ICH) is a devastating stroke type with high mortality and disability. Inflammatory response induced by macrophages/microglia (M/Ms) activation is one of the leading causes of brain damage after ICH. The anti-inflammatory effects of resveratrol (RSV) have already been evaluated in several models of central nervous system disease. Therefore, we designed the current study to assess the role of RSV in ICH and explore its downstream mechanism related to Sirt3. The autologous artery blood injection was administrated to create an ICH mouse model...
February 14, 2023: Cellular and Molecular Neurobiology
https://read.qxmd.com/read/36769051/retinal-tissue-shows-glial-changes-in-a-dravet-syndrome-knock-in-mouse-model
#40
JOURNAL ARTICLE
Juan J Salazar, Andrea Satriano, José A Matamoros, José A Fernández-Albarral, Elena Salobrar-García, Inés López-Cuenca, Rosa de Hoz, Lidia Sánchez-Puebla, José M Ramírez, Cristina Alonso, Valentina Satta, Inés Hernández-Fisac, Onintza Sagredo, Ana I Ramírez
Dravet syndrome (DS) is an epileptic encephalopathy caused by mutations in the Scn1a gene encoding the α1 subunit of the Nav1.1 sodium channel, which is associated with recurrent and generalized seizures, even leading to death. In experimental models of DS, histological alterations have been found in the brain; however, the retina is a projection of the brain and there are no studies that analyze the possible histological changes that may occur in the disease. This study analyzes the retinal histological changes in glial cells (microglia and astrocytes), retinal ganglion cells (RGCs) and GABAergic amacrine cells in an experimental model of DS (Syn-Cre/Scn1aWT/A1783V ) compared to a control group at postnatal day (PND) 25...
February 1, 2023: International Journal of Molecular Sciences
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