Review
Biochemistry & Molecular Biology
Shotaro Michinaga, Yutaka Koyama
Summary: Traumatic brain injury (TBI) is immediate damage to the brain caused by a blow to the head, resulting in death or serious disabilities. Astrocytes play a key role in the pathogenesis of TBI, with both beneficial and detrimental effects. They are attractive targets for novel therapeutic drugs for TBI, although such drugs have not yet been developed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
Yuancheng Weng, Ningting Chen, Rui Zhang, Jian He, Xukai Ding, Guo Cheng, Qianqian Bi, Ying-mei Lu, Xiao Z. Shen, Shu Wan, Peng Shi
Summary: This study reveals that microglia is the primary cellular source of PDGFB in adults, and microglial PDGFB is crucial for maintaining BBB integrity in adult mice.
BRAIN BEHAVIOR AND IMMUNITY
(2024)
Article
Biochemistry & Molecular Biology
Shi Yi Chia, Boon-Keat Khor, Yi Juin Tay, Kok Fui Liew, Chong-Yew Lee
Summary: Sulfuretin, a naturally occurring aurone, has been found to inhibit macrophage and microglia activation. In this study, a series of aurones were synthesized to improve their activity in targeting brain microglia and overcoming the blood-brain barrier. Evaluation of these aurones showed that some compounds were able to significantly reduce nitric oxide secretion in stimulated microglia. The most potent inhibitors had bulky, planar moieties and a pendant piperidine, and they inhibited microglial polarization towards the M1 state. Compound 2a showed high blood-brain barrier permeability and could potentially be used as a lead compound in the development of aurones as microglia inhibitors.
BIOORGANIC CHEMISTRY
(2023)
Article
Environmental Sciences
Shan Shan, Yifan Zhang, Huiwen Zhao, Tao Zeng, Xiulan Zhao
Summary: The study found that 50 nm polystyrene nanoplastics (PS-NPs) could pass through the blood-brain barrier (BBB) and accumulate in the brains of mice, leading to activation of microglia and damage to neurons. In vitro studies also showed that PS-NPs could be internalized by cells and caused the production of reactive oxygen species (ROS), activation of nuclear factor kappa-B (NF-kappa B), secretion of tumor necrosis factors alpha (TNF-alpha), and cell death.
Article
Biochemistry & Molecular Biology
Zhengzheng Ruan, Dongdong Zhang, Ruixue Huang, Wei Sun, Liyan Hou, Jie Zhao, Qingshan Wang
Summary: Chronic neuroinflammation damages dopaminergic neurons in a rotenone-induced mouse PD model through blood-brain barrier dysfunction mediated by microglial MMP-2/-9 activation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Atsuko Katsumoto, Olga N. Kokiko-Cochran, Shane M. Bemiller, Guixiang Xu, Richard M. Ransohoff, Bruce T. Lamb
Summary: This study found that traumatic brain injury promotes Alzheimer's disease-like pathological features and that deficiency of TREM2 accelerates inflammation and neurodegeneration, leading to brain damage and impaired neurological function.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biology
Xin-Yao Sun, Xiang-Chun Ju, Yang Li, Peng-Ming Zeng, Jian Wu, Ying-Ying Zhou, Li-Bing Shen, Jian Dong, Yue-Jun Chen, Zhen-Ge Luo
Summary: This study successfully fused blood vessels and brain organoids to obtain vascularized brain organoids. The fused organoids not only had vascular network-like structures and increased number of neural progenitors, but also contained functional blood-brain barrier-like structures and microglial cells with immune functions.
Editorial Material
Biology
Bilal Cakir, In-Hyun Park
Summary: When brain organoids are fused with blood vessel organoids, non-neural endothelial cells and microglia are incorporated into the brain organoids.
Article
Engineering, Biomedical
Qianru Yang, Alberto L. Vazquez, Xinyan Tracy Cui
Summary: Advancements in in vivo imaging technologies, such as two-photon microscopy, have improved our understanding of biomaterials in the brain, but chronic studies show limitations in high-resolution imaging due to inflammatory responses caused by craniotomy and foreign biomaterial insertion. Microprisms offer a unique vertical view breaking through this imaging depth limitation, but responses to microprism implants in vivo remain unclear. Analysis of microglial/macrophage activation and morphology after microprism implantation revealed changes in cell density and processes, indicating eventual inactive phenotypes. Long-term observations using microprisms showed sustained microglial/macrophage responses to injuries, suggesting feasibility for inflammatory response characterizations at deeper depths than traditional methods.
Article
Geriatrics & Gerontology
Christina Hoyer-Kimura, Meredith Hay, John P. Konhilas, Helena W. Morrison, Methawasin Methajit, Joshua Strom, Robin Polt, Victoria Salcedo, Joshua P. Fricks, Anjna Kalya, Paulo W. Pires
Summary: It is well known that decreased brain blood flow, increased reactive oxygen species production, and pro-inflammatory mechanisms accelerate neurodegenerative disease progressions. This study demonstrates that treatment with the novel drug PNA5 can reverse cognitive deficits, decrease ROS production, and inhibit inflammatory cytokine production, suggesting its potential as an effective therapy for treating and preventing VCID.
Review
Cell Biology
Ming Zhao, Xue-Fan Jiang, Hui-Qin Zhang, Jia-Hui Sun, Hui Pei, Li-Na Ma, Yu Cao, Hao Li
Summary: Alzheimer's disease is an irreversible neurodegenerative disorder with no satisfying curative therapies currently available. Dysfunction of the blood-brain barrier contributes to the onset and progression of AD, yet the pathogenesis caused by BBB injury remains unclear. Glial cells play a crucial role in maintaining the integrity of BBB and neuronal function.
AGEING RESEARCH REVIEWS
(2021)
Article
Clinical Neurology
Andrew G. Murchison
Summary: This article posits that amyloid deposition and increased permeability of the blood-brain barrier are early independent events in Alzheimer's disease pathophysiology, contributing to a distinct microglial activation phenotype. Downstream effects such as synapse phagocytosis and persistent glutamate signally through NMDA receptors lead to neurodegeneration and tau pathology. This hypothesis aims to shed light on unexplained temporal and spatial features of AD by drawing from multiple lines of evidence.
ALZHEIMERS & DEMENTIA
(2022)
Article
Clinical Neurology
Diogo Vila Verde, Marco de Curtis, Laura Librizzi
Summary: This study demonstrates that epileptiform seizure-like events can induce the activation of astrocytes and microglia, and that serum albumin extravasation exacerbates this activation, potentially leading to reinforcement of seizure activity.
FRONTIERS IN NEUROLOGY
(2021)
Article
Neurosciences
A. D. Roseborough, Y. Zhu, L. Zhao, S. R. Laviolette, S. H. Pasternak, S. N. Whitehead
Summary: The brain's response to acute injury involves increased permeability of the blood-brain barrier (BBB) and increased inflammation in microglia, which can lead to poor cognitive outcomes and neurological disease. Fibrinogen, a serum protein, enters the brain through the damaged BBB and interacts with local cells in a harmful way. Microglia, in response to injury, demonstrate increased activity of the NLRP3 inflammasome and release more pro-inflammatory cytokines. This study investigates the interaction between fibrinogen, microglial NLRP3 signaling, and extracellular vesicles (EVs), which can propagate inflammatory signaling and be detected in the circulation following BBB disruption.
NEUROBIOLOGY OF DISEASE
(2023)
Review
Neurosciences
Agatha Oliveira-Giacomelli, Lyvia Lintzmaier Petiz, Roberta Andrejew, Natalia Turrini, Jean Bezerra Silva, Ulrich Sack, Henning Ulrich
Summary: P2X7 receptors are activated by ATP, leading to inflammatory pathways and cytokine release, increasing BBB permeability. Besides its involvement in neurodegenerative diseases and neuroinflammation, P2X7 receptor activation may disrupt BBB and attract peripheral immune cells to the CNS, causing brain parenchyma infiltration.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Neurosciences
Patricia Rivera, Santiago Guerra-Cantera, Antonio Vargas, Francisca Diaz, Rocio Garcia-Ubeda, Ruben Tovar, Maria Teresa Ramirez-Lopez, Jesus Argente, Fernando Rodriguez de Fonseca, Juan Suarez, Julie A. Chowen
Summary: This study aimed to investigate the long-lasting effects of maternal malnutrition during gestation/lactation on inflammation, lipid metabolism, and endocannabinoid signaling in the adult offspring hypothalamus, as well as the role of hypothalamic astrocytes in these changes. The results showed that maternal malnutrition caused sex-specific alterations in hypothalamic endocannabinoid signaling and lipid metabolism. Additionally, hypothalamic astrocytes were found to play a possible role in this process.
NUTRITIONAL NEUROSCIENCE
(2022)
Review
Cell Biology
Tiemin Liu, Yong Xu, Chun-Xia Yi, Qingchun Tong, Dongsheng Cai
Summary: This review highlights the link between brain dysfunction and genetic mutations, sex, brain inflammation, microbiota, and stress as causes of whole-body pathophysiology. Studies suggest that dysfunction in the brain's perception and processing of internal and external cues can have profound effects on metabolism and other physiological functions.
Article
Cell Biology
Julie A. Chowen, Luis M. Garcia-Segura
Summary: Diseases and changes in the nervous system related to aging often exhibit sex-specific characteristics, with glial cells playing a major role in the endogenous response of neural tissue. The sex-specific response of glial cells is influenced by sex chromosome genes, gonadal hormones, and neuroactive steroid hormone metabolites. This response may be crucial in understanding and potentially treating sex differences in pathological alterations of the nervous system.
MECHANISMS OF AGEING AND DEVELOPMENT
(2021)
Article
Biochemistry & Molecular Biology
Xiao-Lan Wang, Sander Kooijman, Yuanqing Gao, Laura Tzeplaeff, Brigitte Cosquer, Irina Milanova, Samantha E. C. Wolff, Nikita Korpel, Marie-France Champy, Benoit Petit-Demouliere, Isabelle Goncalves Da Cruz, Tania Sorg-Guss, Patrick C. N. Rensen, Jean-Christophe Cassel, Andries Kalsbeek, Anne-Laurence Boutillier, Chun-Xia Yi
Summary: The study found that microglial Bmal1 plays a crucial role in metabolic stress and memory formation, as knocking it down led to enhanced phagocytosis activity and positive effects on neuronal activity in the brain, helping to combat obesity and improve memory test performance.
MOLECULAR PSYCHIATRY
(2021)
Article
Nanoscience & Nanotechnology
Shanshan Guo, Fernando Cazarez-Marquez, Han Jiao, Ewout Foppen, Nikita L. Korpel, Anita E. Grootemaat, Nalan Liv, Yuanqing Gao, Nicole van der Wel, Bing Zhou, Guangjun Nie, Chun-Xia Yi
Summary: This study introduces a method using lipid and polymer hybridized nanoparticles for local delivery of small interfering RNA (siRNA) to silence specific microglial genes in the hypothalamus. The researchers demonstrated the effectiveness of this method both in vitro and in vivo, showing significant reductions in gene expression and microglial activation.
ACS APPLIED MATERIALS & INTERFACES
(2022)
Article
Biochemistry & Molecular Biology
Paul de Goede, Rob C. Wust, Bauke Schomakers, Simone Denis, Frederic M. Vaz, Mia L. Pras-Raves, Michel Weeghel, Chun-Xia Yi, Andries Kalsbeek, Riekelt H. Houtkooper
Summary: Shift-work disrupts circadian timing of glucose homeostasis, impairs muscle mitochondrial metabolism, and causes metabolic inflexibility, increasing the risk of developing T2DM.
Article
Neurosciences
Natalia Yanguas-Casas, Cristina Torres, Andrea Crespo-Castrillo, Sonia Diaz-Pacheco, Kiera Healy, Catherine Stanton, Julie A. Chowen, Luis M. Garcia-Segura, Maria Angeles Arevalo, John F. Cryan, Maria L. de Ceballos
Summary: Long-term high-fat diet can lead to obesity and inflammation, affecting gut microbiota. The effects of diet vary between sexes and genotypes of mice, with female TgAPP mice showing some resistance to diet-induced effects.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Neurosciences
Jesus Fernandez-Felipe, Maria Valencia-Avezuela, Beatriz Merino, Beatriz Somoza, Victoria Cano, Ana B. Sanz-Martos, Laura M. Frago, Maria S. Fernandez-Alfonso, Mariano Ruiz-Gayo, Julie A. Chowen
Summary: This study found that diets rich in fatty acids can increase body weight and adiposity, even without increased energy intake. Different intake of saturated and unsaturated fatty acids can differentially modify metabolic parameters. Further research is needed to understand how specific nutrients affect metabolism and obesity-associated complications.
NUTRITIONAL NEUROSCIENCE
(2023)
Article
Endocrinology & Metabolism
J. Fernandez-Felipe, B. Merino, A. B. Sanz-Martos, A. Plaza, A. Contreras, V Naranjo, L. Morales, J. A. Chowen, V Cano, M. Ruiz-Gayo, N. Del Olmo
Summary: Chronic consumption of both SOLF and UOLF impairs spatial short-term memory, modulates hippocampal synaptic plasticity mechanisms and gene expression of NMDA receptor subunits. PPAR gamma gene expression is specifically down-regulated in adolescent SOLF individuals and up-regulated in adult UOLF mice.
PSYCHONEUROENDOCRINOLOGY
(2021)
Article
Endocrinology & Metabolism
Santiago Guerra-Cantera, Laura M. Frago, Roberto Collado-Perez, Sandra Canelles, Purificacion Ros, Alejandra Freire-Regatillo, Maria Jimenez-Hernaiz, Vicente Barrios, Jesus Argente, Julie A. Chowen
Summary: Dietary intervention can impact metabolic hormones and glucose tolerance in male and female mice, with some parameters returning to normal levels after switching back to a standard diet, but with differences in the rate of recovery. Sex differences were also observed in the response to high fat diet and the switch to a normal diet, particularly in circulating levels of IGF2 and IGFBP2.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Eirini Vagena, Jasmina Crneta, Pauline Engstrom, Li He, Ernie Yulyaningsih, Nikita L. Korpel, Rachel T. Cheang, Tomas P. Bachor, Alyssa Huang, Guillermina Michel, Kush Attal, David Berrios, Martin Valdearcos, Suneil K. Koliwad, David P. Olson, Chun-Xia Yi, Allison W. Xu
Summary: Variants in the ASB4 gene are associated with human obesity. ASB4 acts in the brain to improve glucose homeostasis and induce satiety.
Article
Endocrinology & Metabolism
Kirk M. Habegger
Summary: While the consumption of external energy is vital to life, it temporarily disrupts homeostasis in animals. Regulation of glycemia, for example, is affected by the release of stored energy during fasting and the influx of diverse nutrients during feeding. The counterregulatory hormones epinephrine, growth hormone, cortisol, and glucagon play a key role in this regulation. Understanding the role of glucagon in the transition from fasting to feeding states is important for glycemic control.
Article
Biochemistry & Molecular Biology
Vicente Barrios, Santiago Guerra-Cantera, Alvaro Martin-Rivada, Sandra Canelles, Ana Campillo-Calatayud, Eduardo Arilla-Ferreiro, Laura M. Frago, Julie A. Chowen, Jesus Argente
Summary: Leptin is involved in regulating insulin signaling and lipid metabolism in peripheral tissues. This study found that leptin activates insulin signaling and reduces muscle inflammation parameters, while decreasing the levels of non-esterified fatty acids.
Article
Biochemistry & Molecular Biology
Olga M. Palomino, Veronica Giordani, Julie Chowen, Soledad Fernandez Alfonso, Luis Goya
Summary: Oxidative stress can lead to endothelial dysfunction and cardiovascular disease. Free fatty acids, particularly olive oil fatty acids, have beneficial effects on cardiovascular risk factors. Physiological concentrations of palmitic and oleic acids may protect vascular endothelium against oxidative stress.
Article
Biochemistry & Molecular Biology
Irina Milanova, Nikita L. Korpel, Felipe Correa-da-Silva, Eline Berends, Samar Osman, Susanne E. la Fleur, Eric Fliers, Andries Kalsbeek, Chun-Xia Yi
Summary: The study found that microglial insulin signaling plays a role in the control of systemic energy balance and this function is sex-dependent. Lack of microglial InsR can lead to increased plasma insulin levels and insulin resistance in female obese mice.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)