Article
Cell Biology
Luisa Strackeljan, Ewa Baczynska, Carla Cangalaya, David Baidoe-Ansah, Jakub Wlodarczyk, Rahul Kaushik, Alexander Dityatev
Summary: Microglia play a role in regulating the remodeling of perineuronal nets (PNNs) and perisynaptic extracellular matrix (ECM), as well as the fine structure of PNNs and excitatory terminals in the hippocampus.
Review
Biochemistry & Molecular Biology
Alyssa Soles, Adem Selimovic, Kaelin Sbrocco, Ferris Ghannoum, Katherine Hamel, Emmanuel Labrada Moncada, Stephen Gilliat, Marija Cvetanovic
Summary: The extracellular matrix (ECM) surrounds cells in the brain and plays important roles in development, the healthy adult brain, and brain diseases. This review discusses the physiological roles of the ECM, its contribution to the pathogenesis of brain disease, and the involvement of gene expression changes, transcriptional factors, and microglia in ECM regulation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Jing Zheng, Wenqiu Zhang, Longqian Liu, Maurice Keng Hung Yap
Summary: The decline of visual plasticity restricts the recovery of visual functions in adult amblyopia. Repetitive transcranial magnetic stimulation (rTMS) has been shown to be effective in treating adult amblyopia by enhancing functional recovery and visual plasticity. This study found that low-frequency rTMS reinstated the amplitude of visual evoked potentials and increased the expression of synaptic plasticity genes and the number of dendritic spines in amblyopic rats. Furthermore, histological investigations revealed reduced levels of inhibition and perineuronal nets in the visual cortex.
FRONTIERS IN NEUROSCIENCE
(2023)
Review
Neurosciences
Bhanu P. P. Tewari, Lata Chaunsali, Courtney E. E. Prim, Harald Sontheimer
Summary: The extracellular matrix (ECM) and perineuronal nets (PNNs) serve as structural scaffolds in the central nervous system (CNS) with diverse functions, including neurogenesis, cell migration and differentiation, axonal growth, and synaptic stability. Glial cells play a key role in regulating the malleability of ECM and PNNs, impacting their functions in both health and diseases.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Midori L. L. Wasielewski, Katherine Nguyen, Srilakshmi Yalavarthi, Pallavi Ekbote, Priyan D. D. Weerappuli, Jason S. S. Knight, Shuichi Takayama
Summary: This study analyzed the degradation of millimeter-scale, circular DNA-histone mesostructures (DHMs) by nucleases and serum. It was found that DHMs had a less accessible chromatin structure compared to neutrophil extracellular traps (NETs), as they were degraded well by DNase I but not by micrococcal nuclease (MNase). Moreover, DHMs were degraded by normal human serum at a slower rate than NETs and showed qualitative differences in the degradation process compared to DNase I. Importantly, DHMs mimicked NETs in terms of their susceptibility to degradation by serum from a lupus patient with high disease activity. These findings have implications for the development and use of DHMs in extracellular chromatin-related pathophysiological and diagnostic studies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Giada Mascio, Serena Notartomaso, Katiuscia Martinello, Francesca Liberatore, Domenico Bucci, Tiziana Imbriglio, Milena Cannella, Nico Antenucci, Pamela Scarselli, Roberta Lattanzi, Valeria Bruno, Ferdinando Nicoletti, Sergio Fucile, Giuseppe Battaglia
Summary: Chronic inflammatory pain leads to the accumulation of perineuronal nets in cortical regions, and their degradation can reduce pain and modulate neuronal activity in the pain matrix.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Neurosciences
J. Sanchez-Ventura, L. Gimenez-Llort, C. Penas, E. Udina
Summary: PNN is a promising candidate for harnessing neural plasticity, especially in rehabilitation. SCI reduces PNN density in the spinal cord, while activity-based therapies can reverse this decrease and improve functional recovery.
EXPERIMENTAL NEUROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Barbara Sitas, Mihaela Bobic-Rasonja, Goran Mrak, Sara Trnski, Magdalena Krbot Skoric, Darko Oreskovic, Vinka Knezovic, Zeljka Petelin Gadze, Zdravko Petanjek, Goran Simic, Danijela Kolenc, Natasa Jovanov Milosevic
Summary: This study evaluated the ECM profile of HS1 in drug-resistant MTLE patients and found changes in PNNs, ECM proteins, and glycosylation patterns associated with the condition. These findings suggest that ECM molecules and their modulators could be potential targets for developing new therapeutic approaches to drug-resistant epilepsy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Jianqin Xue, Yu Zhang, Junhua Zhang, Zhujun Zhu, Qi Lv, Jianhua Su
Summary: This study revealed the important role of astrocyte-derived CCL7 in promoting microglia-mediated inflammation after TBI, suggesting CCL7 could serve as a potential therapeutic strategy for attenuating TBI by inhibiting microglial activation.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Huiqian Huang, Amelie M. Joffrin, Yuan Zhao, Gregory M. Miller, Grace C. Zhang, Yuki Oka, Linda C. Hsieh-Wilson
Summary: This study demonstrates that 4-O-sulfated chondroitin sulfate polysaccharides play a critical role in the regulation of perineuronal nets (PNNs) and synapse development in the mouse hippocampus, impacting anxiety and cognitive functions such as social memory. Alterations in CS 4-O-sulfation lead to imbalanced synaptic ratios, elevated anxiety levels, and social memory dysfunction. Modulating CS 4-O-sulfation levels reversibly affects PNN densities and the balance of excitatory and inhibitory synapses. Targeting CS 4-O-sulfation may offer therapeutic potential for addressing neuropsychiatric and neurodegenerative diseases associated with social cognitive dysfunction.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Clinical Neurology
Ana Paula Pesarico, Hector Carceller, Ramon Guirado, Simona Coviello, Juan Nacher
Summary: This study found that a single intense stressful event can produce long-term alterations in the inhibitory circuits of the BLA, especially on PV+ neurons and their plasticity, with a differential impact depending on the sex and the fear-related circuits involved.
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
(2022)
Article
Chemistry, Multidisciplinary
Yingwu Shi, Xun Wu, Jinpeng Zhou, Wenxing Cui, Jin Wang, Qing Hu, Shenghao Zhang, Liying Han, Meixuan Zhou, Jianing Luo, Qiang Wang, Haixiao Liu, Dayun Feng, Shunnan Ge, Yan Qu
Summary: This study investigates the transcriptional changes in different cell types of the amygdala after traumatic brain injury (TBI) using single-nucleus RNA sequencing (snRNA-seq). The results show that there are widespread transcriptional changes in each cell type after TBI. It is demonstrated that Decorin (Dcn) expression in the amygdala increases after TBI and plays a role in fear conditioning by regulating perineuronal nets (PNNs).
Article
Immunology
Pin-yi Liu, Hui-qin Li, Meng-qi Dong, Xin-ya Gu, Si-yi Xu, Sheng-nan Xia, Xin-yu Bao, Yun Xu, Xiang Cao
Summary: Properdin activates Mincle receptors on microglia to drive inflammatory responses, exacerbating brain injury in ischemic stroke patients. The interaction between properdin and Mincle on microglia may be a potential therapeutic target for improving ischemic stroke prognosis.
JOURNAL OF NEUROINFLAMMATION
(2023)
Article
Immunology
Xin Zhou, Rui Zhao, Mengfei Lv, Xiangyu Xu, Wenhao Liu, Xiaohua Li, Yunyi Gao, Zhiyuan Zhao, Zhaolong Zhang, Yuxuan Li, Rui Xu, Qi Wan, Yu Cui
Summary: In this study, ACSL4 was found to play an important role in polyunsaturated fatty acid metabolism. It was revealed that ACSL4 increased after LPS stimulation and knocking down ACSL4 reduced proinflammatory cytokine production in microglia. Mechanistically, ACSL4 regulated NF-kappa B signal transduction by reducing VGLL4 expression and also had an effect on lipid composition after LPS stimulation. Moreover, knocking down ACSL4 alleviated neuroinflammation in both a systemic LPS model and an acute MPTP model.
BRAIN BEHAVIOR AND IMMUNITY
(2023)
Article
Multidisciplinary Sciences
Rui Chen, Peng Li, Yan Fu, Zongyao Wu, Lijun Xu, Junhua Wang, Sha Chen, Mingzhen Yang, Bingjie Peng, Yao Yang, Hongwei Zhang, Qi Han, Shuhui Li
Summary: Evidence shows that chaperone-mediated autophagy (CMA) plays a role in cancer cell pathogenesis and progression, but its potential role in breast cancer angiogenesis is not known. By manipulating CMA activity in breast cancer cells, researchers found that CMA promotes breast cancer angiogenesis through the regulation of hexokinase 2-dependent aerobic glycolysis. These findings suggest that CMA may serve as a potential target for breast cancer therapies.
Article
Anesthesiology
Magali Millecamps, Susana G. Sotocinal, Jean-Sebastien Austin, Laura S. Stone, Jeffrey S. Mogil
Summary: Human epidemiological studies indicate that chronic pain may increase the risk of mortality. This study on mice reveals sex-specific patterns in pain behavior and suggests that the biology of chronic pain in humans is not adequately represented in current preclinical pain research.
Article
Clinical Neurology
Kleanthi Chalkiadaki, Mehdi Hooshmandi, Gilliard Lach, Elpida Statoulla, Konstanze Simbriger, Ines S. Amorim, Stella Kouloulia, Maria Zafeiri, Panagiotis Pothos, Eric Bonneil, Ilse Gantois, Jelena Popic, Sung-Hoon Kim, Calvin Wong, Ruifeng Cao, Noboru H. Komiyama, Yaser Atlasi, Seyed Mehdi Jafarnejad, Arkady Khoutorsky, Christos G. Gkogkas
Summary: MAPK interacting protein kinases 1 and 2 (Mnk1/2) regulate various functions by phosphorylating their substrate eIF4E on Ser209. Deletion of Mnk1/2 impairs synaptic plasticity and memory in mice, but ablation of phospho-eIF4E (Ser209) has no effect on these processes, indicating that Mnk1/2 have additional downstream effectors in the brain. Synaptic Ras GTPase activating protein 1 (Syngap1), encoded by an autism gene, is identified as a downstream target of Mnk1. Knockdown of Syngap1 reverses memory deficits in Mnk double knockout mice and pharmacological inhibition of Mnks rescues autism-related phenotypes in Syngap1(+/-) mice.
Article
Neurosciences
Xuhui Ge, Wu Ye, Yufeng Zhu, Min Cui, Jiawen Zhou, Chenyu Xiao, Dongdong Jiang, Pengyu Tang, Jiaxing Wang, Zhuanghui Wang, Chengyue Ji, Xuhui Zhou, Xiaojian Cao, Wei Liu, Weihua Cai
Summary: RNA N6-methyladenosine (m6A) modification plays an important role in spinal cord injury (SCI). Increased m6A level and upregulated METTL3 in reactive astrocytes are observed after SCI. The USP1/UAF1 complex stabilizes METTL3 by removing its K48-linked ubiquitination. Conditional knockout of astrocytic METTL3 suppresses reactive astrogliosis after SCI, leading to detrimental effects on functional recovery. METTL3 selectively methylates the YAP1 transcript and maintains its stability in an IGF2BP2-dependent manner. Overexpression of YAP1 partly reverses the effects of METTL3 knockout on functional recovery after SCI. Additionally, METTL3's methyltransferase activity is essential for reactive astrogliosis and motor repair.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Anesthesiology
Wataru Nemoto, Dalia Kozak, Susana G. Sotocinal, Shannon Tansley, Kirsty Bannister, Jeffrey S. Mogil
Summary: Descending control of nociception (DCN) is a reversible biomarker of chronic pain and can be manipulated through neurochemical modulation. This research provides insight into potential pharmacological strategies for preventing persistent pain.
Article
Cell Biology
Noosha Yousefpour, Samantha Locke, Haley Deamond, Chengyang Wang, Lucas Marques, Manon St-Louis, Johanne Ouellette, Arkady Khoutorsky, Yves De Koninck, Alfredo Ribeiro-da-Silva
Summary: Neuropathic pain is a debilitating condition caused by nerve system damage, and the imbalance of spinal excitation and inhibition is believed to contribute to it. Little is known about the structural basis of this imbalance. Through a preclinical model of neuropathic pain, researchers have found that microglia selectively engulf spinal synapses of central neurons but not peripheral sensory neurons. They also discovered that the removal of inhibitory and excitatory synapses occurs in different temporal patterns, with microglia-mediated inhibitory synapse removal happening before excitatory synapse removal. Additionally, they observed a gradual increase in complement depositions on dorsal horn synapses, which corresponds to the temporal pattern of microglial synapse pruning activity and specific synapse loss.
Article
Neurosciences
Mina N. Anadolu, Jingyu Sun, Senthilkumar Kailasam, Kleanthi Chalkiadaki, Konstanze Krimbacher, Jewel T. -Y. Li, Teodora Markova, Seyed M. Jafarnejad, Francois Lefebvre, Joaquin Ortega, Christos G. Gkogkas, Wayne S. Sossin
Summary: The granule fraction contains proteins implicated in stalled polysome function, and the ribosomes in this fraction are mainly stalled in the hybrid state. Ribosome profiling reveals longer footprints on mRNAs associated with FMRPs and an increase in ribosome occupancy on mRNAs encoding RNA binding proteins. The data supports a model in which specific sequences in mRNAs stall ribosomes during translation elongation in neurons.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Neurosciences
Xinying Zhang, Magali Millecamps, Artur Kania
Summary: The development of chronic neuropathic pain states is influenced by abnormal function of peripheral sensory neurons, leading to central sensitization and maladaptive plasticity in the spinal dorsal horn. This eventually affects supraspinal areas and causes cognitive and affective co-morbidities such as anxiety and depression. The study focuses on the role of spinal projection neurons, specifically the Phox2a AS neurons, in the generation and maintenance of chronic neuropathic pain. The loss of Phox2a attenuated the development of cold hyperalgesia and anxio-depressive-like behaviors in mice, highlighting the critical role of Phox2a AS neurons in chronic pain.
Article
Computer Science, Interdisciplinary Applications
Shan Ren, Lichun Shi, Yang Liu, Weihua Cai, Yingfeng Zhang
Summary: This study proposes a personalized maintenance approach (POMA-CP) to improve the accuracy and applicability of maintenance schemes for industrial products by establishing a refined maintenance model. The approach includes a multi-level case library, dynamic equipment portrait model, and case-pushing mechanism. Through this approach, active pushing of the best similar cases and automatic generation of service schemes can be achieved, resulting in higher accuracy and applicability for maintenance schemes.
ROBOTICS AND COMPUTER-INTEGRATED MANUFACTURING
(2023)
Article
Biochemistry & Molecular Biology
Xuhui Ge, Zheng Zhou, Siting Yang, Wu Ye, Zhuanghui Wang, Jiaxing Wang, Chenyu Xiao, Min Cui, Jiawen Zhou, Yufeng Zhu, Rixiao Wang, Yu Gao, Haofan Wang, Pengyu Tang, Xuhui Zhou, Ce Wang, Weihua Cai
Summary: Spinal cord injury (SCI) often leads to irreversible sensory and motor disabilities without effective treatment options. This study aimed to investigate the role of vascular endothelial cells in the polarization of microglia/macrophages and the underlying mechanism. The findings demonstrated that microglia/macrophages were shifted towards the M2 phenotype, mitochondrial impairment was alleviated, and reactive oxygen species (ROS) production was reduced by the administration of conditioned medium from microvascular endothelial cells. Exosomes derived from these endothelial cells were shown to promote motor rehabilitation and M2 polarization of microglia/macrophages in vivo. The study suggested that exosomes could be a promising therapeutic strategy for SCI treatment.
CELL AND BIOSCIENCE
(2023)
Article
Neurosciences
Xinying Guo, Gaolong Zhang, Weihua Cai, Fa Huang, Jingwen Qin, Xingrong Song
Summary: This study reveals the role of Rmst, a lncRNA, in damaged DRG neurons under neuropathic pain (NP) condition. Rmst is specifically expressed in injured DRG neurons and is upregulated following peripheral nerve damage. Overexpression of Rmst causes neuropathic symptoms, while blocking Rmst expression alleviates pain hypersensitivities and downregulates Dnmt3a expression. The study also shows that peripheral nerve damage-induced Rmst increase interacts with HuR to stabilize Dnmt3a mRNA. Overall, this research provides insight into the mechanism of NP and identifies Rmst as a potential target for drug development.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2023)
Article
Cell Biology
Kleanthi Chalkiadaki, Elpida Statoulla, Maria Zafeiri, Nabila Haji, Jean-Claude Lacaille, Craig M. Powell, Seyed Mehdi Jafarnejad, Arkady Khoutorsky, Christos G. Gkogkas
Summary: Inhibition of Nlgn1 expression in TSC mouse models can rescue cognitive and social behavior deficits without affecting mTORC1 hyperactivation.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Engineering, Biomedical
Yuluo Rong, Zhuanghui Wang, Pengyu Tang, Jiaxing Wang, Chengyue Ji, Jie Chang, Yufeng Zhu, Wu Ye, Jianling Bai, Wei Liu, Guoyong Yin, Lipeng Yu, Xuhui Zhou, Weihua Cai
Summary: In this study, a drug delivery system using engineered extracellular vesicles (EVs) carrying CAQK-modified peptide and loaded siRNA (C-EVs-siRNA) was designed for targeted therapy of spinal cord injury (SCI). The modified EVs effectively delivered siRNA to the SCI region and showed favorable therapeutic effects. The combination of targeted modified EVs and siRNA enhanced the anti-inflammatory and neuroreparative functions of EVs, promoting functional recovery in mice after SCI. This study highlights the potential of engineered EVs as a feasible and efficacious treatment for SCI and possibly other diseases.
BIOACTIVE MATERIALS
(2023)
Article
Multidisciplinary Sciences
Sudarshan Patil, Kleanthi Chalkiadaki, Tadiwos F. Mergiya, Konstanze Krimbacher, Ines S. Amorim, Shreeram Akerkar, Christos G. Gkogkas, Clive R. Bramham
Summary: The phosphorylation of eIF4E plays a critical role in the translational control of long-term synaptic plasticity and the selective translation of the Wnt signaling pathway. Phospho-ablated Eif4e(S209A) Knockin mice exhibit impaired maintenance of dentate gyrus LTP, while the basal perforant path-evoked transmission and LTP induction are unaffected. These findings suggest that activity-induced eIF4E phosphorylation is essential for LTP maintenance and the regulation of the mRNA cap-binding complex.
Article
Medicine, Research & Experimental
Patricia Soriano Roque, Carolina Thorn Perez, Mehdi Hooshmandi, Calvin Wong, Mohammad Javad Eslamizade, Shilan Heshmati, Nicole Brown, Vijendra Sharma, Kevin C. Lister, Vanessa Magalie Goyon, Laura Neagu-Lund, Cathy Shen, Nicolas Daccache, Hiroaki Sato, Tamaki Sato, Jeffrey S. Mogil, Karim Nader, Christos G. Gkogkas, Mihaela D. Iordanova, Masha Prager-Khoutorsky, Heidi M. McBride, Jean-Claude Lacaille, Linda Wykes, Thomas Schricker, Arkady Khoutorsky
Summary: Repeated or prolonged general anesthesia during the early postnatal period leads to long-lasting impairments in memory formation by causing selective apoptosis and loss of parvalbumin-positive inhibitory interneurons in the hippocampus of mice. This loss disrupts the regulation of neuronal circuits and memory consolidation. Preventing the loss of parvalbumin neurons rescues anesthesia-induced deficits in pyramidal cell inhibition and long-term memory, while partial depletion of these neurons in neonates is sufficient to impair long-term memory.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
