Article
Engineering, Biomedical
Evgenii Kim, Jeungeun Kum, Hyungmin Kim
Summary: Compared to current non-invasive methods, focused ultrasound provides better spatial resolution and penetration depth. This study investigates the application of trans-spinal focused ultrasound (tsFUS) on a mouse model to modulate the descending pathways in a non-invasive manner. The results show the ability of tsFUS to modulate motor signals and manage tremors safely, providing a foundation for the trans-spinal application of focused ultrasound to motor-related disorders.
IEEE TRANSACTIONS ON NEURAL SYSTEMS AND REHABILITATION ENGINEERING
(2022)
Article
Neurosciences
Juan Mauricio Garre, Feliksas F. Bukauskas, Michael V. L. Bennett
Summary: This study investigated the single channel properties of three different surface channels involved in purinergic signaling in spinal astrocytes. The researchers found that Px1 HCs could be distinguished from Cx43 HCs and P2X7Rs based on their unitary conductance, voltage-dependence, and activity after pharmacological and gene silencing. Additionally, fibroblast growth factor 1 (FGF-1) was found to modulate the activity of these channels.
Article
Cell Biology
Norimitsu Morioka, Syun Kondo, Nanase Harada, Tomoyo Takimoto, Nozomi Tokunaga, Yoki Nakamura, Kazue Hisaoka-Nakashima, Yoshihiro Nakata
Summary: The study found that Cx43 knockdown can enhance the expression of BDNF mRNA in astrocytes, revealing a novel mechanism mediated by adrenergic receptors.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Article
Immunology
Sonia Kiran, Mousumi Mandal, Ahmed Rakib, Amandeep Bajwa, Udai P. Singh
Summary: This study investigates the role and mechanism of miR-10a-3p in adipose inflammation and adipogenesis using ex vivo and in vitro approaches. The findings suggest that miR-10a-3p mimic reduces the expression of inflammatory cells and cytokines, and induces the expression of FoxP3 in adipose tissue. In vitro experiments also show that miR-10a-3p mimic reduces the expression of inflammatory genes and lipid accumulation. This study provides a new opportunity for the development of miR-10a-3p as a novel therapeutic for adipose inflammation and its associated metabolic disorders.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Cell Biology
Han Zhang, Yu-Ming Hu, Ying-Jie Wang, Yue Zhou, Zhen-Jie Zhu, Min-Hao Chen, Yong-Jun Wang, Hua Xu, You-Hua Wang
Summary: Spinal cord injury leads to excessive inflammation, with accumulation of leukocytes at the lesion site. This study investigated the regulatory mechanism of resident cells in the spinal cord for the production of chemokines. It was found that macrophage migration inhibitory factor activation and its interaction with CD74 receptor play a role in producing chemokine C-C motif chemokine ligand 2 from astrocytes. Inhibiting macrophage migration inhibitory factor resulted in reduced recruitment of microglia/macrophages and improved hindlimb locomotor function after spinal cord injury. These findings provide insights into the role of astrocyte-activated chemokines and the potential for targeting chemokine C-C motif chemokine ligand 2 in treating neuroinflammation following spinal cord injury.
NEURAL REGENERATION RESEARCH
(2023)
Article
Neurosciences
Changnan Xie, Yihan Wang, Jinfeng Wang, Yizhou Xu, Haining Liu, Jiasong Guo, Lixin Zhu
Summary: This study found that Perlecan is specifically expressed in the basement membranes (BMs) of the spinal cord and undergoes degradation/remodeling after spinal cord injury (SCI). Overexpression of Perlecan significantly enhances locomotor recovery and neural regeneration, reduces blood-spinal cord barrier (BSCB) permeability, and decreases the neuroinflammatory response. Perlecan interacts with integrin beta 1 and inhibits downstream signaling pathway to improve BSCB integrity.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Immunology
Run Zhang, Biao Xu, Nan Zhang, Jiandong Niu, Mengna Zhang, Qinqin Zhang, Dan Chen, Yonghang Shi, Danni Chen, Kedi Liu, Xiaodi Zhang, Ning Li, Quan Fang
Summary: This study investigates the non-neuronal mechanisms involved in burn injury-induced pain (BIP) at the spinal cord level using a mouse model. The researchers found that both microglia and astrocytes are activated in response to burn injury, and the cytokines TNF and CXCL1 play important roles in pain hypersensitivity. The study suggests that targeting glial pathways could be a promising strategy for managing BIP.
BRAIN BEHAVIOR AND IMMUNITY
(2022)
Article
Cell Biology
Florencia Picech, Liliana DV. Sosa, Pablo A. Perez, Laura Cecenarro, Sergio R. Oms, Hugo A. Coca, Juan C. De Battista, Silvina Gutierrez, Jorge H. Mukdsi, Alicia I. Torres, Juan P. Petiti
Summary: The study showed that the inhibitory effects of OCT on somatotroph tumors can be enhanced by TGF-beta 1 in the presence of SSTR2, leading to decreased hormone secretion and proliferation.
JOURNAL OF CELLULAR PHYSIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Larissa Daniele Bobermin, Patricia Sesterheim, Daniele Schauren da Costa, Ester Rezena, Izaviany Schmitz, Amanda da Silva, Aline Daniel Moreira de Moraes, Diogo Onofre Souza, Angela T. S. Wyse, Guilhian Leipnitz, Carlos Alexandre Netto, Andre Quincozes-Santos, Carlos-Alberto Goncalves
Summary: In this study, the effects of simvastatin on inflammatory and functional parameters of primary cortical and hypothalamic astrocyte cultures obtained from IFN alpha/beta receptor knockout (IFN alpha/beta R-/-) mice were investigated. The results showed that simvastatin modulated cytokine production and release, as well as the expression of cytoprotective genes and functional parameters in astrocytes from different brain regions.
NEUROCHEMICAL RESEARCH
(2023)
Article
Cell Biology
Ji-an Wei, Linglin Liu, Xichen Song, Bilian Lin, Jing Cui, Lanzhi Luo, Yuchu Liu, Shihua Li, Xiaojiang Li, Kwok-Fai So, Sen Yan, Li Zhang
Summary: The aggregation of TDP-43 is associated with various neurodegenerative diseases, leading to microglial activation and neuronal loss. This study establishes a mouse model with overexpression of mutant TDP-43, which results in motor-learning deficits. Microglia are observed to approach parvalbumin interneurons, disrupting cortical excitatory-inhibitory balance. Activation of the complement pathway is found to induce microglial activity. Treadmill exercise prevents motor dysfunction by blocking the complement pathway through enhanced release of clusterin. These findings provide new insights into the mechanism of TDP-43-induced cortical deficits and the role of exercise training in disease intervention.
Article
Biochemistry & Molecular Biology
Yuki Kunioku, Maki Kimura, Takehito Ouchi, Kenichi Fukuda, Yoshiyuki Shibukawa
Summary: This study reports the extensive expression patterns of G(s) protein-coupled receptors in trigeminal ganglion neurons and their role in increasing intracellular cAMP levels. Activation of various receptors can increase intracellular cAMP concentration.
Article
Cell Biology
Sheng Zhang, Man Zhai, Yiwei Xu, Jiandong Han, Jiaxin Chen, Yucui Xiong, Shihua Pan, Qizheng Wang, Chunlai Yu, Zilong Rao, Qi Sun, Yufei Sui, Ke Fan, Heying Li, Wenjing Guo, Cuicui Liu, Ying Bai, Jing Zhou, Daping Quan, Xiao Zhang
Summary: Astrocytes, the most abundant and widespread glial cells in the central nervous system, play a crucial role in spinal cord injury repair. Decellularised spinal cord matrix (DSCM) has potential for SCI repair, but its specific mechanisms and niche alterations are not well understood. This study utilized single-cell RNA sequencing to investigate the regulatory mechanisms of DSCM on the glial niche in the neuro-glial-vascular unit.
CELL PROLIFERATION
(2023)
Article
Biochemistry & Molecular Biology
Markus Leo, Linda-Isabell Schmitt, Rebecca Steffen, Andrea Kutritz, Christoph Kleinschnitz, Tim Hagenacker
Summary: The study found that platinum-based chemotherapeutics activate spinal astrocytes and decrease the expression of excitatory amino acid transporter 1. The modulation of K-ir4.1 and EAAT1 proteins in astrocytes may be linked to the direct impact of the chemotherapy drugs, identifying spinal astrocytes as a potential target in the prevention and treatment of chemotherapy-induced neuropathy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Shoto Sasaki, Takayuki Negishi, Takamasa Tsuzuki, Kazunori Yukawa
Summary: This study reveals the toxicity mechanisms of methylmercury on rat cerebellar astrocytes, and identifies the involvement of reactive oxygen species (ROS) in the toxicity. Antioxidants have been tested to suppress the toxicity of methylmercury.
Article
Immunology
Shingo Yoshizaki, Tetsuya Tamaru, Masamitsu Hara, Ken Kijima, Masatake Tanaka, Dai-jiro Konno, Yoshihiro Matsumoto, Yasuharu Nakashima, Seiji Okada
Summary: The study demonstrated that beta 1Ab treatment could suppress the expression of TNF alpha in microglia and glial scars within the glial scar after SCI, and this alteration was associated with the role of fibronectin.
JOURNAL OF NEUROINFLAMMATION
(2021)
Article
Chemistry, Physical
Thuy Thi Thu Pham, Satish Jakkampudi, Ko Furukawa, Fung-Yu Cheng, Tzu-Chau Lin, Yoki Nakamura, Norimitsu Morioka, Manabu Abe
Summary: The study synthesized new NIR-2P-responsive chromophores with high yields and stability for physiological experiments. Different electron-donating groups significantly impacted the optical and chemical properties, affecting the two-photon uncaging efficiency as well.
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY A-CHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Yoki Nakamura, Ayako Fukuta, Keita Miyashita, Fang Fang Zhang, Dengli Wang, Keyue Liu, Hidenori Wake, Kazue Hisaoka-Nakashima, Masahiro Nishibori, Norimitsu Morioka
Summary: The study demonstrates that increased HMGB1 around the injured sciatic nerve may induce nociceptive hypersensitivity through the activation of spinal microglia.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Takahiro Kochi, Yoki Nakamura, Simeng Ma, Kazue Hisaoka-Nakashima, Dengli Wang, Keyue Liu, Hidenori Wake, Masahiro Nishibori, Masahiro Irifune, Norimitsu Morioka
Summary: The study found that blocking HMGB1 before nerve injury may prevent the onset of pain-related behaviors following orofacial surgery, possibly by inhibiting the activation of immune cells associated with nerve injury, both within the central nervous system and on peripheral nerves.
Article
Biochemistry & Molecular Biology
Norimitsu Morioka, Syun Kondo, Tomoyo Takimoto, Nozomi Tokunaga, Yoki Nakamura, Kazue Hisaoka-Nakashima
Summary: The study found that downregulation of Cx43 expression in the hippocampus may not be involved in the induction of depressive disorder in a neuropathic pain model, but may influence the efficacy of antidepressants.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Medicine, Research & Experimental
Fumiaki Sato, Yoki Nakamura, Simeng Ma, Takahiro Kochi, Kazue Hisaoka-Nakashima, Dengli Wang, Keyue Liu, Hidenori Wake, Masahiro Nishibori, Norimitsu Morioka
Summary: This study investigated the role of central HMGB1 in regulating nociceptive hypersensitivity in a mouse model of PD. The findings suggest that HMGB1 is involved in maintaining nociceptive symptoms in hemi-PD mice via spinal microglial activation, indicating its potential as a therapeutic target for pain associated with PD.
BIOMEDICINE & PHARMACOTHERAPY
(2022)
Article
Neurosciences
Chiori Onizuka, Masahiro Irifune, Akari Mukai, Yoshitaka Shimizu, Mitsuru Doi, Kana Oue, Mitsuhiro Yoshida, Takahiro Kochi, Eiji Imado, Takashi Kanematsu, Yoki Nakamura, Norimitsu Morioka, Yoshihiro Nakata, Norio Sakai
Summary: This study found that pentobarbital can inhibit neurogenic inflammation caused by surgery. By inhibiting the formation of cytokines and the release of substance P, pentobarbital may protect the nerves from inflammation after surgery.
NEUROSCIENCE LETTERS
(2022)
Article
Behavioral Sciences
Takahiro Kochi, Yoki Nakamura, Simeng Ma, Suzuna Uemoto, Kazue Hisaoka-Nakashima, Masahiro Irifune, Norimitsu Morioka
Summary: This study found that mirogabalin has a therapeutic effect on nerve injury-induced PTTN and does not cause sedation. This suggests that mirogabalin may be a valuable drug for treating PTTN.
BEHAVIOURAL BRAIN RESEARCH
(2022)
Article
Pharmacology & Pharmacy
Nozomi Tokunaga, Tomoyo Takimoto, Yoki Nakamura, Kazue Hisaoka-Nakashima, Norimitsu Morioka
Summary: This study investigates the relationship between Connexin 43 (Cx43) expression and induction of brain-derived neurotrophic factor(BDNF) production by antidepressants. The results show that downregulated Cx43 expression in depression patients might contribute to the therapeutic efficacy of antidepressants rather than the pathogenesis of depression. Furthermore, the study reveals that amitriptyline treatment potentiates BDNF expression in Cx43-knockdown astrocytes through LPA receptor(1/3) stimulation and subsequent activation of Src-ERK signaling.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Article
Neurosciences
Kazue Hisaoka-Nakashima, Kazuto Ohata, Natsuki Yoshimoto, Shintarou Tokuda, Nanako Yoshii, Yoki Nakamura, Dengli Wang, Keyue Liu, Hidenori Wake, Takayuki Yoshida, Yukio Ago, Kouichi Hashimoto, Masahiro Nishibori, Norimitsu Morioka
Summary: Clinical evidence suggests that cognitive impairment is a common comorbidity of chronic pain such as neuropathic pain, but the mechanism behind this impairment remains unclear. This study investigated the role of the proinflammatory molecule HMGB1 and microglial activation in cognitive impairment in mice with neuropathic pain. The findings suggest that blocking HMGB1 or microglial activation could be a novel approach to reducing cognitive impairment associated with neuropathic pain.
EXPERIMENTAL NEUROLOGY
(2022)
Article
Immunology
Kazue Hisaoka-Nakashima, Kodai Moriwaki, Natsuki Yoshimoto, Toshiki Yoshii, Yoki Nakamura, Yukio Ago, Norimitsu Morioka
Summary: Neuropathic pain causes severe pain and comorbidities such as cognitive impairment, which are not effectively treated with current analgesics. This study demonstrates the role of interleukin-6 (IL-6) in neuropathic pain and cognitive impairment. Blocking the IL-6 receptor improves cognitive impairment, while inhibiting IL-6 activity reduces allodynia.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Eiji Imado, Samnang Sun, Abrar Rizal Abawa, Takeru Tahara, Takahiro Kochi, Tran Ngoc Bao Huynh, Satoshi Asano, Shigeru Hasebe, Yoki Nakamura, Kazue Hisaoka-Nakashima, Yaichiro Kotake, Masahiro Irifune, Kazuhiro Tsuga, Kazuhiro Takuma, Norimitsu Morioka, Norikazu Kiguchi, Yukio Ago
Summary: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication and social interaction and the presence of restricted, repetitive behaviors. This study found that prenatal exposure to valproic acid (VPA) can cause increased tactile sensitivity and that spinal microglia play an important role in regulating nociceptive responses.
NEUROCHEMISTRY INTERNATIONAL
(2022)
Article
Biochemistry & Molecular Biology
Simeng Ma, Yoki Nakamura, Kazue Hisaoka-Nakashima, Norimitsu Morioka
Summary: Treatment options for diabetic neuropathy are limited, so the development of new therapeutic strategies is crucial. The role of receptor for advanced glycation end-products (RAGE) in diabetic neuropathy was investigated. The orally available small-molecule antagonist of RAGE, azeliragon, was found to improve mechanical hypersensitivity induced by streptozotocin (STZ) in mice. Repeat administration of azeliragon enhanced its antinociceptive effect significantly compared to single administration, and this effect was comparable to that of pregabalin. These findings suggest that RAGE may be an effective target for treating diabetic neuropathy.
NEUROCHEMISTRY INTERNATIONAL
(2023)
Article
Neurosciences
Natsuki Yoshimoto, Yoki Nakamura, Kazue Hisaoka-Nakashima, Norimitsu Morioka
Summary: Clinical evidence suggests that major depression is a common comorbidity of chronic pain, including neuropathic pain. The cellular basis for chronic pain-mediated major depression is still unclear. This study investigates the involvement of hippocampal mitochondrial dysfunction and neuroinflammation in anxiodepressive-like behaviors in mice with neuropathic pain.
EXPERIMENTAL NEUROLOGY
(2023)
Article
Pharmacology & Pharmacy
Hiroki Hashizume, Hatsune Motonari, Yoki Nakamura, Kazue Hisaoka-Nakashima, Norimitsu Morioka
Summary: Osteoarthritis (OA) is characterized by joint inflammation and degradation of articular cartilage matrix. This study investigated the regulation of inflammatory mediator expression in chondrocytes mediated by Toll-like receptor 4 (TLR4), a receptor for damage-associated molecular patterns (DAMPs), and found that TLR4 activation induced the expression of proinflammatory cytokines, matrix degradation enzymes, and inducible nitric oxide synthase in cultured rat chondrocytes. The study also identified the signaling molecules involved in the upregulated expression of these inflammatory mediators, providing potential new therapeutic targets for OA treatment strategies.
JOURNAL OF PHARMACOLOGICAL SCIENCES
(2023)
Article
Neurosciences
Norimitsu Morioka, Maho Tsuruta Nao Masuda, Kiichi Yamano, Manaya Nakano, Takahiro Kochi, Yoki Nakamura, Kazue Hisaoka-Nakashima
Summary: Microglial activity is critical in inducing central sensitization under chronic pain conditions. The nuclear receptor RORy plays a role in regulating inflammation-related gene transcription in immune cells, but its function in microglial activity and nociceptive transduction is not well understood.