Review
Biochemistry & Molecular Biology
Alice McDouall, Kelly Q. Zhou, Laura Bennet, Colin R. Green, Alistair J. Gunn, Joanne O. Davidson
Summary: Perinatal brain injury, caused by hypoxia-ischemia and/or infection/inflammation, is a major cause of disability. Despite the effectiveness of therapeutic hypothermia, additional interventions are needed as nearly half of the infants still have adverse outcomes. Recent studies have shown that brain injury spreads over time from the initial site to previously unaffected regions, partly due to the opening of connexin hemichannels and pannexin channels. Blockade of these channels has demonstrated neuroprotective effects in animal models, suggesting their potential as targeted interventions in combination or separate from therapeutic hypothermia.
Article
Pharmacology & Pharmacy
Di Yang, Mengyuan Chen, Sijia Yang, Furong Deng, Xinbiao Guo
Summary: Connexin hemichannels and pannexin channels are transmembrane channels that facilitate the exchange of ions and molecules between intra- and extracellular compartments. However, their excessive opening can disrupt cell homeostasis and function due to the permeation of toxic substances and essential metabolites. This review explores the activation of these channels by external stimuli and their involvement in toxicological pathways, including inflammation and oxidative damage.
Article
Neurosciences
Qiqian Wang, Shenquan Liu
Summary: This study demonstrates that the passive transmembrane ion transport model applies to hemichannels and non-junctional plasma membranes, leading to the establishment of a gap junctional channel model. Numerical simulations were used to study homotypic and heterotypic gap junctions formed by connexins, innexins, and pannexins, shedding light on the physiology of hemichannels and gap junctions.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Review
Biochemistry & Molecular Biology
Ryo Yamasaki
Summary: Connexins form gap junctions that allow the movement of bioactive molecules between cells and play crucial roles in neurological dysfunctions. Modulating connexin hemichannels could be a promising therapeutic approach for treating these disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Raf Van Campenhout, Ana Rita Gomes, Timo W. M. De Groof, Serge Muyldermans, Nick Devoogdt, Mathieu Vinken
Summary: Gap junctions and connexin hemichannels play different roles in intercellular and extracellular communication, with the former maintaining homeostasis and the latter being associated with the onset and spread of disease by mediating messenger transport that fuels inflammation and cell death in various diseases. The present review discusses the mechanisms involved in the activation of connexin hemichannels during pathology.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Neurosciences
Xiaomin Huang, Yixun Su, Nan Wang, Hui Li, Zhigang Li, Guowei Yin, Hui Chen, Jianqin Niu, Chenju Yi
Summary: Astrocytes play a crucial role in maintaining the normal functions of the Central Nervous System (CNS). During neurodegenerative diseases, alterations in astrocytic connexin expression and function can affect disease progression by impacting neuronal function and survival. Targeting connexins may be a plausible therapeutic strategy for managing these neurodegenerative diseases.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2021)
Article
Genetics & Heredity
Ivan Mizdrak, Maja Mizdrak, Anita Racetin, Braco Boskovic, Benjamin Benzon, Merica Glavina Durdov, Katarina Vukojevic, Natalija Filipovic
Summary: This study analyzed the expression pattern of connexins (Cx) 37, 40 and 45, pannexin1 (Panx1) and vimentin in squamous cell carcinoma (LSCC) and their correlation with tumor grade and outcome. The results showed significant differences in the expression of Cx37, Cx40, and Panx1 between cancer and normal mucosa, and between different grades. Lower Panx1 expression and higher vimentin expression were found to be prognostic factors for regional metastatic disease. Lower expression of Cx37 and Cx40 was associated with disease recurrence after follow-up.
Review
Biochemistry & Molecular Biology
Joon Ho Seo, Miloni S. Dalal, Jorge E. Contreras
Summary: Neuroinflammation is a key feature of various CNS diseases, involving the release of pro-inflammatory molecules like ATP and the pivotal role of Panx1 channels in the inflammatory response.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Neurosciences
Jianhui Liu, Xuanran Feng, Yi Wang, Xiaohuan Xia, Jialin C. Zheng
Summary: Astrocytes, the most abundant glial cells in the brain, have been found to be GABAceptive and play a role in regulating neurotransmission and brain function by capturing and releasing GABA.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Cardiac & Cardiovascular Systems
Alessio Lissoni, Paco Hulpiau, Tania Martins-Marques, Nan Wang, Geert Bultynck, Rainer Schulz, Katja Witschas, Henrique Girao, Maarten De Smet, Luc Leybaert
Summary: The research revealed that the activation of ryanodine receptors (RyRs) triggers unitary currents with a single-channel conductance of around 220 pS, which are significantly reduced by knocking down connexin 43 (Cx43). The study also showed that both RyR activation and intracellular Ca2+ elevation are necessary for the opening of Cx43 hemichannels.
CARDIOVASCULAR RESEARCH
(2021)
Article
Neurosciences
Alice McDouall, Guido Wassink, Sumudu Ranasinghe, Kelly Q. Zhou, Rashika N. Karunasinghe, Justin M. Dean, Joanne O. Davidson
Summary: This study found that blocking connexin 43 hemichannels can attenuate brain injury and promote neurodevelopment in infants with mild hypoxic-ischemic encephalopathy, without causing hypothermia.
EXPERIMENTAL NEUROLOGY
(2024)
Review
Cell Biology
Lan Lei, Ya-Ting Wang, Die Hu, Cong Gai, Yi Zhang
Summary: Major depression disorder (MDD) is a neuropsychiatric disorder associated with high suicide and disability rates. The pathology of MDD is related to astrocyte dysfunction, specifically the expression and function of connexin 43 (Cx43). Neuroinflammation is also a key factor in depression pathology, and Cx43 is believed to be involved in neuroinflammation-related depression. The specific mechanism of Cx43-mediated functions in neuroinflammation-related depression pathology is still unknown.
CELLULAR AND MOLECULAR NEUROBIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Kyung Hee Lee, Myeounghoon Cha, Bae Hwan Lee
Summary: This article discusses the role of glia in protecting neurons from oxidative injury and maintaining antioxidant defense mechanisms in the brain, as well as the essential crosstalk between glia and neurons to maintain redox balance for protection against oxidative stress.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Yi Wang, Jie Li, Meng-Yue Wang, Zhi-Yong Pan, Zhi-Qiang Li, Ze-Fen Wang
Summary: Neuronal activity is closely linked to energy metabolism, and the mechanisms underlying inflammation-induced neuronal injury are not fully understood. This study revealed that chronic inflammation affects the levels and metabolism of lactate in astrocytes and neurons, leading to increased lactate supply to neurons but impaired lactate oxidation. Additionally, chronic inflammation disrupts the neuronal cytoskeleton.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Akshata A. Almad, Arens Taga, Jessica Joseph, Sarah K. Gross, Connor Welsh, Aneesh Patankar, Jean -Philippe Richard, Khalil Rust, Aayush Pokharel, Caroline Plott, Mauricio Lillo, Raha Dastgheyb, Kevin Eggan, Norman Haughey, Jorge E. Contreras, Nicholas J. Maragakis
Summary: This study demonstrates that Cx43 hemichannels play a role in the progression of ALS by mediating astrocyte communication and that blocking these channels can provide neuroprotection for motor neurons. Additionally, Cx43 expression is up-regulated in ALS patients' tissue and cerebrospinal fluid.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Neurosciences
Valeria C. Labra, Cristian A. Santibanez, Rosario Gajardo-Gomez, Esteban F. Diaz, Gonzalo Gomez, Juan A. Orellana
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2018)
Correction
Neurosciences
Cheril Tapia-Rojas, Francisco J. Carvajal, Rodrigo G. Mira, Camila Arce, Jose Manuel Lerma-Cabrera, Juan A. Orellana, Waldo Cerpa, Rodrigo A. Quintanilla
MOLECULAR NEUROBIOLOGY
(2018)
Review
Neurosciences
Sebastian Vejar, Juan E. Oyarzun, Mauricio A. Retamal, Fernando C. Ortiz, Juan A. Orellana
FRONTIERS IN CELLULAR NEUROSCIENCE
(2019)
Article
Neurosciences
Esteban F. Diaz, Valeria C. Labra, Tanhia F. Alvear, Luis A. Mellado, Carla A. Inostroza, Juan E. Oyarzun, Nicole Salgado, Rodrigo A. Quintanilla, Juan A. Orellana
Article
Neurosciences
Carolina E. Chavez, Juan E. Oyarzun, Beatriz C. Avendano, Luis A. Mellado, Carla A. Inostroza, Tanhia F. Alvear, Juan A. Orellana
FRONTIERS IN CELLULAR NEUROSCIENCE
(2019)
Article
Pharmacology & Pharmacy
Osvaldo Flores-Bastias, Gonzalo Gomez, Juan A. Orellana, Eduardo Karahanian
CURRENT PHARMACEUTICAL DESIGN
(2019)
Article
Biochemistry & Molecular Biology
Rosario Gajardo-Gomez, Cristian A. Santibanez, Valeria C. Labra, Gonzalo Gomez, Eliseo A. Eugenin, Juan A. Orellana
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Biochemistry & Molecular Biology
Juan C. Saez, Anibal A. Vargas, Diego E. Hernandez, Fernando C. Ortiz, Christian Giaume, Juan A. Orellana
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Editorial Material
Pharmacology & Pharmacy
Lorenzo Di Cesare Mannelli, Stefania Ceruti, Juan A. Orellana
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Juan Prieto-Villalobos, Tanhia F. Alvear, Andres Liberona, Claudia M. Lucero, Claudio J. Martinez-Araya, Javiera Balmazabal, Carla A. Inostroza, Gigliola Ramirez, Gonzalo I. Gomez, Juan A. Orellana
Summary: Maternal inflammation can lead to later-in-life brain abnormalities in offspring, affecting the survival and support of neurons, and increasing the risk of neurological disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Sergio Linsambarth, Francisco J. Carvajal, Rodrigo Moraga-Amaro, Luis Mendez, Giovanni Tamburini, Ivanka Jimenez, Daniel Antonio Verdugo, Gonzalo Gomez, Nur Jury, Pablo Martinez, Brigitte van Zundert, Lorena Varela-Nallar, Mauricio A. Retamal, Claire Martin, Guillermo A. Altenberg, Mariana C. Fiori, Waldo Cerpa, Juan A. Orellana, Jimmy Stehberg
Summary: Astrocytes release glutamate and D-serine through Cx43 hemichannels to modulate synaptic activity, which is crucial for fear memory consolidation.
Review
Biochemistry & Molecular Biology
Paloma P. Maldonado, Coram Guevara, Margrethe A. Olesen, Juan Andres Orellana, Rodrigo A. Quintanilla, Fernando C. Ortiz
Summary: This article discusses the role of mitochondrial dysfunction in the progression of multiple sclerosis (MS), focusing on the potential role of Nrf2 signaling in neuroinflammation and neurodegeneration. The authors propose that Nrf2 dysfunction affects the bioenergetics, antioxidant defense, and energy supply provided by glial cells to neurons.
Review
Biochemistry & Molecular Biology
Claudia M. Lucero, Juan Prieto-Villalobos, Lucas Marambio-Ruiz, Javiera Balmazabal, Tanhia F. Alvear, Matias Vega, Paola Barra, Mauricio A. Retamal, Juan A. Orellana, Gonzalo Gomez
Summary: Hypertension is a common risk factor for chronic cardiovascular diseases and hypertensive nephropathy. AngII-mediated abnormal intracellular Ca2+([Ca2+]i) signaling and the opening of connexins or pannexins channels contribute to renal damage.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Ivanka Jimenez-Dinamarca, Rachel Reyes-Lizana, Yordan Lemunao-Inostroza, Kevin Cardenas, Raimundo Castro-Lazo, Francisca Pena, Claudia M. Lucero, Juan Prieto-Villalobos, Mauricio Antonio Retamal, Juan Andres Orellana, Jimmy Stehberg
Summary: GABA plays a crucial role in regulating the excitatory/inhibitory balance in the brain by affecting the activity of neurons and astrocytes through different GABA receptors. This study specifically focuses on how GABA influences astroglial Cx43 hemichannel activity and its release of glutamate and ATP, providing insights into potential mechanisms underlying psychiatric disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biology
Juan Prieto-Villalobos, Claudia M. Lucero, Maximiliano Rovegno, Gonzalo I. Gomez, Mauricio A. Retamal, Juan A. Orellana
Summary: This study found that the spike protein S1 of SARS-CoV-2 can increase the activity of Cx43 hemichannels, potentially leading to cellular dysfunction and damage observed in COVID-19 patients. Therefore, investigating Cx43 hemichannels may provide insights for developing therapies against viral infection.
BIOLOGICAL RESEARCH
(2023)
Article
Neurosciences
Yang He, Jun Tang, Meng Zhang, Junjie Ying, Dezhi Mu
Summary: This study investigated the protective effects and mechanisms of human placenta derived mesenchymal stem cells (hPMSCs) transplantation in a rat model of hypoxic-ischemic encephalopathy (HIE). The results showed that hPMSCs transplantation reduced apoptosis and improved long-term neurological prognosis. Furthermore, the downregulation of Sema 3A/NRP-1 expression and activation of the PI3K/Akt/mTOR signaling pathway played a key role in the protective effects of hPMSCs.
Article
Neurosciences
Emily L. Isenstein, Edward G. Freedman, Jiayi Xu, Ian A. DeAndrea-Lazarus, John J. Foxe
Summary: This study evaluated electrophysiological discrimination of parametric somatosensory stimuli in healthy young adults to understand how the brain processes the duration of tactile information. The results showed that participants did not electrophysiologically discriminate between 100 and 115 ms, but they exhibited distinct electrophysiological responses when the deviant stimuli were 130, 145, and 160 ms. These findings contribute to a better understanding of tactile sensitivity in different clinical conditions.
Article
Neurosciences
Juliana R. Souza, Ludmila Lima-Silveira, Daniela Accorsi-Mendonca, Benedito H. Machado
Summary: This study demonstrates that A2A receptors play a crucial role in modulating synaptic transmission in the NTS neurons and are required for the enhancement of glutamatergic transmission observed under short-term sustained hypoxia conditions.
Article
Neurosciences
Miki Hashizume, Rina Ito, Rie Suge, Yasushi Hojo, Gen Murakami, Takayuki Murakoshi
Summary: The basolateral amygdaloid complex (BLA) is closely involved in the formation of emotional memories, including both aversive memory and contextual fear memory. Acute sleep deprivation (SD) disrupts the acquisition of tone-associated fear memory in juvenile rats, but has no significant effect on contextual fear memory. Slow network oscillation in the amygdala contributes to the formation of amygdala-dependent fear memory in relation to sleep.
Article
Neurosciences
Qunxian Wang, Shipeng Guo, Dongjie Hu, Xiangjun Dong, Zijun Meng, Yanshuang Jiang, Zijuan Feng, Weihui Zhou, Weihong Song
Summary: GSDME plays a crucial role in the pathogenesis of Alzheimer's disease by regulating the switch from apoptosis to pyroptosis and participating in neuroinflammatory response. Knockdown of GSDME has been shown to improve cognitive impairments, indicating that GSDME could be a therapeutic target for Alzheimer's disease.