Article
Cell Biology
Giselle Cheung, Oana Chever, Astrid Rollenhagen, Nicole Quenech'du, Pascal Ezan, Joachim H. R. Luebke, Nathalie Rouach
Summary: A study found that Connexin 43 (Cx43) is enriched in astroglial processes and plays a crucial role in synaptic transmission. It was discovered that Cx43 controls synaptic glutamate levels and allows for activity-dependent glutamine release to sustain normal synaptic transmission and cognition. However, its importance in synaptic vesicle release remains unanswered.
Article
Cell Biology
Ana R. Machado-Santos, Eduardo Loureiro-Campos, Patricia Patricio, Bruna Araujo, Nuno Dinis Alves, Antonio Mateus-Pinheiro, Joana Sofia Correia, Monica Morais, Joao M. Bessa, Nuno Sousa, Ana J. Rodrigues, Joao Filipe Oliveira, Luisa Pinto
Summary: This study investigates the importance of de novo generated astrocytes in the pathophysiology and treatment of depression, revealing the potential of newborn astrocytes as therapeutic targets for future depression treatments.
Review
Chemistry, Multidisciplinary
Ning-ning Zhang, Yi Zhang, Zhen-zhen Wang, Nai-hong Chen
Summary: This review summarizes the role of connexin 43 (Cx43) in the pathogenesis of depression. Studies have shown that dysfunction of Cx43 is associated with depression and regulating the expression of Cx43 can influence depressive behaviors. The review also discusses the effects of antidepressants on Cx43.
ACTA PHARMACOLOGICA SINICA
(2022)
Article
Neurosciences
Brunno Rocha Levone, John F. Cryan, Olivia F. O'Leary
Summary: Studies have shown that different sub-regions of the hippocampus play distinct roles in stress responses, with the intermediate hippocampus playing a predominant role in stress-induced social avoidance, and the ventral sub-region having a predominant role in active coping behaviors and antidepressant-like behavior.
Article
Biochemistry & Molecular Biology
Li-Li Luo, Jian-Wu Wang, Xiao-Lan Yin, Xiao-Yong Chen, Xia-Fei Zhang, Zu-Cheng Ye
Summary: Neuropathic pain (NP) is a chronic disease caused by nervous system damage. Connexin 43 (Cx43), expressed by astrocytes, is significantly increased in NP. However, the roles and mechanisms of Cx43 in NP are still largely unknown, while microglia activation is commonly considered a key factor in NP. In this study, Cx43 deletion was found to alleviate SNI-induced NP and suppress c-Fos expression in the spinal cord. Cx43 deletion also resulted in reduced microglia activation. These findings suggest that astrocyte Cx43 may play a significant role in regulating microglial activation and NP.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Immunology
Wansu Qiu, Kimberly A. Go, Yanhua Wen, Paula Duarte-Guterman, Rand S. Eid, Liisa A. M. Galea
Summary: Untreated perinatal depression can have severe consequences for the mother and her children, with the efficacy and safety of pharmacological antidepressants questioned. Maternal SSRI exposure may impact the neuroinflammatory profile of adult offspring, and perinatal SSRI exposure has been linked to increased risk of autism spectrum disorder in children. Further research on oxytocin as a treatment for ASD and TriozanTM as a method of crossing the blood-brain barrier is ongoing.
BRAIN BEHAVIOR AND IMMUNITY
(2021)
Article
Neurosciences
Ana R. Machado-Santos, Nuno D. Alves, Bruna Araujo, Joana S. Correia, Patricia Patricio, Antonio Mateus-Pinheiro, Eduardo Loureiro-Campos, Joao M. Bessa, Nuno Sousa, Luisa Pinto
Summary: Astrocytes play crucial roles in the central nervous system, interacting closely with neurons to modulate brain function. Studies have shown numerical and morphological changes in astrocytes in the hippocampus of both Major Depressive Disorder patients and animal models of depression. Antidepressants such as fluoxetine and imipramine can modulate astrocytic alterations, preventing long-term effects of recurrent stress exposure.
Review
Biochemistry & Molecular Biology
Yan-Jun Zong, Xiao-Zhou Liu, Lei Tu, Yu Sun
Summary: This review discusses the contribution of the connexin gene family to hearing loss, focusing on the GJB2, GJB6, and GJA1 genes. Mutations in these genes can lead to comprehensive or non-comprehensive genetic deafness in newborns. The precise regulation of connexin biosynthesis, structural composition, and degradation is crucial for proper functioning of gap junctions. This review provides insights into the etiological principles of connexin mutations and offers potential therapeutic strategies for hereditary deafness.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Robert J. McDonald, Nancy S. Hong, Jan S. Trow, Chelsea Kaupp, R. J. Balog, London Gokarn, Erin A. Falkenberg, Keiko J. McCreary, Nasrin Soltanpour, Carter Witbeck, Aimee McKenna, Gerlinde A. S. Metz
Summary: Prenatal experiences can have lasting effects on offspring physiology and behavior. Different forms of prenatal stress can impair learning and memory function in adults and increase the risk of anxiety and depression. This study focused on the effects of maternal stress induced by social isolation on cognitive functions in adult offspring, specifically spatial, stimulus-response, and emotional learning and memory.
SCIENTIFIC REPORTS
(2023)
Article
Medicine, Research & Experimental
Huiqin Wang, Xueying Yang, Huaqing Lai, Yang Sun, Xu Yan, Qidi Ai, Meiyu Lin, Songwei Yang, Yantao Yang, Shifeng Chu, Zhenzhen Wang, Naihong Chen
Summary: Hypericin repaired the dysfunction of gap junctions in the chronic unpredictable stress (CUS) rat model of depression. While hypericin showed potential for treating depression in in vivo experiments, it failed to demonstrate antidepressant benefits in cell experiments. This study suggests that gap junctional function may be a novel therapeutic target for hypericin in the treatment of depression.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Biochemistry & Molecular Biology
Mohamed Yassine El Brouzi, Mouloud Lamtai, Oussama Zghari, Sihame Ouakki, Ibrahim Azizoun, Aboubaker El Hessni, Abdelhalem Mesfioui, Ali Ouichou
Summary: The study focused on how male Wistar rats' affective and cognitive behaviors were affected by exposure to nickel chloride, and how oxidative stress played a role in these effects. Results showed that nickel chloride caused anxiety-like and depressive-like behaviors, as well as memory and spatial learning disorders in rats. Additionally, oxidative stress markers in the hippocampus were also affected by the exposure to nickel chloride.
BIOLOGICAL TRACE ELEMENT RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Fernando Cruz-Mendoza, Sonia Luquin, Joaquin Garcia-Estrada, David Fernandez-Quezada, Fernando Jauregui-Huerta
Summary: This study investigated the effects of acoustic stress on hippocampal proliferation and glial cytoarchitecture in adult male rats using environmental noise as a stress model. The results showed abnormal cellular proliferation in the hippocampus after 21 days of noise exposure, with an inverse effect on the proliferation ratios of astrocytes and microglia. Both cell lineages also displayed atrophic morphologies with fewer processes and lower densities in the noise-stressed animals. These findings suggest that stress not only affects neurogenesis and neuronal death in the hippocampus, but also the proliferation ratio, cell density, and morphology of glial cells, potentially triggering an inflammatory-like response that compromises their homeostatic and repair functions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Shuhei Fukuda, Masako Akiyama, Yuki Niki, Risa Kawatsura, Hiroyuki Harada, Ken-ichi Nakahama
Summary: The study revealed that miRNAs produced by normal cells can be transferred to cancer cells via connexin 43, inhibiting tumor migration and invasion.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Haya Hussain, Shujaat Ahmad, Syed Wadood Ali Shah, Abid Ullah, Mazen Almehmadi, Osama Abdulaziz, Mamdouh Allahyani, Ahad Amer Alsaiari, Mustafa Halawi, Edrous Alamer
Summary: This study found that curcumin analogues C2 and C3 have potential as antistress and antidepressant agents. They exhibited significant reduction in writhes and immobility times, as well as enhanced antioxidant enzyme activity in the hippocampus.
Review
Biochemistry & Molecular Biology
Oleg Dolotov, Ludmila S. Inozemtseva, Nikolay F. Myasoedov, Igor A. Grivennikov
Summary: Neurodegenerative diseases and depression have complex and poorly understood physiopathology. Astrocytes play a key role in both normal and pathological neuronal functioning. Stress is an important factor in the development of brain disorders and can affect astrocyte function, leading to depression and Alzheimer's disease. The involvement of astrocyte dysfunction in these disorders suggests that astrocytes could be a promising target for treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Audrey M. Thiebaut, Izaskun Buendia, Vanessa Ginet, Eloise Lemarchand, Mehdi Boutagouga Boudjadja, Yannick Hommet, Laurent Lebouvier, Charlotte Lechevallier, Mike Maillasson, Elodie Hedou, Nicole Deglon, Franck Oury, Marina Rubio, Joan Montaner, Julien Puyal, Denis Vivien, Benoit D. Roussel
Summary: Cerebral ischemia induces harmful autophagy in neurons, while PLAT/tPA can mediate neuroprotection by decreasing autophagy levels. The research discovered that PLAT/tPA degrades IGFBP3 to increase the bioavailability of IGF1, leading to the activation of neuroprotective pathways.
Article
Biotechnology & Applied Microbiology
Elodie Leroux, Romain Perbet, Raphaelle Caillierez, Kevin Richetin, Sarah Lieger, Jeanne Espourteille, Thomas Bouillet, Severine Begard, Clement Danis, Anne Loyens, Nicolas Toni, Nicole Deglon, Vincent Deramecourt, Susanna Schraen-Maschke, Luc Buee, Morvane Colin
Summary: Tauopathies are neurodegenerative diseases characterized by tau inclusions in brain cells. This study suggests that extracellular vesicles (EVs) may play a role in the prion-like propagation of tau pathology among different tauopathies. The researchers isolated EVs from different brain regions in various tauopathies and found that EVs from Alzheimer's disease patients contained pathological tau species that could induce tau lesions in vivo. These findings have implications for diagnostic and therapeutic strategies.
Review
Endocrinology & Metabolism
Stephanie Fulton, Lea Decarie-Spain, Xavier Fioramonti, Bruno Guiard, Shingo Nakajima
Summary: Obesity exacerbates the incidence of depression and anxiety, mainly due to poor diet and lack of physical activity, resulting in metabolic and vascular dysfunction that affects neural status and mood.
TRENDS IN ENDOCRINOLOGY AND METABOLISM
(2022)
Article
Nutrition & Dietetics
Laurent Brondel, Didier Quilliot, Thomas Mouillot, Naim Akhtar Khan, Philip Bastable, Vincent Boggio, Corinne Leloup, Luc Penicaud
Summary: Obesity is the result of an alteration in the homeostatic feedback of energy balance, leading to a temporary or prolonged positive energy balance. Food plays a key role in reward-based energy intake, and an alteration in the brain reward system may contribute to the development of obesity by increasing the attractiveness and consumption of fat-rich foods. Understanding this altered reward system may have implications for the diagnosis, management, and treatment of obesity.
Correction
Biochemistry & Molecular Biology
Morgane Humbel, Mergim Ramosaj, Virginie Zimmer, Sara Regio, Ludiwine Aeby, Sylvain Moser, Alexia Boizot, Melanie Sipion, Maria Rey, Nicole Deglon
Article
Biotechnology & Applied Microbiology
Margareta Rybarikova, Amanda Almacellas-Barbanoj, Stephanie Schorge, Nicole Deglon
Summary: The recent success of the first central nervous system gene therapies has revitalized gene therapy research and increased clinical trials for neurologic diseases caused by genetic mutations. Advances in technology have expanded the scope of treatment applications and bridged the gap between major global health issues and gene therapy development.
HUMAN GENE THERAPY
(2022)
Article
Neurosciences
Francesco Petrelli, Tamara Zehnder, Anthony Laugeray, Sarah Mondoloni, Corrado Cali, Luca Pucci, Alicia Molinero Perez, Bianca Maria Bondiolotti, Eva De Oliveira Figueiredo, Glenn Dallerac, Nicole Deglon, Bruno Giros, Lorenzo Magrassi, Jean-Pierre Mothet, Manuel Mameli, Linda D. Simmler, Paola Bezzi
Summary: This study investigates the relationship between VMAT2 in astrocytes and the regulation of DA levels, finding that impairment of astrocytic control of DA leads to reduced DA levels, excessive grooming, and compulsive repetitive behaviors. The expression of VMAT2 in human PFC astrocytes validates the translational relevance of these findings.
BIOLOGICAL PSYCHIATRY
(2023)
Article
Immunology
Evangelos Konstantinidis, Benjamin Portal, Tobias Mothes, Chiara Beretta, Maria Lindskog, Anna Erlandsson
Summary: This study reveals that astrocytes in Alzheimer's disease (AD) are not only associated with the pathology but also play a crucial role in maintaining brain homeostasis and synaptic function. The accumulation of aggregated amyloid-beta (A beta) in astrocytes affects their interaction with neurons, leading to synaptic dysfunction and neuronal apoptosis. These findings are important for understanding the involvement of astrocytes in AD-related synaptic dysfunction.
JOURNAL OF NEUROINFLAMMATION
(2023)
Article
Medicine, Research & Experimental
Fabio Duarte, Mergim Ramosaj, Ed Hasanovic, Sara Regio, Melanie Sipion, Maria Rey, Nicole Deglon
Summary: One obstacle to developing gene therapies for the central nervous system is the lack of workflows for quantifying transduction efficiency and predicting therapeutic potential. In this study, the researchers integrated data from a brain cell atlas with quantification of transduced cells to predict transduction efficiency in multiple brain regions. They validated their pipeline in gene editing experiments and demonstrated its power to predict transduction efficiency and therapeutic potential in the central nervous system.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2023)
Article
Cell Biology
Romain Perbet, Valentin Zufferey, Elodie Leroux, Enea Parietti, Jeanne Espourteille, Lucas Culebras, Sylvain Perriot, Renaud Du Pasquier, Severine Begard, Vincent Deramecourt, Nicole Deglon, Nicolas Toni, Luc Buee, Morvane Colin, Kevin Richetin
Summary: Tau protein accumulation in astrocytes is involved in neurodegenerative disorders. The origins of 3R and 4R isoforms of tau in astrocytes remain unclear. This study demonstrates that neurons with accumulated 3R or 4R tau have the ability to transfer tau to astrocytes through extracellular vesicles (EVs). Tau-containing EVs disrupt the mitochondrial system of astrocytes and the damage is more severe with 3R tau-containing EVs. EVs from the brain fluid of tauopathy patients also affect mitochondrial function in astrocytes derived from human induced pluripotent stem cells (iPSCs).
Editorial Material
Endocrinology & Metabolism
Xavier Fioramonti
Article
Biotechnology & Applied Microbiology
Fabio Duarte, Gabriel Vachey, Nicholas S. Caron, Melanie Sipion, Maria Rey, Anselme L. Perrier, Michael R. Hayden, Nicole Deglon
Summary: Huntington's disease is a fatal neurodegenerative disorder that can be treated by inactivating the mutated HTT gene. One approach to selectively inactivate the mutant allele is by using the CRISPR/Cas9 system to remove the first exon of the mutated HTT. However, the frequency of deletion events is still uncertain.
HUMAN GENE THERAPY
(2023)
Article
Psychiatry
Basile Coutens, Camille Lejards, Guillaume Bouisset, Laure Verret, Claire Rampon, Bruno P. Guiard
Summary: Mood disorders are associated with overactivity of the hypothalamic-pituitary-adrenal axis due to decreased inhibitory feedback from the hippocampus. Antidepressants can regulate the excitatory/inhibitory balance of the hippocampus to restore effective inhibition of this stress axis. Non-pharmacological strategies, such as environmental enrichment, can improve therapeutic outcome in depressed patients, but it is unknown if they can reduce the delay of action of antidepressants.
TRANSLATIONAL PSYCHIATRY
(2023)
Meeting Abstract
Biotechnology & Applied Microbiology
F. Duarte, G. Vachey, M. Ramosaj, S. Regio, M. Sipion, M. Rey, N. Deglon
HUMAN GENE THERAPY
(2022)
Article
Neurosciences
Fares Sayegh, Laurie Herraiz, Morgane Colom, Sebastien Lopez, Claire Rampon, Lionel Dahan
Summary: Dopamine plays a role in encoding memories and can encode the rewarding/aversive value of stimuli or trigger contextual learning as a novelty signal. In this study, the dopamine D1/5R antagonist SCH23390 was shown to impair contextual fear conditioning and tone-shock association following intraperitoneal injection, while intrahippocampal injection only affected contextual fear conditioning. Using the context pre-exposure facilitation effect test, it was found that SCH23390 blocked the encoding of the context during the pre-exposure phase. This provides additional evidence for the involvement of dopamine in encoding conjunctive representations of new contexts.