Review
Neurosciences
Ananth Prasad Burada, Rajesh Vinnakota, Bertrand Lambolez, Ludovic Tricoire, Janesh Kumar
Summary: Enigmatic orphan glutamate delta receptors (GluD) are a type of ionotropic glutamate receptors (iGluRs) that do not bind glutamate or evoke currents when binding glycine and D-serine. They are believed to function as structural proteins that facilitate synapse formation, maturation, and maintenance in the hippocampus and cerebellum. Recent research suggests that GluD receptors have interactions with metabotropic glutamate receptors (mGlus) and are gated by their activation, with new tools and structures helping to define their role in synaptic physiology.
Review
Pharmacology & Pharmacy
Ananth Prasad Burada, Rajesh Vinnakota, Pratibha Bharti, Priyanka Dutta, Neelima Dubey, Janesh Kumar
Summary: GluD receptors are a subfamily of ionotropic glutamate receptors that play a crucial role in synapse formation, maturation, and maintenance of central nervous system functions. Despite the lack of knowledge about their endogenous ligands, significant discoveries have been made regarding their role in mediating trans-synaptic interactions and their unique non-swapped architecture. Additionally, the prospect of GluD ionotropic activity being regulated by direct interaction with metabotropic glutamate receptors is exciting.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Neurosciences
Prachi Ojha, Subhajit Pal, Samarjit Bhattacharyya
Summary: Norbin protein plays a critical role in the internalization process of Group I mGluRs and may be associated with mGluR-mediated synaptic plasticity.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Neurosciences
Anna Bodzeta, Nicky Scheefhals, Harold D. MacGillavry
Summary: The various functions of glutamate in the brain are mediated by ionotropic and metabotropic glutamate receptors, which modulate synaptic transmission and plasticity. mGluRs play roles at both presynaptic and postsynaptic sites, acting as essential signal integrators that couple mechanisms of transmission and plasticity.
Article
Neurosciences
Ahmed H. Al-Amri, Paul Armstrong, Mascia Amici, Clemence Ligneul, James Rouse, Mohammed E. El-Asrag, Andreea Pantiru, Valerie E. Vancollie, Hannah W. Y. Ng, Jennifer A. Ogbeta, Kirstie Goodchild, Jacob Ellegood, Christopher J. Lelliott, Jonathan G. L. Mullins, Amanda Bretman, Ruslan Al-Ali, Christian Beetz, Lihadh Al-Gazali, Aisha Al Shamsi, Jason P. Lerch, Jack R. Mellor, Abeer Al Sayegh, Manir Ali, Chris F. Inglehearn, Steven J. Clapcote
Summary: This study demonstrates the involvement of homozygous loss-of-function mutations in PDZD8 in a neurodevelopmental cognitive disorder. Model organisms with manipulation of the orthologous gene replicate aspects of the human phenotype and suggest plausible pathophysiological mechanisms centered on disrupted brain development and synaptic function.
BIOLOGICAL PSYCHIATRY
(2022)
Article
Neurosciences
G. Martella, P. Bonsi, P. Imbriani, G. Sciamanna, H. Nguyen, L. Yu-Taeger, M. Schneider, S. M. Poli, R. Lutjens, A. Pisani
Summary: Impairment of long-term synaptic plasticity is a unique endophenotype of certain forms of dystonia. Broad-spectrum antimuscarinic drugs and negative allosteric modulators of metabotropic glutamate receptor subtypes may be potential therapeutic options for dystonia treatment. The findings suggest common signaling pathway dysfunction among distinct dystonia genes and indicate the potential of dipraglurant as a novel therapeutic agent for this debilitating disorder.
Article
Biochemistry & Molecular Biology
Jiyong Meng, Chanjuan Xu, Pierre-Andre Lafon, Salome Roux, Michael Mathieu, Rui Zhou, Pauline Scholler, Emilie Blanc, Jerome A. J. Becker, Julie Le Merrer, Javier Gonzalez-Maeso, Patrick Chames, Jianfeng Liu, Jean-Philippe Pin, Philippe Rondard
Summary: This study presents a method for determining the subunit composition of endogenous cell surface protein complexes using nanobody-based sensors. The authors demonstrate the presence and activation of GPCR mGlu2 and mGlu4 dimers in mouse brain samples, and reveal the prevalence of mGlu2-mGlu4 heterodimers in addition to mGlu2 and mGlu4 homodimers.
NATURE CHEMICAL BIOLOGY
(2022)
Article
Cell Biology
Kexin Li, Meng Lu, Mengxu Cui, Xiaoming Wang, Yang Zheng
Summary: This study investigated the changes in NAAG, Glu, and mGluR expression, as well as the effects on synaptic plasticity in the brain after HI injury. The results showed an increase in NAAG and mGluR3 expression levels after HI, with a correlation between Glu content and mGluR1/mGluR5 expression. NAAG was found to maintain cortical synaptic plasticity and neurotransmitter homeostasis. Hibernated NAAG levels after 12-24 h of HI injury were associated with mGluR3 receptor expression, thus indicating their role in preserving synaptic function.
CELL COMMUNICATION AND SIGNALING
(2022)
Review
Clinical Neurology
Roghayeh Mozafari, Saeideh Karimi-Haghighi, Mojdeh Fattahi, Peter Kalivas, Abbas Haghparast
Summary: Psychostimulant Use Disorder is a chronic relapsing disorder with high motivation for drug abuse and is associated with various physical and mental health issues. There is currently no FDA-approved medication for treating psychostimulant abuse, making it crucial to understand the cellular and molecular changes involved in the disorder for developing effective medications.
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
(2023)
Article
Neurosciences
Judit Catala-Solsona, Pablo J. Lituma, Stefano Lutzu, Dolores Siedlecki-Wullich, Cristina Fabregas-Ordonez, Alfredo J. Minano-Molina, Carlos A. Saura, Pablo E. Castillo, Jose Rodriguez-Alvarez
Summary: Transcription factors called Nr4a have been found to play a crucial role in synaptic plasticity and cognitive function. In this study, it was discovered that neuronal activity enhances the expression and function of Nr4a2 in mouse hippocampal neurons through a pathway involving ionotropic glutamate receptors and other cellular factors. This activation of Nr4a2 promotes the production of a nerve growth factor called BDNF, which affects synaptic plasticity in the hippocampus. These findings suggest that targeting Nr4a2 could be a potential therapeutic approach for brain disorders associated with abnormal synaptic plasticity.
JOURNAL OF NEUROSCIENCE
(2023)
Article
Neurosciences
Maria Italia, Elena Ferrari, Monica Di Luca, Fabrizio Gardoni
Summary: AMPARs play a crucial role in excitatory synaptic transmission in the mammalian brain, with the GluA3 subunit being widely expressed and functionally relevant. Modulation of GluA3 through pharmacological means may offer a new approach for addressing altered glutamatergic synapses associated with neurodegenerative and neurodevelopmental disorders.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Neurosciences
Camille Quilgars, Jean-Rene Cazalets, Sandrine S. Bertrand
Summary: The study investigated the impact of metabotropic glutamate receptor (mGluR) activation on activity-dependent synaptic plasticity (ADSP) and the intrinsic membrane properties of lumbar motoneurons (MNs). Results showed subtype-specific and developmentally regulated modulation of ADSP and synaptic transmission at VLF-MN synapses, and a downregulation of mGluR gene expression with age in the ventral part of the lumbar spinal cord. Additionally, mGluR agonists induced distinct effects on motor burst amplitudes and locomotor rhythms, depending on the developmental stage of the animals.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Review
Neurosciences
D. Fernandez-Fernandez, J. A. Lamas
Summary: Potassium channels play a crucial role in neuronal excitability by regulating the resting membrane potential and influencing both long-term potentiation and short-term plasticity. Metabotropic receptors link neurotransmitter actions to modulation of potassium channels, impacting synaptic plasticity induction and maintenance.
Review
Cell Biology
Huiqin Zhang, Xuefan Jiang, Lina Ma, Wei Wei, Zehui Li, Surui Chang, Jiayu Wen, Jiahui Sun, Hao Li
Summary: Synaptic dysfunction is closely related to Alzheimer's disease (AD), mainly due to the disruption caused by beta-amyloid (Aβ). Aβ disrupts glutamate receptors and mediates synaptic toxicity through multiple mechanisms. Synaptic dysfunction plays a critical role in cognitive impairment of AD.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Shi-Xiao Peng, Yue-Ying Wang, Min Zhang, Yan-Yu Zang, Dan Wu, Jingwen Pei, Yansong Li, Jiapei Dai, Xiaoyun Guo, Xingguang Luo, Ning Zhang, Jian-Jun Yang, Chen Zhang, Xiang Gao, Na Liu, Yun Stone Shi
Summary: TARP gamma-8 expression level is associated with antisocial personality disorder (ASPD), and rs10420324G in CACNG8 is more susceptible to ASPD. Decreased TARP gamma-8 expression in mice leads to behavioral abnormalities similar to ASPD patients, partially explaining the neuronal basis for ASPD.
SCIENTIFIC REPORTS
(2021)
Review
Psychiatry
Katarzyna Anna Dudek, Fernanda Neutzling Kaufmann, Olivier Lavoie, Caroline Menard
Summary: Recent findings suggest that epigenetic modifications of genes involved in stress response are linked to resilience. For example, increased DNA methylation of the nonneuronal growth factor Gdnf in specific brain regions promotes stress resilience. However, more research is needed to establish sex specific differences and to identify novel epigenetic mechanisms that hold great promises for the field of psychiatry.
CURRENT OPINION IN PSYCHIATRY
(2021)
Editorial Material
Clinical Neurology
Caroline Menard, Tabrez J. Siddiqui, Derya Sargin, Ashley Lawson, Yves De Koninck, Judy Illes
CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES
(2022)
Review
Neurosciences
Ellen Doney, Alice Cadoret, Laurence Dion-Albert, Manon Lebel, Caroline Menard
Summary: Regulation of emotions involves not only the brain but also peripheral systems, and the prevalence of stress and mood disorders is on the rise in modern societies. Many individuals have poor responses to current treatments, underscoring the need for further research into emotion-related biology for innovative therapies. Studies on inflammation-related mechanisms in mood regulation and stress responses using animal models highlight potential translational value and novel therapeutic approaches.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Aki Takahashi, Hossein Aleyasin, Mihaela A. Stavarache, Long Li, Flurin Cathomas, Lyonna F. Parise, Hsiao-Yun Lin, C. Joseph Burnett, Antonio Aubry, Meghan E. Flanigan, Anna Brancato, Caroline Menard, Madeline L. Pfau, Veronika Kana, Jun Wang, Georgia E. Hodes, Tetsuya Sasaki, Michael G. Kaplitt, Sonoko Ogawa, Bruce S. McEwen, Scott J. Russo
Summary: The study demonstrated the significant role of IL-1 beta in regulating aggression, showing that non-aggressive mice had higher levels of IL-1 beta in the DRN compared to aggressive mice, and pharmacological antagonism or gene knockdown of IL-1 receptors in the DRN increased aggressive behavior. This suggests that modulation of 5-HT neuronal activity by IL-1 beta signaling in the DRN controls the expression of aggressive behavior.
MOLECULAR PSYCHIATRY
(2022)
Editorial Material
Clinical Neurology
Melissa L. Perreault, Malcolm King, Chelsea Gabel, Christopher J. Mushquash, Yves De Koninck, Ashley Lawson, Caterina Marra, Caroline Menard, Jennie Z. Young, Judy Illes
CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES
(2023)
Review
Endocrinology & Metabolism
Laurence Dion-Albert, Luisa Bandeira Binder, Beatrice Daigle, Amandine Hong-Minh, Manon Lebel, Caroline Menard
Summary: The prevalence of mental disorders is increasing rapidly, with major sex differences observed. This article provides an overview of the immune, endocrine, vascular, and transcriptional changes associated with these disorders, and explores their potential impact on neurovascular integrity and pathogenesis. Understanding these adaptations is crucial not only for mental disorders, but also for cardiovascular diseases and stroke.
FRONTIERS IN NEUROENDOCRINOLOGY
(2022)
Article
Behavioral Sciences
Alice Cadoret, Laurence Dion-Albert, Sara Amrani, Laurianne Caron, Mathilde Theberge, Audrey Turmel, Manon Lebel, Caroline Menard
Summary: Experiences and emotions have an impact on memory consolidation and brain neuronal circuits. This study investigates the relationship between emotional valence, memory encoding, and blood-brain barrier (BBB) gene expression. The results show correlations between learning difficulties, anxiety, stress, and changes in BBB-associated gene expression.
BEHAVIOURAL BRAIN RESEARCH
(2023)
Review
Neurosciences
Sam E. J. Paton, Jose L. Solano, Francois Coulombe-Rozon, Manon Lebel, Caroline Menard
Summary: The environment has a significant influence on mental states and behaviors, with biological barriers such as the blood-brain barrier and gut barrier serving as important channels for environmental information. Changes in the structural, social, and motor environment at different stages of life can affect the function and integrity of these barriers, leading to behavioral consequences. Each environmental component is associated with distinct immune profiles, glucocorticoid responses, and gut microbiome compositions, which have unique effects on the barriers. The interactions between barriers and the environment are sensitive to changes throughout life, and positive or negative alterations during critical developmental stages can have long-lasting cognitive and behavioral consequences. Understanding these pathways of environmental influence is important in understanding mental disorders and identifying potential pharmacological targets for protection and treatment. This review summarizes the mechanisms through which environmental factors such as social interactions, structural complexity, and physical exercise influence barrier composition, morphology, and development, and discusses the outcomes and implications of these interactions in psychiatric disorders.
JOURNAL OF PSYCHIATRY & NEUROSCIENCE
(2023)
Review
Neurosciences
Laurence Dion-Albert, Katarzyna A. Dudek, Scott J. Russo, Matthew Campbell, Caroline Menard
Summary: The neurovascular unit (NVU) plays a crucial role in maintaining homeostasis in the central nervous system (CNS) by facilitating substance exchange between the blood and the brain. Recent studies have shown that the NVU also affects brain function, cognition, and emotional processes, especially under stress. Understanding the mechanisms of NVU regulation can provide valuable insights for research on cognition, stress, and brain disorders.
TRENDS IN NEUROSCIENCES
(2023)
Editorial Material
Immunology
Jose L. Solano, Caroline Menard
Summary: Psychological stress exacerbates gut inflammation and dysmotility by modifying enteric glia and neurons.
Meeting Abstract
Neurosciences
Ellen Doney, Laurence Dion-Albert, Francois Coulombe-Rozon, Natasha Osbourne, Renaud Bernatchez, Sam Paton, Fernanda Neutzling Kaufmann, Roseline Olory Agomma, Jose Luis Solano Lopez, Raphael Gaumond, Katarzyna Dudek, Joanna Kasia Szyszkowicz, Manon Lebel, Alain Doyen, Audrey Durand, Flavie Lavoie-Cardinal, Marie-Claude Audet, Caroline Menard
NEUROPSYCHOPHARMACOLOGY
(2022)
Meeting Abstract
Neurosciences
Laurence Dion-Albert, Alice Cadoret, Ellen Doney, Fernanda Neutzling Kaufmann, Katarzyna A. Dudek, Beatrice Daigle, Lyonna F. Parise, Flurin Cathomas, Nalia Samba, Natalie Hudson, Manon Lebel, Matthew Campbell, Gustavo Turecki, Naguib Mechawar, Caroline Menard
JOURNAL OF PSYCHIATRY & NEUROSCIENCE
(2022)
Meeting Abstract
Neurosciences
Laurence Dion-Albert, Alice Cadoret, Ellen Doney, Fernanda Neutzling Kaufmann, Katarzyna Anna Dudek, Beatrice Daigle, Lyonna Parise, Flurin Cathomas, Nalia Samba, Natalie Hudson, Manon Lebel, Signature Consortium, Matthew Campbell, Gustavo Turecki, Naguib Mechawar, Caroline Menard
BIOLOGICAL PSYCHIATRY
(2022)
Meeting Abstract
Neurosciences
Benedetta Bigio, Danielle Zelli, Paolo de Angelis, Caroline Menard, Georgia Hodes, Catherine Pena, Aleksander Mathe, Michael J. Meaney, Eric Nestler, Scott Russo, Carla Nasca
NEUROPSYCHOPHARMACOLOGY
(2021)
Meeting Abstract
Neurosciences
Caroline Menard
NEUROPSYCHOPHARMACOLOGY
(2021)