Review
Biochemistry & Molecular Biology
Maria Italia, Elena Ferrari, Monica Diluca, Fabrizio Gardoni
Summary: A prominent feature of neurodegenerative diseases is synaptic dysfunction and spine loss. Misfolded proteins, such as tau and alpha-synuclein, play a critical role in driving synaptic toxicity at excitatory glutamatergic synapses. Understanding the role of these proteins in impairing the function of glutamate receptors can provide insights into the pathology of neurodegenerative diseases.
Article
Multidisciplinary Sciences
Xiumin Chen, Yuko Fukata, Masaki Fukata, Roger A. Nicoll
Summary: This study reveals the essential role of the MAGUK family of synaptic scaffolding proteins in LTP, with PSD-95 requiring binding to ADAM22 for synaptic transmission enhancement. Additionally, an alternative pathway involving SAP102 is proposed, independent of ADAM22.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Martin Hruska, Rachel E. Cain, Matthew B. Dalva
Summary: This study reveals the impact of nanoscale organization of glutamate receptors on synaptic features, with receptors containing specific subunits forming specific subsynaptic regions, which is crucial for events such as cell death and synaptic plasticity.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Qixu Cai, Menglong Zeng, Xiandeng Wu, Haowei Wu, Yumeng Zhan, Ruijun Tian, Mingjie Zhang
Summary: CaMKIIα plays a crucial role in synapses by interacting with Shank3 and GluN2B, regulating synaptic plasticity through the modulation of Ca2+ concentration and phosphatases. The shuttling of CaMKIIα between specific PSD subcompartments and PSD condensates controlled by protein phosphatases contributes to PSD assembly enlargement and structural long-term potentiation.
Article
Neurosciences
William J. Wright, Yan Dong
Summary: Glutamatergic synapses play a crucial role in encoding cocaine memories, with the generation of silent synapses during cocaine experience contributing to the consolidation of these memories. These silent synapses alternate between AMPAR-absent and AMPAR-containing states after cue-induced retrieval of cocaine memories, reflecting the dynamic process of memory destabilization and reconsolidation in response to cocaine-associated cues.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Cell Biology
Tiziana Ravasenga, Massimo Ruben, Vincenzo Regio, Alice Polenghi, Enrica Maria Petrini, Andrea Barberis
Summary: The induction of long-term potentiation at an individual glutamatergic spine leads to depression of nearby GABAergic inhibitory synapses, while more distant synapses are potentiated, requiring the involvement of L-type calcium channels and calpain.
Article
Behavioral Sciences
Yasmin Cruz Del Angel, James E. Orfila, Paco S. Herson, Amy Brooks-Kayal, Marco I. Gonzalez
Summary: Epilepsy is a brain disorder characterized by recurrent seizures and can lead to behavioral disorders and altered cognition. Changes in AMPAR signaling induced by seizures may impact synaptic plasticity, thus affecting learning and memory functions in individuals with epilepsy.
EPILEPSY & BEHAVIOR
(2021)
Article
Multidisciplinary Sciences
Benjamin Compans, Come Camus, Emmanouela Kallergi, Silvia Sposini, Magalie Martineau, Corey Butler, Adel Kechkar, Remco Klaassen, Natacha Retailleau, Terrence J. Sejnowski, August B. Smit, Jean-Baptiste Sibarita, Thomas M. Bartol, David Perrais, Vassiliki Nikoletopoulou, Daniel Choquet, Eric Hosy
Summary: Long-term depression (LTD) of synaptic strength is associated with circuit remodeling, memory encoding, and erasure. P2XR- and NMDAR-dependent LTD are linked to distinct molecular modifications that lead to specific changes in synapse function.
NATURE COMMUNICATIONS
(2021)
Article
Biology
Maximilian F. Eggl, Thomas E. Chater, Janko Petkovic, Yukiko Goda, Tatjana Tchumatchenko
Summary: This study reveals how seemingly spontaneous synaptic fluctuations and local plasticity both contribute to population-level synaptic dynamics.
COMMUNICATIONS BIOLOGY
(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
Biology
Jesus Perez-Ortega, Tzitzitlini Alejandre-Garcia, Rafael Yuste
Summary: Neuronal ensembles, identified as coactive groups of neurons in cortical activity, can last for weeks in the visual cortex of awake mice, with some ensembles maintaining activity for up to 46 days and displaying stronger functional connectivity.
Article
Multidisciplinary Sciences
Dimitra Vardalaki, Kwanghun Chung, Mark T. Harnett
Summary: Newly generated excitatory synapses in the mammalian cortex lack sufficient AMPA-type glutamate receptors to mediate neurotransmission, resulting in functionally silent synapses that require activity-dependent plasticity to mature. However, adults retain a capacity for neural plasticity and flexible learning, suggesting that the formation of new connections is still prevalent. The study found that a significant percentage of synapses lacked AMPA receptors and were located on thin dendritic protrusions. These silent synapses can be activated through a process called Hebbian plasticity.
Article
Neurosciences
Randa Kassab
Summary: This article introduces a new method for modeling the CA3 network, focusing on the impact of long-term potentiation (LTP) on CA3 functional connectivity. The study found that only a small fraction of active synapses should be connected to activated cells to achieve optimal performance. This control of connectivity is achieved by acetylcholine modulating the trafficking and adjustment of the AMPA receptors.
Article
Biochemistry & Molecular Biology
Tatyana Y. Postnikova, Sergey L. Malkin, Maria Zakharova, Ilya Smolensky, Olga E. Zubareva, Aleksey Zaitsev
Summary: Disruption of glutamate clearance in the synaptic cleft can lead to synaptic dysfunction and neurological diseases, potentially causing excitotoxicity. Increased glutamate clearance has been shown to reduce long-term synaptic potentiation (LTP). Treatment with the enhancer of glutamate transporter 1 expression, ceftriaxone, weakened LTP in the hippocampus of young rats, likely due to reduced spillover of glutamate leading to decreased activation of synapses.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Emmanouela Kallergi, Akrivi-Dimitra Daskalaki, Angeliki Kolaxi, Come Camus, Evangelia Ioannou, Valentina Mercaldo, Per Haberkant, Frank Stein, Kyriaki Sidiropoulou, Yannis Dalezios, Mikhail M. Savitski, Claudia Bagni, Daniel Choquet, Eric Hosy, Vassiliki Nikoletopoulou
Summary: Autophagy is required for pruning dendritic spines and long-term depression (LTD), a major form of synaptic plasticity. LTD induces the biogenesis of autophagic vesicles in dendrites to facilitate the degradation of postsynaptic proteins. Autophagy plays a crucial role in dendritic spine pruning and synaptic plasticity.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Anna Di Maio, Arianna De Rosa, Silvia Pelucchi, Martina Garofalo, Benedetta Marciano, Tommaso Nuzzo, Fabrizio Gardoni, Andrea M. Isidori, Monica Di Luca, Francesco Errico, Andrea De Bartolomeis, Elena Marcello, Alessandro Usiello
Summary: This study examined mRNA and protein expression of key spine shaping proteins in the brains of schizophrenia patients and found altered expression of CAP2 and DLG1 genes in different brain regions, suggesting their potential involvement in synaptic dysfunction associated with psychiatric disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Christian Litke, Anna M. Hagenston, Ann-Kristin Kenkel, Eszter Paldy, Jianning Lu, Rohini Kuner, Daniela Mauceri
Summary: This study reveals the role of histone deacetylase 4 (HDAC4) in sensitization of spinal cord neurons and its regulation of the organic anion transporter OAT1. Noxious stimuli cause HDAC4 to be exported from the nucleus and inactivated, while a mutant form of HDAC4 remains in the nucleus. The regulation of OAT1 by HDAC4 is shown to be involved in the development of inflammatory hypersensitivity. This research highlights HDAC4 as an important epigenetic regulator and suggests OAT1 as a potential target for pain-relieving therapies.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Marlene Spitzel, Elise Wagner, Maximilian Breyer, Dorothea Henniger, Mehtap Bayin, Lukas Hofmann, Daniela Mauceri, Claudia Sommer, Nurcan Ueceyler
Summary: Fabry disease is a rare disorder caused by the deficiency of the GLA enzyme, leading to Gb3 accumulation in the neurons of FD patients. This study investigated the relationship between Gb3 accumulation and FD pain using a GLA knockout mouse model. The results showed a higher Gb3 load in the DRG of GLA KO mice and a suppressed immune response in the DRG of old GLA KO mice. Dysregulation of immune-related genes may be linked to lower gene expression levels of pain-associated ion channels. Additionally, impaired FLOT1 distribution patterns and aberrant behavior were observed in GLA KO mice.
Editorial Material
Neurosciences
Daniela Mauceri, Rohini Kuner
Summary: This study identifies the sodium-calcium exchanger 3 as a negative regulator of temporal summation and hypersensitivity in the spinal cord, linking it to pathological pain through its modulation of calcium homeostasis.
Review
Biochemistry & Molecular Biology
Maria Italia, Elena Ferrari, Monica Diluca, Fabrizio Gardoni
Summary: A prominent feature of neurodegenerative diseases is synaptic dysfunction and spine loss. Misfolded proteins, such as tau and alpha-synuclein, play a critical role in driving synaptic toxicity at excitatory glutamatergic synapses. Understanding the role of these proteins in impairing the function of glutamate receptors can provide insights into the pathology of neurodegenerative diseases.
Article
Cell Biology
Gianluca Figlia, Sandra Mueller, Anna M. Hagenston, Susanne Kleber, Mykola Roiuk, Jan-Philipp Quast, Nora ten Bosch, Damian Carvajal Ibanez, Daniela Mauceri, Ana Martin-Villalba, Aurelio A. Teleman
Summary: The research shows that different Rag GTPase genes and isoforms can differentially regulate mTORC1 activity and modulate the responsiveness of mammalian cells to amino acid availability. This sheds light on the important role of the mechanistic target of rapamycin complex 1 (mTORC1) in regulating cellular anabolism and catabolism.
NATURE CELL BIOLOGY
(2022)
Article
Neurosciences
Elisabetta Gerace, Lorenzo Polenzani, Maurizio Magnani, Elisa Zianni, Gabriella Stocca, Fabrizio Gardoni, Domenico E. Pellegrini-Giampietro, Renato Corradetti
Summary: The chronic treatment with trazodone or paroxetine increases the expression of GluA2 AMPA receptor subunits in the hippocampus of rats, but does not lead to enhanced basal neurotransmission or the appearance of functional calcium-permeable AMPARs.
Article
Pharmacology & Pharmacy
Elena Ferrari, Diego Scheggia, Elisa Zianni, Maria Italia, Marta Brumana, Luca Palazzolo, Chiara Parravicini, Andrea Pilotto, Alessandro Padovani, Elena Marcello, Ivano Eberini, Paolo Calabresi, Monica Diluca, Fabrizio Gardoni
Summary: Toxic aggregates of alpha-synuclein play a key role in Parkinson's disease by inducing synaptic dysfunction and loss. This study identifies Rabphilin-3A as a novel target to counteract alpha syn-induced synaptic loss and suggests that restoring the synaptic functions of Rabphilin-3A could slow down the progression of Parkinson's disease.
PHARMACOLOGICAL RESEARCH
(2022)
Review
Cell Biology
Daniela Mauceri
Summary: Pain is an unpleasant sensation resulting from tissue damage, and when it persists after the injury has resolved, it becomes pathological. The transition from acute to chronic pain involves plasticity events along the neural pathways and alterations in gene expression. Epigenetic mechanisms play a crucial role in these adaptive processes in the nervous system.
Review
Pharmacology & Pharmacy
Alerie G. de la Fuente, Silvia Pelucchi, Jerome Mertens, Monica Di Luca, Daniela Mauceri, Elena Marcello
Summary: Ageing is the main risk factor for most primary neurodegenerative disorders, and protein misfolding and toxic protein accumulation are considered causative events. However, other biological pathways affected by brain ageing also contribute to pathogenesis. This article discusses the involvement of mechanisms controlling neuronal structure, gene expression, autophagy, cell metabolism, and neuroinflammation in the onset and progression of neurodegenerative disorders, and reviews therapeutic strategies aiming to normalize these pathways for increased brain resilience.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Editorial Material
Cell Biology
Manuela Simonetti, Daniela Mauceri
Article
Multidisciplinary Sciences
Gioia Marino, Federica Campanelli, Giuseppina Natale, Maria De Carluccio, Federica Servillo, Elena Ferrari, Fabrizio Gardoni, Maria Emiliana Caristo, Barbara Picconi, Antonella Cardinale, Vittorio Loffredo, Francesco Crupi, Elvira De Leonibus, Maria Teresa Viscomi, Veronica Ghiglieri, Paolo Calabresi
Summary: Intensive physical activity improves motor functions and cognitive deficits in early-stage Parkinson's disease (PD) patients. This study investigated the mechanisms behind these beneficial effects by conducting an intensive treadmill training program on rats with alpha-synuclein (a-syn) preformed fibrils. The training resulted in improved motor control, visuospatial learning, and plasticity in the brain, which were associated with the modulation of specific receptors. These findings suggest that intensive exercise can rescue early neuroplastic alterations caused by a-syn aggregates and reduce their spread to vulnerable brain areas.
