Article
Biochemistry & Molecular Biology
Vincenza D'Angelo, Mauro Giorgi, Emanuela Paldino, Silvia Cardarelli, Francesca R. Fusco, Ilaria Saverioni, Roberto Sorge, Giuseppina Martella, Stefano Biagioni, Nicola B. Mercuri, Antonio Pisani, Giuseppe Sancesario
Summary: The study found regional differences in the expression and aggregation of A2A receptors in the basal ganglia of a DYT1 mouse model of dystonia, with varying levels of expression observed in different subpopulations of neurons. Based on the different expression patterns of A2A receptors among neuronal subpopulations, it suggests that the pathophysiology of dystonia may be associated with a functional imbalance between the indirect and direct pathways.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Clinical Neurology
Marlous C. M. van Der Weijden, Dayana Rodriguez-Contreras, Catherine C. S. Delnooz, Brooks G. Robinson, Alec F. Condon, Michelle L. Kielhold, Gilles N. Stormezand, Kai Yu Ma, Claudia Dufke, John T. Williams, Kim A. Neve, Marina A. J. Tijssen, Dineke S. Verbeek
Summary: This study described a unique dominantly inherited clinical phenotype in a 4-generation Dutch pedigree, identifying a novel DRD2 gene variant as likely causative. Functional characterization of the variant revealed altered D2 receptor activity in cell models and mouse brain slices, supporting its association with the hyperkinetic movement disorder in the pedigree.
MOVEMENT DISORDERS
(2021)
Review
Neurosciences
Frank S. Menniti, Thomas A. Chappie, Christopher J. Schmidt
Summary: PDE10A inhibitors, believed to selectively activate medium spiny neurons in the striatum, failed to show antipsychotic activity in patients with schizophrenia, in contrast to D2 antagonists. Understanding the similarities and differences between PDE10A inhibitors and D2 antagonists may provide insights into the mechanisms of antipsychotic drugs.
FRONTIERS IN NEUROSCIENCE
(2021)
Article
Multidisciplinary Sciences
Emil Warnberg, Arvind Kumar
Summary: This article discusses the role of midbrain dopaminergic neurons in the basal ganglia and how to explain how dopamine supports learning of continuous outputs instead of discrete action values. The authors propose a model and demonstrate its validity through a learning rule.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Taku Matsuda, Ryoma Morigaki, Yuki Matsumoto, Hideo Mure, Kazuhisa Miyake, Masahito Nakataki, Masafumi Harada, Yasushi Takagi
Summary: This study aimed to investigate the correlations between motor symptoms and obsessive-compulsive symptoms, as well as between the volumes of basal ganglia components and obsessive-compulsive symptoms. The results revealed a positive correlation between obsessive-compulsive symptoms and the volumes of the nucleus accumbens, while motor symptoms showed a negative correlation. This highlights the potential pathogenesis of obsessive-compulsive disorder and dystonia.
SCIENTIFIC REPORTS
(2022)
Article
Neurosciences
Lisa Rauschenberger, Esther-Marie Krenig, Alea Stengl, Susanne Knorr, Tristan H. Harder, Felix Steeg, Maximilian U. Friedrich, Kathrin Grundmann-Hauser, Jens Volkmann, Chi Wang Ip
Summary: The relationship between genotype and phenotype in DYT-TOR1A dystonia as well as the associated motor circuit alterations are still not fully understood. This study provides evidence that recovery from a peripheral nerve injury can trigger a dystonic phenotype in genetically predisposed mice. The analysis of neural structures and neurochemical abnormalities in the basal ganglia highlights the importance of extragenetic factors in the symptomatogenesis of DYT-TOR1A dystonia.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Cell Biology
Kristen Delevich, Benjamin Hoshal, Lexi Z. Zhou, Yuting Zhang, Satya Vedula, Wan Chen Lin, Juliana Chase, Anne G. E. Collins, Linda Wilbrecht
Summary: This study investigates the role of direct and indirect pathway spiny projection neurons (dSPNs and iSPNs) in choice rejection during learning. The results show that activation of iSPNs disrupts rejection of nonrewarded choices. These findings are important for designing interventions to enhance choice rejection in addiction or other conditions.
Article
Neurosciences
Alexandra B. Nelson, Allison E. Girasole, Hsien-Yang Lee, Louis J. Ptacek, Anatol C. Kreitzer
Summary: Abnormal involuntary movements, or dyskinesias, are observed in various neurologic disorders, and may be caused by alterations in neural activity or connectivity. This study shows that dysfunction in the indirect pathway of the striatum contributes to the development of dyskinesia in a mouse model, suggesting that hypoactivity in the indirect pathway may be a key mechanism for involuntary movements in other disorders.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Arnaud L. Lalive, Mauro Congiu, Christopher Lewis, Dominik Groos, Joseph A. Clerke, Anna Tchenio, Yuan Ge, Fritjof Helmchen, Manuel Mameli
Summary: Through experiments with mice, it was found that the activity of lateral habenula neurons decreases with the decrease of reward-related stimuli, and this phenomenon can guide reward-driven behavior through synaptic inhibition.
Article
Multidisciplinary Sciences
Matthew Baker, Seungwoo Kang, Sa-Ik Hong, Minryung Song, Minsu Abel Yang, Lee Peyton, Hesham Essa, Sang Wan Lee, Doo-Sup Choi
Summary: The authors found that GPe arky neurons are involved in reward-seeking behaviors and primarily project to the dorsolateral striatum. Genetic ablation of this circuit shift behavior from goal-directed to habitual seeking.
NATURE COMMUNICATIONS
(2023)
Review
Biochemistry & Molecular Biology
Juan Perez-Fernandez, Marta Barandela, Cecilia Jimenez-Lopez
Summary: Dopamine is a widely studied neurotransmitter due to its link to motor deficits in Parkinson's disease. Recent research in basal vertebrates, particularly lampreys, has provided insights into the evolution of the dopaminergic system, shedding light on the role of SNc/VTA neurons in modulating motor responses through the basal ganglia. The findings suggest that the key functions of the SNc/VTA dopaminergic neurons in controlling motor responses were already well-established in early vertebrate evolution.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Vinith Johnson, Robert Wilt, Roee Gilron, Juan Anso, Randy Perrone, Martijn Beudel, Dan Pina-Fuentes, Jeremy Saal, Jill L. Ostrem, Ian Bledsoe, Philip Starr, Simon Little
Summary: The study utilized a novel, sensing-enabled deep brain stimulator device implanted in a patient with cervical dystonia to record neural data and conduct a proof-of-principle trial. It found that low-frequency oscillations are related to dystonia and demonstrated the potential for a novel adaptive stimulation strategy.
EXPERIMENTAL NEUROLOGY
(2021)
Review
Neurosciences
Stefanie Perl, Anika Luettig, Rudiger Koehling, Angelika Richter
Summary: This review provides an overview of DBS research in animal models of dystonia, discussing the research aims, opportunities and limitations of different animal models, and technical challenges.
NEUROBIOLOGY OF DISEASE
(2022)
Article
Neurosciences
Eric N. Moca, Daniela Lecca, Keenan T. Hope, Fanny Etienne, Ari W. Schaler, Katherine Espinoza, Megan S. Chappell, Daniel T. Gray, David Tweedie, Shanaya Sidhu, Lindsay Masukawa, Hannah Sitoy, Rose Mathew, Daniel R. Saban, Nigel H. Greig, Lindsay M. De Biase
Summary: During aging, microglia display different properties and interactions with synapses, affecting nearby neurons. Our study reveals regional differences in microglial response to aging and highlights the importance of lysosome status in microglial aging.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Multidisciplinary Sciences
Sebastian Loens, Julius Verrel, Vera-Maria Herrmann, Amrei Kienzle, Elinor Tzvi, Anne Weissbach, Johanna Junker, Alexander Muenchau, Tobias Baeumer
Summary: The study found that motor sequence learning is impaired in cervical dystonia patients overall, and unlike healthy controls, patients did not show a learning effect in the first part of the experiment. However, visuomotor adaptation and eyeblink conditioning were normal in these patients.
SCIENTIFIC REPORTS
(2021)
Article
Neurosciences
Paola Bonsi, Antonella De Jaco, Laurent Fasano, Paolo Gubellini
Summary: This review provides an overview of the synaptic dysfunction caused by mutations in autism spectrum disorder (ASD)-linked genes affecting the postsynaptic neuronal compartment. The effects of ASD-associated genes can vary depending on developmental time and subcellular site of expression. Better modeling ASD in experimental animals is needed to improve understanding of these disorders and increase the translational value of preclinical studies.
NEUROBIOLOGY OF DISEASE
(2022)
Review
Biochemistry & Molecular Biology
Martina Montanari, Giuseppina Martella, Paola Bonsi, Maria Meringolo
Summary: Disturbances in the glutamatergic system have been observed in autism spectrum disorder (ASD). This review summarizes evidence from patient samples, postmortem studies, and animal models to explore the role of glutamate in the pathophysiology of ASD and its potential as a therapeutic target.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Clinical Neurology
Giulia Ponterio, Gaia Faustini, Ilham El Atiallah, Giuseppe Sciamanna, Maria Meringolo, Annalisa Tassone, Paola Imbriani, Silvia Cerri, Giuseppina Martella, Paola Bonsi, Arianna Bellucci, Antonio Pisani
Summary: This study reveals the relationship between TA and alpha-Syn and demonstrates that alterations in alpha-Syn and SNAREs characterize the synaptic dysfunction underlying DYT1 dystonia.
MOVEMENT DISORDERS
(2022)
Article
Psychiatry
Sara Schiavi, Emilia Carbone, Francesca Melancia, Alessandra di Masi, Marielle Jarjat, Frederic Brau, Silvia Cardarelli, Mauro Giorgi, Barbara Bardoni, Viviana Trezza
Summary: Pharmacological inhibition of PDE2A has been proposed as a novel therapeutic tool for Fragile X Syndrome (FXS) and Autism Spectrum Disorder (ASD). This study investigated the role of PDE2A in ASD pathogenesis using rat models, and found that PDE2A inhibition could improve social and cognitive impairments in these models.
TRANSLATIONAL PSYCHIATRY
(2022)
Review
Neurosciences
Alessandro Stefani, Mariangela Pierantozzi, Silvia Cardarelli, Lucrezia Stefani, Rocco Cerroni, Matteo Conti, Elena Garasto, Nicola B. Mercuri, Carmine Marini, Patrizia Sucapane
Summary: Magnetic Resonance-guided Focused Ultrasound (MRgFUS) is an effective micro-lesioning approach for pharmaco-resistant tremors, with potential applications in the treatment of Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis. It can also be used to temporarily open the blood-brain barrier, providing opportunities for drug delivery and cognitive improvement.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Peripheral Vascular Disease
Yang Chen, Seethalakshmi R. Iyer, Viacheslav O. Nikolaev, Fabio Naro, Manuela Pellegrini, Silvia Cardarelli, Xiao Ma, Hon-Chi Lee, John C. Burnett
Summary: This study demonstrated that pGC-A mediates aldosterone inhibition, MANP inhibits aldosterone via PDE2, and the inhibitory effect is mediated by a reduction of intracellular Ca2+ levels.
Article
Biochemistry & Molecular Biology
Silvia Cardarelli, Adriana Erica Miele, Federica Campolo, Mara Massimi, Patrizia Mancini, Stefano Biagioni, Fabio Naro, Mauro Giorgi, Michele Saliola
Summary: PDE5 is an enzyme that plays a crucial role in regulating cell signaling pathways. It has different assembly forms and subcellular localization, and its overexpression can disrupt metabolic balance and contribute to the development of certain diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Emanuela Paldino, Francesca Romana Fusco
Summary: Huntington's disease is a neurodegenerative disease caused by a mutation in the IT15 gene encoding huntingtin protein. Inflammation plays a significant role in neuronal death, making drugs targeting inflammation powerful tools for treating Huntington's disease.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Paola Imbriani, Giuseppina Martella, Paola Bonsi, Antonio Pisani
Summary: Parkinson's disease (PD) is a multifactorial disorder with genetic and environmental factors playing a part. Mitochondrial impairment and oxidative stress are important mechanisms in PD, supported by PD-associated genes involved in mitochondrial function. Dysfunction of mitochondria is closely linked to synaptic dysfunction, which is an early event before nigrostriatal neurodegeneration in PD.
NEUROBIOLOGY OF DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Mauro Giorgi, Adriana Erica Miele, Silvia Cardarelli, Alessandra Giorgi, Mara Massimi, Stefano Biagioni, Michele Saliola
Summary: Phosphodiesterases (PDEs) are a superfamily of enzymes that hydrolyze cyclic nucleotides (cAMP/cGMP) and play important roles in cell life. The cGMP-dependent PDE5 is the major enzyme in many mammalian tissues, regulating various cellular and tissue processes. Using Kluyveromyces lactis as a model organism, the roles of different isoforms (PDE5A1, A2, and A3) in cellular redox metabolism were studied, revealing their distinct functions. The study also identified the N-terminal peptide responsible for the assembly and mitochondrial localization of PDE5A1 and PDE5A2.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Clinical Neurology
Ada Ledonne, Mariangela Massaro Cenere, Emanuela Paldino, Vincenza D'Angelo, Sebastian Luca D'Addario, Nicolas Casadei, Annalisa Nobili, Nicola Berretta, Francesca R. Fusco, Rossella Ventura, Giuseppe Sancesario, Ezia Guatteo, Nicola Biagio Mercuri
Summary: Prolonged overexpression of alpha-synuclein has detrimental effects on the structural and functional properties of substantia nigra pars compacta dopamine neurons, including compromised soma and dendritic arborization, increased firing activity, and altered ion channel function.
MOVEMENT DISORDERS
(2023)
Review
Biochemistry & Molecular Biology
Annalisa Tassone, Maria Meringolo, Giulia Ponterio, Paola Bonsi, Tommaso Schirinzi, Giuseppina Martella
Summary: Strong evidence suggests that the decline in mitochondrial function is correlated with degenerative diseases. Various types of neurodegenerative diseases, such as Huntington's chorea and Parkinson's disease, share mitochondrial bioenergy dysregulation as a common feature. These diseases have different manifestations and genetic factors, but they both involve neuronal dysfunction and striatal impairment. This review focuses on describing the onset and development of both diseases in relation to mitochondrial dysfunction.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Medicine, General & Internal
Federica Gagliardi, Enke Baldini, Eleonora Lori, Silvia Cardarelli, Daniele Pironi, Augusto Lauro, Domenico Tripodi, Piergaspare Palumbo, Eleonora D'Armiento, Giuseppe Cavallaro, Andrea Polistena, Valerio D'Orazi, Simone Sibio, Poupak Fallahi, Alessandro Antonelli, Vito D'Andrea, Salvatore Ulisse, Salvatore Sorrenti
Summary: Benign and malignant thyroid diseases are linked to the occurrence of extrathyroidal malignancies, including colorectal cancers. Understanding the relationship between these diseases can provide insights into their etiology and/or progression, as well as potential shared genetic and environmental factors. Exploring the underlying molecular mechanisms can lead to improved clinical management and increased surveillance for patients with thyroid diseases at a higher risk of developing extrathyroidal malignancies.
JOURNAL OF CLINICAL MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Martina Montanari, Paola Imbriani, Paola Bonsi, Giuseppina Martella, Antonella Peppe
Summary: The enteric nervous system (ENS), composed of neurons and glial cells, regulates the motor and secretory functions of the gastrointestinal tract. Dysfunction of the connections between the brain and the GI tract is implicated in Parkinson's disease (PD). Alterations in the ENS, including α-synuclein aggregation, occur early in the disease and spread to the central nervous system. This review highlights the role of the ENS in PD pathogenesis and its potential as a target for new therapeutic approaches.
