Review
Neurosciences
Paola Plazas, Ana Belen Elgoyhen
Summary: Vertebrate hair cell systems are modulated by efferent fibers, with mammalian studies limited and zebrafish emerging as a preferred research model. The zebrafish lateral line efferent system resembles that of mammals, providing valuable insights into various aspects of hair cell biology.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Geriatrics & Gerontology
Lauren A. Poppi, Mark J. Bigland, Ethan T. Cresswell, Hessam Tabatabaee, David Lorincz, Hannah R. Drury, Robert J. Callister, Joseph C. Holt, Rebecca Lim, Alan M. Brichta, Doug W. Smith
Summary: Cholinergic signaling in the peripheral vestibular sensory organs is vulnerable to aging processes, leading to molecular and functional age-related changes. This was evidenced by reduced expression of nicotinic receptor subunit genes and reduced conductance through alpha9/10 subunit-containing nicotinic receptors in older mice. Given the importance of these organs to balance maintenance and visual gaze stability, further investigation into altered peripheral vestibular function in older humans is warranted.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Natalia Roa-Vidal, Adriana Rodriguez-Aponte, Jose Lasalde-Dominicci, Coral Capo-Velez, Manuel Delgado-Velez
Summary: Macrophages play a vital role in defending the body and exhibit remarkable adaptability in response to invading pathogens and stimuli. The activation of the cholinergic anti-inflammatory pathway, especially mediated by the alpha 7-nAChR, is crucial in suppressing proinflammatory cytokines and maintaining homeostasis. This review focuses on macrophage polarization, the influence of viral infections on macrophage inflammatory phenotypes, and the emerging significance of dup alpha 7 in macrophage polarization and inflammation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Physiology
Joseph F. Margiotta, Kristen M. Smith-Edwards, Andrea Nestor-Kalinoski, Brian M. Davis, Kathryn M. Albers, Marthe J. Howard
Summary: The study demonstrates that interneuronal communication in the intestine is primarily mediated by nAChRs and/or 5-HT(3)Rs, with cholinergic MG neurons displaying spontaneous Ca2+ transients and fast responses to stimulation, associated with synaptic inputs.
FRONTIERS IN PHYSIOLOGY
(2021)
Review
Neurosciences
Marcela Lipovsek, Irina Marcovich, Ana Belen Elgoyhen
Summary: Nicotinic acetylcholine receptors (nAChRs) are a subfamily of ion channels with five subunits, found in most animal clades. They are divided into three subgroups based on tissue of expression: neuronal, muscle, and hair cells, with different subunits including the recently identified alpha 9 and alpha 10 subunits. The alpha 9 alpha 10 nAChRs show the most divergence among nicotinic receptors, with differences in sequence conservation, expression pattern, subunit co-assembly rules, and functional properties.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Review
Chemistry, Medicinal
Edouard Montigne, David Balayssac
Summary: This scoping review provides an overview of studies on peripheral neuropathic pain (PNP) in rodent models, exploring compounds targeting cholinergic neurotransmission. The results highlight the potential of cholinergic compounds for the management of neuropathic pain, emphasizing the need for clinical trials.
Article
Neurosciences
Agustin E. Carpaneto Freixas, Marcelo J. Moglie, Tais Castagnola, Lucia Salatino, Sabina Domene, Irina Marcovich, Sofia Gallino, Carolina Wedemeyer, Juan D. Goutman, Paola V. Plazas, Ana Belen Elgoyhen
Summary: The lateral line (LL) is a sensory system that allows fish and amphibians to detect water currents. Our research shows that the alpha 9 subunits are enriched in zebrafish HCs, playing a key role in ACh-mediated effects in the LL.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Audiology & Speech-Language Pathology
E. Gabriel Romero, O. Laurence Trussell
Summary: This review examines central nervous system aspects of the cochlear efferent system, including the physiological properties of the neurons, their synaptic inputs, modulation, and the effects of efferent axon collaterals within the brainstem.
Editorial Material
Biochemistry & Molecular Biology
Lili Anglister, Israel Silman, Hermona Soreq
Summary: This special issue covers a wide range of topics and disciplines presented at the XVIth International Symposium on Cholinergic Mechanisms. The authors discuss recent developments in the field, including the association of cholinergic transmission with important neurological and neuromuscular diseases in the central and peripheral nervous systems.
JOURNAL OF NEUROCHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Lisa Klotz, Ralf Enz
Summary: The study analyzed the expression and localization of mGluR7a and mGluR7b in mouse cochlear wholemounts, finding a presynaptic localization of mGluR7a at inner hair cells (IHCs) and co-localization of mGluR7b with mGluR7a at IHC ribbon synapses. The numbers of mGluR7a and mGluR7b puncta were reduced at higher frequencies and in older animals, indicating potential age and frequency-related changes in the cochlea.
Review
Biochemistry & Molecular Biology
Toshio Takahashi
Summary: Stem cells have extensive proliferative potential and can differentiate into mature cell types, with their self-renewal mechanisms providing insight into multicellular organism development. Cholinergic signaling plays a pivotal role in controlling stem cell behavior, with recent studies focusing on understanding stem cell regulation at cellular and molecular levels.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Alessandro Giraudo, Marco Pallavicini, Cristiano Bolchi
Summary: The alpha 9- and alpha 7-containing nicotinic acetylcholine receptors play key roles in physiological and pathological processes. Selective ligands for these receptors are important research tools and potential therapeutic agents. While there is a wealth of information on alpha 7-nAChR ligands, the understanding of selective alpha 9-nAChR ligands is limited. This review provides a comprehensive overview of the latter, along with recent updates on alpha 7-nAChR ligands.
PHARMACOLOGICAL RESEARCH
(2023)
Article
Neurosciences
Yugandhar Ramakrishna, Marco Manca, Elisabeth Glowatzki, Soroush G. Sadeghi
Summary: Vestibular nerve afferents can be categorized into regular and irregular groups based on the variability of interspike intervals in their resting discharge. Most afferents receive inputs from different types of hair cells, with calyx terminals containing KCNQ potassium channels and muscarinic acetylcholine receptors and being regulated by cholinergic efferent inputs.
Article
Neurosciences
Shivang Sullere, Alissa Kunczt, Daniel S. McGehee
Summary: Chronic pain is a burden for individuals and society, but opioids have limitations. Activation of cholinergic mechanisms can relieve pain without tolerance, reward, or withdrawal symptoms.
Article
Biochemistry & Molecular Biology
Daniela Anni, Eva-Maria Weiss, Debarpan Guhathakurta, Yagiz Enes Akdas, Julia Klueva, Stefanie Zeitler, Maria Andres-Alonso, Tobias Huth, Anna Fejtova
Summary: The study shows that Aβ 1-42 and Aβ 1-16 can increase the size of the recycling pool of synaptic vesicles, driven by enhanced endogenous cholinergic signaling.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Multidisciplinary Sciences
Pankhuri Vyas, Jingjing Sherry Wu, Adrian Jimenez, Elisabeth Glowatzki, Paul Albert Fuchs
SCIENTIFIC REPORTS
(2019)
Article
Multidisciplinary Sciences
Jiwon Ryu, Philippe F. Y. Vincent, Nikolaos K. Ziogas, Leyan Xu, Shirin Sadeghpour, John Curtin, Athanasios S. Alexandris, Nicholas Stewart, Richard Sima, Sascha du Lac, Elisabeth Glowatzki, Vassilis E. Koliatsos
Article
Multidisciplinary Sciences
Marco Manca, Elisabeth Glowatzki, Dale C. Roberts, Gene Y. Fridman, Felix P. Aplin
SCIENTIFIC REPORTS
(2019)
Article
Biology
Jingjing Sherry Wu, Eunyoung Yi, Marco Manca, Hamad Javaid, Amanda M. Lauer, Elisabeth Glowatzki
Review
Clinical Neurology
Hiroshi Nakanishi, Pragya Prakash, Taku Ito, H. Jeffrey Kim, Carmen C. Brewer, Danielle Harrow, Isabelle Roux, Seiji Hosokawa, Andrew J. Griffith
FRONTIERS IN NEUROLOGY
(2020)
Article
Neurosciences
Zhou Yu, J. Michael McIntosh, Soroush G. Sadeghi, Elisabeth Glowatzki
JOURNAL OF NEUROPHYSIOLOGY
(2020)
Article
Neurosciences
Y. Zhang, E. Glowatzki, I. Roux, P. A. Fuchs
JOURNAL OF NEUROPHYSIOLOGY
(2020)
Article
Neurosciences
Eric D. Young, Jingjing Sherry Wu, Mamiko Niwa, Elisabeth Glowatzki
Summary: The study analyzed the nature of multiphasic waveforms recorded in rat afferent dendrites. It found that the charge of EPSCs is similar for multiphasic and monophasic EPSCs, with EPSC amplitudes decreasing with the number of release events. The results did not provide evidence of mini-EPSCs, and suggested that most findings can be explained by either uniquantal or multiquantal release models.
JOURNAL OF NEUROPHYSIOLOGY
(2021)
Article
Neurosciences
Mamiko Niwa, Eric D. Young, Elisabeth Glowatzki, Anthony J. Ricci
Summary: The study revealed that pillar synapses mature later than modiolar synapses in the hair cell-spiral ganglion neuron synapse, with a significant difference in release process which may partly drive afferent firing properties.
JOURNAL OF NEUROPHYSIOLOGY
(2021)
Article
Multidisciplinary Sciences
Keiji Honda, Hyun Jae Lee, Andrew J. Griffith, Isabelle Roux
Summary: Research on mutant mouse models of human hearing and balance disorders has unveiled changes in the development and function of neurosensory epithelia, but limited knowledge exists about the endolymphatic sac. Difficulty in visualizing and microdissecting this tissue, largely due to its single-cell layer composition, hinders further understanding of this understudied part of the inner ear.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2021)
Article
Biochemistry & Molecular Biology
Adebolajo Adeyemo, Rabia Faridi, Parna Chattaraj, Rizwan Yousaf, Risa Tona, Samuel Okorie, Thashi Bharadwaj, Liz M. Nouel-Saied, Anushree Acharya, Isabelle Schrauwen, Robert J. Morell, Suzanne M. Leal, Thomas B. Friedman, Andrew J. Griffith, Isabelle Roux
Summary: Although variant alleles of hundreds of genes are associated with sensorineural deafness in children, the genes and alleles involved remain largely unknown in the Sub-Saharan regions of Africa. In a study of families in or near Ibadan, Nigeria, a high level of genetic heterogeneity of hearing loss was discovered, with likely causal variants identified in genes reported to underlie deafness in other populations. The results suggest challenges for molecular genetic screening, counseling, and early intervention in this population.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)
Article
Medicine, Research & Experimental
Kevin Isgrig, Yasuko Ishibashi, Hyun Jae Lee, Jianliang Zhu, Mhamed Grati, Jean Bennett, Andrew J. Griffith, Isabelle Roux, Wade W. Chien
Summary: Inner ear gene therapy using AAVs has been successfully applied in mouse models, improving auditory function. This study identifies AAV8BP2 and AAV8 as highly efficient vectors for transducing cells in the cochlear lateral wall and the endolymphatic sac.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2022)
Article
Genetics & Heredity
Isabelle Roux, Cristina Fenollar-Ferrer, Hyun Jae Lee, Parna Chattaraj, Ivan A. Lopez, Kyungreem Han, Keiji Honda, Carmen C. Brewer, John A. Butman, Robert J. Morell, Donna M. Martin, Andrew J. Griffith
Summary: Enlargement of the endolymphatic sac, duct, and vestibular aqueduct (EVA) is a common inner ear malformation in patients with hearing loss, and is associated with pathogenic variants in SLC26A4. However, in European-Caucasian populations, around 50% of EVA patients have no pathogenic alleles of SLC26A4. This study found that CHD7 variants can cause EVA and nonsyndromic hearing loss, and suggest that CHD7 should be included in DNA sequence analyses for EVA patients.
Article
Multidisciplinary Sciences
Caroline Siebald, Philippe F. Y. Vincent, Riley T. Bottom, Shuohao Sun, Daniel O. J. Reijntjes, Marco Manca, Elisabeth Glowatzki, Ulrich Muller
Summary: This study reveals three molecularly defined subtypes of type I SGNs using single-cell RNA sequencing technology, but the extent to which they correspond to physiological subtypes is unclear. Using genetically marked SGN subtypes, the researchers found that Lypd1-CreERT2 expressing SGNs have a low SR and preferentially innervate the IHC modiolar side, while Calb2-CreERT2 expressing SGNs have a wider range of SRs and preferentially innervate the IHC pillar side.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)