Article
Cardiac & Cardiovascular Systems
Moradeke A. Bamgboye, Maria K. Traficante, Josiah Owoyemi, Deborah DiSilvestre, Daiana C. O. Vieira, Ivy E. Dick
Summary: Mutations in the CaV1.2 L-type calcium channel can cause longQT type 8 (LQT8), leading to fatal cardiac arrhythmias. Current therapies with calcium channel blockers (CCBs) are unsuccessful due to mutation-induced deficits in channel inactivation, resulting in decreased use-dependent block of the mutant channel. Understanding the interplay between inactivation deficits and state-dependent block may guide the development of improved therapies for channelopathic mutations.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2022)
Article
Multidisciplinary Sciences
Ehsan Sedaghat-Nejad, Jay S. Pi, Paul Hage, Mohammad Amin Fakharian, Reza Shadmehr
Summary: The ability of the brain to control movement accurately relies on the cerebellum. Recent research has found that cerebellar P cells transmit information by synchronizing their spikes and utilizing disinhibition to convey important signals for movement control.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Neurosciences
Vanessa L. Hull, Yan Wang, Travis Burns, Sarah Sternbach, Shuaishuai Gong, Jennifer McDonough, Fuzheng Guo, Laura N. Borodinsky, David Pleasure
Summary: Canavan disease is a pediatric leukodystrophy caused by mutations in the ASPA gene, resulting in a deficiency of the enzyme aspartoacylase. This leads to increased levels of N-acetyl-L-aspartate (NAA) in the brain and various neurological symptoms. In a mouse model of Canavan disease, researchers found that Bergmann glia (BG) exhibited significant morphological alterations and dysfunction, which preceded cerebellar degeneration. However, treatment with an antisense oligonucleotide targeting Nat8l, which reduces NAA production, was able to repair the BG and improve motor function. This suggests that restoring BG integrity may be a potential therapeutic strategy for Canavan disease.
Article
Neurosciences
David D. Bushart, Annie J. Zalon, Hongjiu Zhang, Logan M. Morrison, Yuanfang Guan, Henry L. Paulson, Vikram G. Shakkottai, Hayley S. McLoughlin
Summary: SCA3 is the second most common CAG repeat disease caused by a glutamine-encoding expansion in the ATXN3 protein, leading to degeneration of the spinocerebellum and progressive motor coordination disorders. Studies suggest that early abnormalities in cerebellar cortical Purkinje neuron excitability may underlie SCA3, and intervention can restore neuronal excitability. While a broader range of potassium channel transcripts may be reduced in late-stage SCA3, cerebellar Purkinje neuron physiology remains stable despite worsening motor impairment, indicating dysfunction of other neuronal structures beyond the cerebellum may contribute to the progressive motor phenotype observed in SCA3.
Article
Biology
Michael A. Gaffield, Britton A. Sauerbrei, Jason M. Christie, Aya Ito-Ishida
Summary: The cerebellum plays a role in the initiation and timing of repeated motor actions, with Purkinje cell activity being modulated during task performance related to licking movements.
Article
Neurosciences
Liansheng Chang, Shahid Hussain Soomro, Hongfeng Zhang, Hui Fu
Summary: Ankfy1 protein plays a critical role in the development and maintenance of Purkinje cells in the cerebellum. Its absence leads to loss of most Purkinje cells in the cerebellum, resulting in impaired motor function.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Neurosciences
Alessandro Dorigo, Komali Valishetti, Florian Hetsch, Hideaki Matsui, Jochen C. Meier, Kazuhiko Namikawa, Reinhard W. Koester
Summary: The cerebellum exhibits functional regionalization in processing motor and sensory inputs. This study demonstrates that the establishment of specific functional domains in Purkinje cell (PC) layer during cerebellum development is driven by physiological activity of maturing PCs. Additionally, the formation of new dendritic spines parallels the time course of functional domain development.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2023)
Review
Biochemistry & Molecular Biology
Oscar Brenes, Michael Pusch, Fernando Morales
Summary: Myotonia congenita is a hereditary muscle disease caused by mutations in the CLCN1 gene, leading to abnormal function of the chloride ion channel and resulting in muscle hyperexcitability and other symptoms. This review examines over 350 reported mutations and analyzes their effects on the structure and function of the chloride ion channel.
Article
Pharmacology & Pharmacy
Shu-Tao Xie, Wen-Chu Fan, Xian-Sen Zhao, Xiao-Yang Ma, Ze-Lin Li, Yan-Ran Zhao, Fa Yang, Ying Shi, Hui Rong, Zhi-San Cui, Jun-Yi Chen, Hong-Zhao Li, Chao Yan, Qipeng Zhang, Jian-Jun Wang, Xiao-Yang Zhang, Xiao-Ping Gu, Zheng-Liang Ma, Jing-Ning Zhu
Summary: Specific medications for cerebellar ataxias are still lacking, but the activation of cerebellar microglia has been found to be common in ataxic patients and rodent models. This study provides direct evidence that activating cerebellar microglia induces ataxia symptoms and worsens motor deficits in a mouse model of cerebellar ataxia. The activation of microglia leads to the hyperexcitation of Purkinje cells which triggers ataxia, and inhibiting microglia activation can alleviate motor deficits in mice.
PHARMACOLOGICAL RESEARCH
(2023)
Article
Clinical Neurology
Catarina Osorio, Joshua J. White, Heiling Lu, Gerrit C. Beekhof, Francesca Romana Fiocchi, Charlotte A. Andriessen, Stephanie Dijkhuizen, Laura Post, Martijn Schonewille
Summary: Spinocerebellar ataxias are neurodegenerative diseases characterized by the development of ataxia due to cerebellar dysfunction. The main cells affected in these diseases are Purkinje cells, but the sequence of events leading to their dysfunction is poorly understood.
Article
Neurosciences
Yaiza M. Arenas, Vicente Felipo
Summary: Chronic hyperammonemia is a major cause of cognitive and motor impairment in hepatic encephalopathy patients. This study aimed to investigate the mechanism involving BDNF, TrkB, NF-kappa B, and various proteins in hyperammonemic rats. The results showed that increased BDNF levels enhanced TrkB activation, leading to PI3K-AKT-NF-kappa B pathway activation and increased content of glutaminase I, HMGB1, and TNF alpha. Blocking TrkB, PI3K, or components of the TNFR1-S1PR2-CCR2-BDNF-TrkB pathway reversed these changes. This TrkB-PI3K-AKT-NF-kappa B pathway activation may contribute to Purkinje neuron dysfunction and motor impairment in hyperammonemic rats and cirrhotic patients with hepatic encephalopathy.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Neurosciences
Wanchat Theeranaew, Hyo-Jung Kim, Kenneth Loparo, Ji-Soo Kim, Aasef G. Shaikh
Summary: The study found that hyperventilation has an instantaneous effect on the randomness of oscillatory waveforms, but has less substantial effects on oscillation intensity, and these deficits reverse immediately at the end of hyperventilation.
Editorial Material
Medicine, Research & Experimental
Dong Cheol Jang, Changhyeon Ryu, Geehoon Chung, Sun Kwang Kim, Sang Jeong Kim
Summary: Ca2+ transients can be observed in the distal dendrites of Purkinje cells (PCs) through specific firing patterns. The interspike interval threshold (ISIT) for Ca2+ transients in the distal dendrites of PC has been proposed. Activation of metabotropic glutamate receptor 1 (mGluR1) relieved the ISIT and allowed Ca2+ transients to occur with lower frequencies of spike firing, while blocking T-type Ca2+ channels or depleting the endoplasmic reticulum Ca2+ store increased the required frequency for Ca2+ transients. This strict ISIT in PCs may help reduce noise and improve information collection.
EXPERIMENTAL NEUROBIOLOGY
(2023)
Article
Neurosciences
Emilio R. Mustafa, Eder Gambeta, Robin N. Stringer, Ivana A. Souza, Gerald W. Zamponi, Norbert Weiss
Summary: This study suggests that rare variants in the gene CACNA1H may contribute to trigeminal neuralgia by altering the electrophysiological properties of ion channels, leading to enhanced neuronal excitability.
Article
Neurosciences
I-Shan Chen, Jodene Eldstrom, David Fedida, Yoshihiro Kubo
Summary: G-protein-gated inwardly rectifying K+ (GIRK; Kir3.x) channels play important roles in controlling cell excitation in various organs. Disease-associated mutations in these channels can lead to loss of K+ selectivity, with the G156S mutation showing a unique ion permeation pathway compared to other mutants.
JOURNAL OF PHYSIOLOGY-LONDON
(2022)
Article
Neurosciences
Catherine J. C. Weisz, Maria E. Rubio, Richard S. Givens, Karl Kandler
JOURNAL OF NEUROSCIENCE
(2016)
Article
Neurosciences
Catherine J. C. Weisz, Mohamed Lehar, Hakim Hiel, Elisabeth Glowatzki, Paul Albert Fuchs
JOURNAL OF NEUROSCIENCE
(2012)
Article
Neurosciences
Catherine J. C. Weisz, Elisabeth Glowatzki, Paul Albert Fuchs
JOURNAL OF NEUROSCIENCE
(2014)
Article
Multidisciplinary Sciences
Catherine Weisz, Elisabeth Glowatzki, Paul Fuchs
Article
Neurosciences
Robert S. Raike, Carolyn E. Pizoli, Catherine Weisz, Arn M. J. M. van den Maagdenberg, H. A. Jinnah, Ellen J. Hess
NEUROBIOLOGY OF DISEASE
(2013)
Article
Neurosciences
Lester Torres Cadenas, Matthew J. Fischl, Ctatherine J. C. Weisz
JOURNAL OF NEUROSCIENCE
(2020)
Editorial Material
Medicine, Research & Experimental
Sian R. Kitcher, Catherine J. C. Weisz
EMBO MOLECULAR MEDICINE
(2020)
Article
Neurosciences
Catherine J. C. Weisz, Sean-Paul G. Williams, Chad S. Eckard, Christopher B. Divito, David W. Ferreira, Kristen N. Fantetti, Shenin A. Dettwyler, Hou-Ming Cai, Maria E. Rubio, Karl Kandler, Rebecca P. Seal
Summary: The study reveals that cochlear outer hair cells, unlike inner hair cells, are capable of releasing glutamate and activating neurons in the cochlear nucleus at moderate sound levels.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Audiology & Speech-Language Pathology
Sian R. Kitcher, Alia M. Pederson, Catherine J. C. Weisz
Summary: This review article mainly introduces the release, action, and function of neurotransmitters in the mammalian cochlea, with an emphasis on the complexity of signaling.
Article
Neurosciences
Lester Torres Cadenas, Hui Cheng, Catherine J. C. Weisz
Summary: The descending auditory system modulates the ascending system, and the MOC neurons are involved in inhibiting the OHC-mediated cochlear amplification. The MNTB-MOC synapses exhibit enhanced short-term depression at higher calcium concentrations and at room temperature. High rates of MNTB activity cause a tonic synaptic depression of MNTB-MOC synapses. MNTB inhibition of MOC neurons persists despite tonic synaptic depression.
JOURNAL OF PHYSIOLOGY-LONDON
(2022)
Article
Biology
Michelle M. Frank, Austen A. Sitko, Kirupa Suthakar, Lester Torres Cadenas, Mackenzie Hunt, Mary Caroline Yuk, Catherine J. C. Weisz, Lisa Goodrich
Summary: We characterized murine brainstem olivocochlear neurons (OCNs) during postnatal development, in mature animals, and after sound exposure using single-nucleus sequencing, anatomical reconstructions, and electrophysiology. We identified markers for known medial (MOC) and lateral (LOC) OCN subtypes and found that they express distinct physiologically relevant genes that change over development. We also discovered a neuropeptide-enriched LOC subtype producing Neuropeptide Y along with other neurotransmitters. Acoustic trauma leads to strong upregulation of LOC neuropeptide expression, potentially providing sustained cochlear protection. OCNs have diffuse, dynamic effects on early auditory processing over timescales ranging from milliseconds to days.
Article
Neurosciences
Rodrigo Martinez-Monedero, Chang Liu, Catherine Weisz, Pankhuri Vyas, Paul Albert Fuchs, Elisabeth Glowatzki
Article
Veterinary Sciences
Rebecca L. Erickson, Matthew C. Terzi, Samer M. Jaber, F. Claire Hankenson, Andrew McKinstry-Wu, Max B. Kelz, James O. Marx
JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE
(2016)
Article
Neurosciences
Nihal A. Salem, Lawrence Manzano, Michael W. Keist, Olga Ponomareva, Amanda J. Roberts, Marisa Roberto, R. Dayne Mayfield
Summary: This study identified cell-type specific gene expression changes associated with alcohol dependence in the medial prefrontal cortex of mice. The results revealed dysregulated gene co-expression networks and differentially expressed genes in multiple cell types, highlighting the involvement of inhibitory neurons and astrocytes in alcohol dependence. Novel targets for studying molecular mechanisms contributing to alcohol dependence were also identified.
NEUROBIOLOGY OF DISEASE
(2024)
Article
Neurosciences
Laura E. Hawley, Megan Stringer, Abigail J. Deal, Andrew Folz, Charles R. Goodlett, Randall J. Roper
Summary: This study found that the overexpression of DYRK1A protein in Down syndrome mice varies with age, sex, and brain region, and reducing the copy number of Dyrk1a can decrease the expression of DYRK1A. These sex-specific patterns of DYRK1A overexpression may provide mechanistic targets for therapeutic intervention in Down syndrome.
NEUROBIOLOGY OF DISEASE
(2024)