Review
Neurosciences
Jane Yang, Steven A. Prescott
Summary: Neurons maintain homeostasis by adjusting ion channel expression levels through negative feedback. Degeneracy and pleiotropy play important roles in homeostatic regulation, where degeneracy enables compensatory changes in multiple channels and pleiotropy complicates regulation by affecting multiple properties. Understanding feedback loops and their interactions provides insight into the failure modes of homeostatic regulation, which can aid in developing more effective treatments for chronic neurological disorders.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Article
Immunology
Nolan M. Dvorak, Nadia D. Domingo, Cynthia M. Tapia, Paul A. Wadsworth, Mate Marosi, Yosef Avchalumov, Chanida Fongsaran, Leandra Koff, Jessica Di Re, Catherine M. Sampson, Timothy J. Baumgartner, Pingyuan Wang, Paula P. Villarreal, Olivia D. Solomon, Sonja J. Stutz, Aditi, Jacob Porter, Komi Gbedande, Brendan Prideaux, Thomas A. Green, Erin H. Seeley, Parimal Samir, Kelley T. Dineley, Gracie Vargas, Jia Zhou, Irma Cisneros, Robin Stephens, Fernanda Laezza
Summary: The study investigates the impact of TNF on neuronal excitability in hyperinflammatory cerebral malaria (eCM) and identifies the signaling network involving TNFR1, JAK2, FGF14, and Nav1.6. Plasmodium chabaudi infection increases Nav1.6 channel conductance in CA1 pyramidal neurons through the TNFR1-JAK2-FGF14-Nav1.6 pathway, leading to hyperexcitability. Targeting FGF14 may serve as a potential therapeutic strategy for mitigating TNF-mediated neuroinflammation.
JOURNAL OF NEUROINFLAMMATION
(2023)
Article
Biology
Vladimir A. Martinez-Rojas, Francesca Pischedda, Isabel Romero-Maldonado, Bouchra Khalaf, Giovanni Piccoli, Paolo Macchi, Carlo Musio
Summary: Nucleoporins (NUPs) are proteins that make up the nuclear pore complexes (NPCs) and play a significant role in the pathophysiology of neurodegenerative diseases (NDDs). This study found that downregulation of Nup358 can modify cell-membrane excitability and contribute to neuronal activity regulation.
Article
Clinical Neurology
Lauren E. Bleakley, Chaseley E. McKenzie, Ming S. Soh, Ian C. Forster, Paulo Pinares-Garcia, Alicia Sedo, Anirudh Kathirvel, Leonid Churilov, Nikola Jancovski, Snezana Maljevic, Samuel F. Berkovic, Ingrid E. Scheffer, Steven Petrou, Bina Santoro, Christopher A. Reid
Summary: Pathogenic variants in HCN1 are linked to developmental and epileptic encephalopathies, with the Hcn1(M294L) mouse model reproducing phenotypic features seen in patients with the HCN1 M305L variant. This mouse model provides insight into the pathological mechanisms underlying hyperexcitability in HCN1 developmental and epileptic encephalopathy.
Review
Biochemistry & Molecular Biology
Jereme G. Spiers, Joern R. Steinert
Summary: Nitric oxide signaling in the brain exerts its effects on ion channels through various pathways, leading to functional regulation under physiological conditions or dysfunction in diseases. The complexity of this regulation presents challenges in understanding the role of NO signaling in physiology and pathology.
Article
Multidisciplinary Sciences
Grant P. Higerd-Rusli, Sidharth Tyagi, Christopher A. Baker, Shujun Liu, Fadia B. Dib-Hajj, Sulayman D. Dib-Hajj, Stephen G. Waxman
Summary: Inflammation causes pain by altering the ionic currents in nociceptors, resulting in increased excitability. NaV1.7 and KV7.2 channels play opposing roles in nociceptor excitability. This study used live-cell imaging to investigate the mechanisms by which inflammatory mediators regulate the abundance of these channels at axonal surfaces. The results revealed a cell biological mechanism for inflammatory pain and suggested NaV1.7 trafficking as a potential therapeutic target.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biology
Irina Ignatova, Roman Frolov, Soile Nymark
Summary: Recent studies have found voltage-activated Na+ channels in the retinal pigment epithelium (RPE), which are important for the phagocytosis of photoreceptor outer segments and maintaining retinal homeostasis.
Article
Cell Biology
Zhongming Ma, Usha Paudel, J. Kevin Foskett
Summary: The intensity of taste is strongly influenced by temperature, but there is a lack of comprehensive understanding about the physiological, hedonic, and commercial implications of this relationship. This study used patch-clamp electrophysiology to investigate the effects of temperature on taste-bud cell electrical excitability, revealing that temperature significantly affects the electrical activity of type II taste-bud cells. These findings provide a mechanism for understanding how temperature influences taste sensitivity and perception.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2023)
Review
Cell Biology
Paola Alberti, Sara Semperboni, Guido Cavaletti, Arianna Scuteri
Summary: Neurons are permanent cells that rely on finely tuned homeostasis for proper function, with microtubules playing a key role in cellular equilibrium by mobilizing molecular cargos. Alterations in cytoskeletal dynamics can impact neuronal excitability, highlighting the importance of understanding these processes in human diseases and neuronal functioning. Microscopic approaches for visualizing and assessing the cytoskeleton, particularly in mitochondrial trafficking, are essential for further research in this area.
Review
Biochemistry & Molecular Biology
Dmitry Lim, Laura Tapella, Giulia Dematteis, Maria Talmon, Armando A. Genazzani
Summary: This article reviews the role of Ca2+ and CaN signaling in astroglial pathophysiology, focusing on the emerging physiological role of CaN in astrocytes. The authors propose a model for the context-dependent switch of CaN activity from the post-transcriptional regulation of cell proteostasis in healthy astrocytes to the CaN-dependent transcriptional activation in neuroinflammation-associated diseases.
NEUROCHEMICAL RESEARCH
(2023)
Article
Multidisciplinary Sciences
Murat Kirtay, Josefine Sell, Christian Marx, Holger Haselmann, Mihai Ceanga, Zhong-Wei Zhou, Vahid Rahmati, Joanna Kirkpatrick, Katrin Buder, Paulius Grigaravicius, Alessandro Ori, Christian Geis, Zhao-Qi Wang
Summary: ATR, a key regulator of DNA damage response and replication stress, also plays a role in regulating neuronal activity beyond its known functions. Deletion of ATR in neurons leads to increased intrinsic activity, aberrant firing, and heightened epileptiform activity, potentially increasing susceptibility to ataxia and epilepsy.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Yi Lu, Hong Wang, Junqing Yang, Wengao Jiang, Hong Xin, Ying Luo, Santiago Loya-Lopez, Huaiyu Gu, Dongzhi Ran
Summary: This study investigated the effects of MEHP on the central nervous system by assessing the electrophysiological properties of rat CA3 hippocampal neurons. The results showed that MEHP decreased the amplitude of spontaneous action potential and the frequency of mini-excitatory postsynaptic currents. It also inhibited the activity of ion channels, suggesting its distinct role in neural transmission.
Article
Neurosciences
Changning Xie, Fangyun Liu, Hailan He, Fang He, Leilei Mao, Xiaole Wang, Fei Yin, Jing Peng
Summary: This study investigates the role of HCN1 channel variants in epilepsy and their effects on neuronal properties. The researchers identified five new cases with different HCN1 variants, including both pathogenic and likely pathogenic variants. They found that these variants impaired the biophysical properties of HCN1 channels and affected protein expression in neurons. Additionally, the variants influenced neuronal excitability and firing rates. These findings expand our understanding of HCN1-related epilepsy and provide insights into potential personalized therapies for patients.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Pharmacology & Pharmacy
Martin Kruse, Rayne J. Whitten
Summary: Phosphoinositides, despite being a minor component of cell lipids, play essential roles in regulating neuronal activities. Activation of neurotransmitter receptors can rapidly deplete phosphoinositide levels, significantly impacting neuronal behavior. A comprehensive model has been developed to study the connection between muscarinic acetylcholine signaling, phosphoinositide metabolism, and action potential firing in sympathetic neurons.
FRONTIERS IN PHARMACOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Carlos Ancaten-Gonzalez, Ignacio Segura, Rosangelina Alvarado-Sanchez, Andres E. Chavez, Ramon Latorre
Summary: BK channels are large conductance potassium channels that play crucial roles in regulating neuronal excitability and synaptic communication in the brain. Their dysfunction has been implicated in various neurological disorders. Here, we discuss the physiological importance of BK channels and their contribution to the pathophysiology of different neurological disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Christina Gross, Xiaodi Yao, Tobias Engel, Durgesh Tiwari, Lei Xing, Shane Rowley, Scott W. Danielson, Kristen T. Thomas, Eva M. Jimenez-Mateos, Lindsay M. Schroeder, Raymund Y. K. Pun, Steve C. Danzer, David C. Henshall, Gary J. Bassell
Article
Immunology
Yijun Pan, Jennifer L. Short, Stephanie A. Newman, Kwok H. C. Choy, Durgesh Tiwari, Christopher Yap, Danielle Senyschyn, William A. Banks, Joseph A. Nicolazzo
BRAIN BEHAVIOR AND IMMUNITY
(2018)
Article
Neurosciences
Christina Gross, Anwesha Banerjee, Durgesh Tiwari, Francesco Longo, Angela R. White, A. G. Allen, Lindsay M. Schroeder-Carter, Joseph C. Krzeski, Nada A. Elsayed, Rosemary Puckett, Eric Klann, Ralph A. Rivero, Shannon L. Gourley, Gary J. Bassell
NEUROPSYCHOPHARMACOLOGY
(2019)
Article
Neurosciences
Durgesh Tiwari, Darrin H. Brager, Jeffrey K. Rymer, Alexander T. Bunk, Angela R. White, Nada A. Elsayed, Joseph C. Krzeski, Andrew Snider, Lindsay M. Schroeder Carter, Steve C. Danzer, Christina Gross
NEUROBIOLOGY OF DISEASE
(2019)
Article
Multidisciplinary Sciences
Kevin X. Zhang, Shane D'Souza, Brian A. Upton, Stace Kernodle, Shruti Vemaraju, Gowri Nayak, Kevin D. Gaitonde, Amanda L. Holt, Courtney D. Linne, April N. Smith, Nathan T. Petts, Matthew Batie, Rajib Mukherjee, Durgesh Tiwari, Ethan D. Buhr, Russell N. Van Gelder, Christina Gross, Alison Sweeney, Joan Sanchez-Gurmaches, Randy J. Seeley, Richard A. Lang
Article
Cell Biology
Ranjithmenon Muraleedharan, Mruniya Gawali, Durgesh Tiwari, Abitha Sukumaran, Nicole Oatman, Jane Anderson, Diana Nardini, Mohammad Alfrad Nobel Bhuiyan, Ivan Tkac, Amber Lynne Ward, Mondira Kundu, Ronald Waclaw, Lionel M. Chow, Christina Gross, Raghavendra Rao, Stefanie Schirmeier, Biplab Dasgupta
Article
Neurosciences
Durgesh Tiwari, Tori L. Schaefer, Lindsay M. Schroeder-Carter, Joseph C. Krzeski, Alexander T. Bunk, Emma V. Parkins, Andrew Snider, Reese Danzer, Michael T. Williams, Charles V. Vorhees, Steve C. Danzer, Christina Gross
EXPERIMENTAL NEUROLOGY
(2020)
Review
Neurosciences
Candi L. LaSarge, Raymund Y. K. Pun, Zhiqing Gu, Matthew R. Riccetti, Devi V. Namboodiri, Durgesh Tiwari, Christina Gross, Steve C. Danzer
Summary: Mutations in genes regulating mTOR pathway signaling are recognized as a significant cause of epilepsy, often caused by somatic mutations affecting variable numbers of neurons. Deleting Pten from hippocampal granule cells can lead to seizures of varying severity, demonstrating that knockout cell load is a critical variable regulating disease phenotype.
PROGRESS IN NEUROBIOLOGY
(2021)
Article
Psychiatry
Tori L. Schaefer, Amy A. Ashworth, Durgesh Tiwari, Madison P. Tomasek, Emma V. Parkins, Angela R. White, Andrew Snider, Matthew H. Davenport, Lindsay M. Grainger, Robert A. Becker, Chandler K. Robinson, Rishav Mukherjee, Michael T. Williams, Jay R. Gibson, Kimberly M. Huber, Christina Gross, Craig A. Erickson
Summary: Fragile X syndrome is the most common cause of inherited intellectual disability, resulting from the loss of Fragile X Protein. While modulation of the GABAergic system has been suggested as a treatment strategy, clinical trials using broad spectrum GABA receptor-specific agonists have not shown broad improvements in FXS phenotypes. The experimental drug BAER-101, a selective GABA(A) alpha 2/alpha 3 agonist, has shown promising results in reducing hyperexcitability in cortical circuits and improving certain phenotypes in Fmr1 KO mice.
FRONTIERS IN PSYCHIATRY
(2021)
Correction
Neurosciences
Christina Gross, Anwesha Banerjee, Durgesh Tiwari, Francesco Longo, Angela R. White, A. G. Allen, Lindsay M. Schroeder-Carter, Joseph C. Krzeski, Nada A. Elsayed, Rosemary Puckett, Eric Klann, Ralph A. Rivero, Shannon L. Gourley, Gary J. Bassell
NEUROPSYCHOPHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Emma V. Parkins, John M. Burwinkel, Ruvi Ranatunga, Sarah Yaser, Yueh-Chiang Hu, Durgesh Tiwari, Christina Gross
Summary: Dendritic spines are essential for neuronal communication in the brain, and microRNA-324-5p plays a crucial role in their formation and regulation. This study demonstrates that miR-324-5p is developmentally regulated and its loss leads to changes in dendritic spine density and protein expression at different developmental time points. The findings highlight the importance of context in studying miRNA and its role in synaptic refinement.
JOURNAL OF MOLECULAR NEUROSCIENCE
(2023)
Article
Neurosciences
Durgesh Tiwari, Valerine Rajathi, Jeffrey K. Rymer, Lindsay N. Beasley, Amanda M. McGann, Alexander T. Bunk, Emma V. Parkins, McKenzie F. Rice, Katie E. Smith, David M. Ritter, Angela R. White, Carolyn M. Doerning, Christina Gross
Summary: Approximately one-third of epilepsy patients suffer from treatment-resistant seizures, necessitating the development of alternative therapeutic strategies. miRNA-induced silencing has emerged as a potential novel treatment target for epilepsy, but its regulation in females and under the influence of female hormones remains understudied. In this study, we investigated the impact of hormonal fluctuations on miRNA-induced silencing in female mice and observed differential effects on the efficacy of antagomirs targeting miR-324-5p and its downstream target Kv4.2. Our findings suggest that hormonal fluctuations in sexually mature female mice can influence miRNA-induced silencing and potentially affect the effectiveness of miRNA-based treatments for epilepsy in females.
Article
Nanoscience & Nanotechnology
Durgesh Laxman Tiwari, K. Sivasankaran
INTERNATIONAL JOURNAL OF NANOSCIENCE
(2018)
Review
Anatomy & Morphology
Durgesh Tiwari, Katrina Peariso, Christina Gross
DEVELOPMENTAL DYNAMICS
(2018)