Article
Neurosciences
Arena Manning, Victor Han, Alexa Stephens, Rose Wang, Nicholas Bush, Michelle Bard, Jan M. Ramirez, Franck Kalume
Summary: Mutations in the NDUFS4 gene can lead to Leigh syndrome (LS), the most common form of mitochondrial disease in children. Epileptic seizures, which are difficult to treat and indicate poor prognosis, are a significant clinical feature of LS. By studying the effects of Ndufs4 gene mutations in GABAergic interneurons of mice, we gain insights into the epilepsy phenotype of LS and the cellular mechanisms underlying epilepsy in LS and other mitochondrial diseases.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Clinical Neurology
Nina E. Ottosson, Malin Silvera Ejneby, Xiongyu Wu, Argel Estrada-Mondragon, Michelle Nilsson, Urban Karlsson, Melanie Schupp, Salome Rognant, Thomas Andrew Jepps, Peter Konradsson, Fredrik Elinder
Summary: Resin acid derivatives have been found to activate the hK(V)7.2/7.3 channel, showing potential for epilepsy treatment and demonstrating significant antiseizure effects in animal studies. These compounds act on the channel in a unique way compared to existing drugs, and have fewer side effects.
Article
Multidisciplinary Sciences
Yuan-Hung Lin King, Chao Chen, John V. Lin King, Jeffrey Simms, Edward Glasscock, Shi-Bing Yang, Yuh-Nung Jan, Lily Y. Jan
Summary: Adult hippocampal neurogenesis plays a critical role in learning and memory, and the K(v)1.1 channel has been identified as an important regulator in this process. Deletion of K(v)1.1 leads to overproliferation and depletion of adult neural stem cells, impairs maturation and integration of new cells in the hippocampus, and moderately affects hippocampus-dependent contextual fear learning and memory.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Xi Liu, Zhi Qiao, Yuming Chai, Zhi Zhu, Kaijie Wu, Wenliang Ji, Daguang Li, Yujie Xiao, Lanqun Mao, Chao Chang, Quan Wen, Bo Song, Yousheng Shu
Summary: Midinfrared stimulation (MIRS) is a potential neuromodulation approach that exerts nonthermal, long-distance, and reversible modulatory effects on ion channel activity, neuronal signaling, and sensorimotor behavior. This method provides gain control over spiking activities and modulates startle responses, making it suitable for clinical application.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Pharmacology & Pharmacy
Ernesto Griego, Melissa Hernandez-Frausto, Luis A. Marquez, Leonardo Lara-Valderrabano, Carolina Lopez Rubalcava, Emilio J. Galvan
Summary: The study identifies electrophysiologic alterations in animals treated with MK-801, including up-regulation of ionic currents and reduced excitability, which may contribute to cognitive symptoms of schizophrenia. Additionally, the study demonstrates reduced cognitive performance in animals treated with MK-801.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Neurosciences
Hannah Scheiblich, Joern R. Steinert
Summary: Regulation of neuronal activity through nitric oxide (NO) involves suppression of potassium and sodium channel activities, leading to decreased excitability. NO mediates these effects via redox signaling on ion channels, with an additional cGMP-mediated component specifically for sodium currents. The study provides new insights into nitrergic activities in modulating neuronal function following nNOS activation.
Article
Biochemistry & Molecular Biology
Bokyung Song, Sung-Joong Lee, Chong-Hyun Kim
Summary: In a ATP-induced cortical injury model, ATP and cytokine TNF-alpha significantly affect the physiological activities of neurons and microglia at day 3 post-injection, while IL-10 and IL-4 effectively suppress these changes in both cell types.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Fumeng Zheng, Haruyuki Kamiya
Summary: Modification of axonal excitability affects information transfer in the brain, but the functional significance of this modulation remains unclear. This study focused on the activity-dependent broadening of action potentials in the hippocampal mossy fibers and found that it is dependent on the inactivation of axonal K+ channels. Computer simulations showed that removing the inactivation process abolished the use-dependent broadening of action potentials. This highlights the critical role of K+ channel inactivation in regulating axonal excitability and short-term plasticity at this synapse.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Article
Biology
Emmet M. Power, Dharshini Ganeshan, Karl J. Iremonger
Summary: The effect of estradiol replacement therapy on CRH neuron excitability is complex, as it increases two types of potassium channel currents but does not change overall spiking excitability.
JOURNAL OF EXPERIMENTAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Bank G. Fenyves, Andreas Arnold, Vaibhav G. Gharat, Carmen Haab, Kiril Tishinov, Fabian Peter, Dominique de Quervain, Andreas Papassotiropoulos, Attila Stetak
Summary: This study reveals that the MiRP family member mps-2 controls long-term associative memory in AVA neurons and plays a key role in age-related memory decline. The research demonstrates that mps-2 modulates LTAM through the regulation of K(v)2.1/KVS-3 and K(v)2.2/KVS-4 heteromeric potassium channels, contributing to a programmed control of physiological age-dependent memory decline.
Article
Medicine, General & Internal
Hao-Wen Teng, Jowy Tani, Tsui-San Chang, Hung-Ju Chen, Yi-Chen Lin, Cindy Shin-Yi Lin, Jia-Ying Sung
Summary: The study revealed increased sensory axonal excitability in fibromyalgia patients compared to healthy controls, with a negative correlation between increased subexcitability and fibromyalgia impact questionnaire score. Computer modeling suggested the altered excitability pattern was due to dysfunction of paranodal fast K+ channels.
JOURNAL OF THE FORMOSAN MEDICAL ASSOCIATION
(2021)
Article
Neurosciences
Jing Wu, Lynda El-Hassar, Dibyadeep Datta, Merrilee Thomas, Yalan Zhang, David P. Jenkins, Nicholas J. Deluca, Manavi Chatterjee, Valentin K. Gribkoff, Amy F. T. Arnsten, Leonard K. Kaczmarek
Summary: The ability of monkeys and rats to perform spatial working memory tasks is dependent on the interaction between hyperpolarization-activated cyclic nucleotide-gated (HCN) channels and Slack sodium-activated potassium (KNa) channels in the prefrontal cortex. Activation of HCN channels leads to suppression of neuronal excitability, thus affecting working memory performance.
MOLECULAR NEUROBIOLOGY
(2023)
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)
Article
Multidisciplinary Sciences
Mara C. P. Rue, Leandro M. Alonso, Eve Marder
Summary: The study investigated the effects of altered extracellular potassium concentration on the output of the pyloric circuit in the crab, revealing changes in neuronal activity and circuit robustness in response to high potassium saline and subsequent challenges.
Review
Biochemistry & Molecular Biology
Cole Malloy, Maisie Ahern, Lin Lin, Dax A. Hoffman
Summary: The coordinated action of voltage-gated ion channels, often associated with auxiliary subunits, is crucial for controlling neuronal physiology and circuit function in the brain. Dipeptidyl aminopeptidase-like protein 6 (DPP6), an auxiliary subunit expressed in multiple brain regions, interacts with A-type K+ channels to regulate their distribution and gating properties, as well as plays an independent role in synaptic formation and maintenance. Dysfunction of DPP6 is associated with various neurological disorders. Understanding the contribution of DPP6 to these disorders is an active area of research.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Min-Yu Sun, Mariangela Chisari, Lawrence N. Eisenman, Charles F. Zorumski, Steven J. Mennerick
JOURNAL OF NEUROPHYSIOLOGY
(2017)
Article
Neurosciences
Courtney Sobieski, Michael J. Fitzpatrick, Steven J. Mennerick
JOURNAL OF NEUROSCIENCE
(2017)
Article
Immunology
Geraldine J. Kress, Fan Liao, Julie Dimitry, Michelle R. Cedeno, Garret A. FitzGerald, David M. Holtzman, Erik S. Musiek
JOURNAL OF EXPERIMENTAL MEDICINE
(2018)
Article
Multidisciplinary Sciences
Courtney Sobieski, Natasha Warikoo, Hong-Jin Shu, Steven Mennerick
Article
Multidisciplinary Sciences
Min-Yu Sun, Amanda Taylor, Charles F. Zorumski, Steven Mennerick
Article
Neurosciences
Mariangela Chisari, Timothy J. Wilding, Samuel Brunwasser, Kathiresan Krishnan, Mingxing Qian, Ann Benz, James E. Huettner, Charles F. Zorumski, Douglas F. Covey, Steven Mennerick
Article
Biology
Luis Carrillo-Reid, Michelle Day, Zhong Xie, Alexandria E. Melendez, Jyothisri Kondapalli, Joshua L. Plotkin, David L. Wokosin, Yu Chen, Geraldine J. Kress, Michael Kaplitt, Ema Ilijic, Jaime N. Guzman, S. Savio Chan, D. James Surmeier
Review
Endocrinology & Metabolism
Peter M. Lambert, Xinguo Lu, Charles F. Zorumski, Steven Mennerick
Summary: The rise of ketamine and brexanolone as rapid antidepressant treatments has prompted research into their common mechanisms. These drugs have distinct characteristics compared to traditional antidepressants in terms of onset time and duration of effect. Based on existing studies, network disinhibition and increased high-frequency oscillations are potential mechanisms underlying the acute effects of rapid antidepressants.
JOURNAL OF NEUROENDOCRINOLOGY
(2022)
Article
Neurosciences
Yukitoshi Izumi, Anil G. Cashikar, Kathiresan Krishnan, Steven M. Paul, Douglas F. Covey, Steven J. Mennerick, Charles F. Zorumski
Summary: Inflammatory cells synthesize and release the oxysterol 25-hydroxycholesterol (25HC), which has antiviral and immunomodulatory properties. Activation of innate immunity by lipopolysaccharide (LPS) affects 25HC production in microglia and influences CA1 hippocampal synaptic plasticity and learning. 25HC serves as a key modulator of synaptic plasticity and memory under proinflammatory stimuli.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Neurosciences
Peter M. Lambert, Richard Ni, Ann Benz, Nicholas R. Rensing, Michael Wong, Charles F. Zorumski, Steven Mennerick
Summary: This study explored the EEG signatures of neurosteroid allopregnanolone and other GABA(A) positive modulators in mice, as well as their similarities and differences with ketamine. The results suggest that rapid antidepressants with different molecular substrates may remain separated at the level of large-scale ensemble activity, but could have commonalities in more discrete circuits and/or in the context of a dysfunctional brain.
NEUROPSYCHOPHARMACOLOGY
(2023)
Article
Psychiatry
Yukitoshi Izumi, Angela M. Reiersen, Eric J. Lenze, Steven J. Mennerick, Charles F. Zorumski
Summary: By studying rat hippocampal slices, it was found that fluvoxamine and other selective serotonin reuptake inhibitors (SSRIs) can overcome the inhibition of long-term potentiation (LTP) caused by acute inflammatory stimulus, possibly through activation of Sigma 1 receptors (S1Rs) and synthesis of neurosteroids. These SSRIs may be beneficial in diseases involving inflammatory stress.
TRANSLATIONAL PSYCHIATRY
(2023)
Article
Neurosciences
Xinguo Lu, Peter Lambert, Ann Benz, Charles F. Zorumski, Steven J. Mennerick
Summary: AlloP is a neurosteroid that enhances GABAA receptor inhibition and is used to treat postpartum depression. Its antidepressant mechanism involves selective action at GABAA receptors containing the d subunit. However, recent research suggests that hippocampal PV interneurons have low sensitivity to AlloP and are unlikely to contribute to the mood-altering effects of neurosteroids through GABA effects.
Review
Neurosciences
Jamie L. Maguire, Steven Mennerick
Summary: Neuroactive steroids are a new class of antidepressants that have a rapid and long-lasting effect, different from previous treatments and other compounds. They act by positive allosteric modulation of GABA(A) receptors, and may also target intracellular pathways. Further research is needed to understand their molecular mechanisms and effects on behavior.
NEUROPSYCHOPHARMACOLOGY
(2023)
Article
Neurosciences
Charles F. Zorumski, Steven M. Paul, Douglas F. Covey, Steven Mennerick
NEUROBIOLOGY OF STRESS
(2019)
Article
Pharmacology & Pharmacy
Sampurna Chakrabarti, Mingxing Qian, Kathiresan Krishnan, Douglas F. Covey, Steven Mennerick, Gustav Akk
MOLECULAR PHARMACOLOGY
(2016)