Article
Neurosciences
Yoshihiro Egashira, Ayane Kumade, Akio Ojida, Fumihito Ono
Summary: This study addresses the importance of spontaneous synaptic transmission and reveals the differences in the quantity of SVs mobilized by high-frequency action potential firing and spontaneous recycling. It also highlights the activation of distinct molecular mechanisms during prolonged AP inhibition and the characteristics of the early-onset SV population.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Neurosciences
Maya G. Feldthouse, Nicholas P. Vyleta, Stephen M. Smith
Summary: This study investigates the role of phospholipase C (PLC) in mediating the relationship between extracellular calcium concentration and spontaneous glutamate release in neurons. The findings suggest that PLC may modulate spontaneous release by modifying the size of the readily releasable pool (RRP), but the specific role of PLC-beta 1 in this process remains unclear.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Beatriz Martinez-Rojas, Esther Giraldo, Ruben Grillo-Risco, Marta R. Hidalgo, Eric Lopez-Mocholi, Ana Alastrue-Agudo, Francisco Garcia-Garcia, Victoria Moreno-Manzano
Summary: This study demonstrates the transcriptional dysregulation in spinal cord injury and the impact of neural progenitor cell transplantation on gene expression. The dysregulated transcriptome in injured spinal cord tissue involves cAMP signalling genes, which are rescued by NPC transplantation. However, sustained inhibition of EPAC2 signalling pathway affects the therapeutic mechanisms of NPC-mediated treatment, leading to increased inflammation and hindered neuroplasticity.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Neurosciences
Marc A. Meadows, Veeramuthu Balakrishnan, Xiaohan Wang, Henrique von Gersdorff
Summary: The study demonstrates that elevating cAMP in AII-AC leads to a robust enhancement of glycine release through an EPAC2 and Ca2+ store signaling pathway. This finding contributes to a better understanding of how AII-AC crossover inhibitory circuits adapt to changes in ambient luminance.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Medicine, Research & Experimental
Viktor N. Tomilin, Kyrylo Pyrshev, Anna Stavniichuk, Naghmeh Hassanzadeh Khayyat, Guohui Ren, Oleg Zaika, Sherif Khedr, Alexander Staruschenko, Fang C. Mei, Xiaodong Cheng, Oleh Pochynyuk
Summary: Epac1 and Epac2 have similar but nonredundant roles in renal sodium handling. Inhibition of Epac signaling could be instrumental in the treatment of hypertensive states associated with ENaC overactivation.
Article
Biochemistry & Molecular Biology
Michel Rasmussen, Jiaming Zhou, Frank Schwede, Per Ekstrom
Summary: Retinitis pigmentosa (RP) leads to photoreceptor degeneration, and the interaction between cGMP and EPAC2 may play a role in this process. In RP mouse models, elevated cGMP levels and increased interactions with EPAC2 were observed in photoreceptors. Inhibition of EPAC2 activity may contribute to RP progression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Yuxiang Li, Fangchao Tong, Lu Liu, Zhongqian Su, Jing Ding, Qiang Wang, Xin Wang
Summary: Mossy fiber sprouting is a characteristic of epilepsy and plays a key role in neural circuit formation. CRMP2, whose phosphorylation state regulates neurite/axon outgrowth, has been reported to change in epilepsy patients and animal models. This study provides direct evidence supporting the role of CRMP2 in mossy fiber sprouting in an animal model of epilepsy.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Review
Neurosciences
Ryota Fukaya, Rinako Miyano, Himawari Hirai, Takeshi Sakaba
Summary: Presynaptic plasticity refers to the activity-dependent changes in neurotransmitter release, playing a crucial role in modulating synaptic strength. Among these changes, presynaptic potentiation mediated by cyclic adenosine monophosphate (cAMP) is widely observed and implicated in learning and memory. Researchers have used hippocampal mossy fiber-CA3 pyramidal cell synapses as a model to investigate presynaptic potentiation, as the mechanisms underlying it can be dissected through direct presynaptic recordings. Recent advancements in super-resolution microscopy and flash-and-freeze electron microscopy have provided insights into the nanoscale localization of release site molecules and synaptic vesicles during potentiation, shedding light on the molecular mechanisms involved. In light of these findings, this study aims to propose plausible mechanisms underlying cAMP-mediated presynaptic potentiation.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Chris S. Mesnard, Cody L. Barta, Asia L. Sladek, David Zenisek, Wallace B. Thoreson
Summary: The release of glutamate from rod and cone photoreceptor cells is facilitated by presynaptic ribbons composed mainly of the protein RIBEYE. The absence of ribbons in these cells leads to reduced temporal resolution, contrast sensitivity, and b-waves. The readily releasable pool of vesicles and the speed of vesicle replenishment are also reduced in cells lacking ribbons. Our findings suggest that synaptic ribbons play a crucial role in enhancing the release of vesicles and maintaining proper visual responses.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Katsunori Kobayashi, Kisako Shikano, Mahomi Kuroiwa, Mio Horikawa, Wakana Ito, Akinori Nishi, Eri Segi-Nishida, Hidenori Suzuki
Summary: The activation of D(1)Rs by noradrenaline is crucial for the antidepressant effects, suggesting a potential therapeutic target for depressive disorders. Increased voluntary exercise enhances the synaptic potentiation mediated by D(1)Rs, indicating a distinct role of noradrenaline-D(1)R signaling. This pathway may play a critical role in determining the responsiveness to antidepressant drugs.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Fan Fan, Yumei Wu, Manami Hara, Adam Rizk, Chen Ji, Dan Nerad, Natalia Tamarina, Xuelin Lou
Summary: This study revealed the crucial role of dynamins in endocytosis and secretion capacity of pancreatic beta cells, indicating that deficiency in dynamin-mediated endocytosis can lead to impaired insulin secretion, increasing the risk of endocrine dysfunction and diabetes.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Takayuki Ikeda, Yoshino Yoshitake, Yasuo Yoshitomi, Hidehito Saito-Takatsuji, Yasuhito Ishigaki, Hideto Yonekura
Summary: This study revealed that EPAC2 affects the morphology and migration of microvascular endothelial cells, and is involved in the termination and proper network formation of vascular tubes.
SCIENTIFIC REPORTS
(2021)
Article
Biology
Chao Tan, Giovanni de Nola, Claire Qiao, Cordelia Imig, Richard T. Born, Nils Brose, Pascal S. Kaeser
Summary: Active zone-anchored Munc13 and non-active zone-anchored Munc13 may independently support vesicle fusion. Removal of RIM and ELKS disrupts vesicle docking, but other ultrastructural features remain near-normal.
Review
Neurosciences
Meishar Shahoha, Ronni Cohen, Yoav Ben-Simon, Uri Ashery
Summary: Cyclic adenosine monophosphate (cAMP) is a key second messenger involved in synaptic plasticity. In the hippocampal mossy fiber (MF) synapse, cAMP mediates long-term changes to synaptic efficacy through the activation of the protein kinase A (PKA) cascade. This review summarizes the current knowledge on cAMP catalysts, PKA-dependent molecular cascades, and non-canonical cAMP-dependent but PKA-independent pathways in MF terminals. Understanding the molecular mechanisms underlying MF plasticity could provide insights into the relationship between transcriptional and computational levels in different brain regions.
FRONTIERS IN SYNAPTIC NEUROSCIENCE
(2022)
Article
Neurosciences
Shan-Xue Jin, Lei Liu, Shaomin Li, Angela L. Meunier, Dennis J. Selkoe
Summary: Early cognitive impairment in Alzheimer's disease might be caused by synaptic dysfunction resulted from the accumulation of oligomeric assemblies of amyloid beta-protein (Aβ). This study found that Aβ oligomers inhibited presynaptic transmission and LTP at the mossy fiber synapses. Activation of beta 1 and beta 2 adrenergic receptors and downstream cAMP/PKA signaling pathway prevented this inhibition, and the cGMP/PKG signaling pathway also had a protective effect.
NEUROBIOLOGY OF DISEASE
(2022)
Article
Neurosciences
Toshihiro Nomura, Nicole A. Hawkins, Jennifer A. Kearney, Alfred L. George, Anis Contractor
JOURNAL OF PHYSIOLOGY-LONDON
(2019)
Review
Pediatrics
Sean M. Riordan, Steven M. Shapiro
PEDIATRIC RESEARCH
(2020)
Review
Pediatrics
Steven M. Shapiro, Sean M. Riordan
PEDIATRIC RESEARCH
(2020)
Article
Pediatrics
Silvia Gazzin, Sean M. Riordan
PEDIATRIC RESEARCH
(2020)
Article
Cell Biology
Pierre De Rossi, Toshihiro Nomura, Robert J. Andrew, Nicolas Y. Masse, Vandana Sampathkumar, Timothy F. Musial, Ari Sudwarts, Aleksandra J. Recupero, Thomas Le Metayer, Mitchell T. Hansen, Ha-Na Shim, Sofia V. Krause, David J. Freedman, Vytas P. Bindokas, Narayanan Kasthuri, Daniel A. Nicholson, Anis Contractor, Gopal Thinakaran
Article
Biochemistry & Molecular Biology
Timothy J. Hark, Nalini R. Rao, Charlotte Castillon, Tamara Basta, Samuel Smukowski, Huan Bao, Arun Upadhyay, Ewa Bomba-Warczak, Toshihiro Nomura, Eileen T. O'Toole, Garry P. Morgan, Laith Ali, Takashi Saito, Christelle Guillermier, Takaomi C. Saido, Matthew L. Steinhauser, Michael H. B. Stowell, Edwin R. Chapman, Anis Contractor, Jeffrey N. Savas
Summary: Protein turnover impairment at presynaptic terminals, particularly with synaptic vesicle-associated proteins, is observed at early stages of Alzheimer's disease. These impaired proteins interact with APP and Ab, leading to vulnerability of presynaptic terminals and manifestation of initial AD etiology.
Article
Clinical Neurology
Sherouk A. Abdelmoity, Ayman A. Abdelmoity, Sean M. Riordan, Christian Kaufman, Jean-Baptiste Le Pichon, Ahmed Abdelmoity
Summary: This study assessed the efficacy and tolerability of auto-stimulation VNS models in pediatric patients with LGS, showing that at 24 months post implantation, most patients experienced significant seizure reduction and improvements in quality of life measures. The most commonly reported adverse events were dysphonia, paresthesia, and shortness of breath, which were all tolerated and subsided within 24 months.
SEIZURE-EUROPEAN JOURNAL OF EPILEPSY
(2021)
Article
Behavioral Sciences
Jian Xu, John J. Marshall, Stephen Kraniotis, Toshihiro Nomura, Yongling Zhu, Anis Contractor
Summary: The study reveals that loss of mGluR5 has significant effects on social interaction and motor behavior, while not affecting self-grooming. Mice with mGluR5 ko show almost complete abolition of digging and marble burying behaviors, and impaired social interaction behavior.
BEHAVIOURAL BRAIN RESEARCH
(2021)
Article
Neurosciences
Landon J. Rohowetz, Marc E. Mardelli, R. Scott Duncan, Sean M. Riordan, Peter Koulen
Summary: In the glaucoma mouse model, iris pigment dispersion is positively correlated with increased intraocular pressure, while corneal calcification does not seem to play a role in the development of elevated IOP.
FRONTIERS IN NEUROSCIENCE
(2022)
Review
Cell Biology
Toshihiro Nomura
Summary: The imbalance of excitatory-inhibitory (E-I) balance has been implicated in various neurological and psychiatric diseases, including autism spectrum disorder (ASD). Fragile X syndrome (FXS) is a single-gene disorder that is the most common known cause of ASD, and deficits in inhibitory circuits in FXS tip the E-I balance towards excitation. Manipulating the activity of inhibitory interneurons can ameliorate symptoms in FXS, suggesting the potential for targeting interneurons to correct disrupted E-I balance in FXS.
Article
Neurosciences
R. Scott Duncan, Sean M. Riordan, Conner W. Hall, Andrew J. Payne, Kent D. Chapman, Peter Koulen
Summary: This study found that sublethal oxidative stress increases the expression of eCB proteins and enhances the nuclear localization of FAAH. This is important for further understanding the role of eCB metabolizing proteins and eCB receptors in defending against oxidative stress.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Ophthalmology
Jacob K. Player, Sean M. Riordan, R. Scott Duncan, Peter Koulen
Summary: Glaucoma is the second leading cause of blindness worldwide, and its pathogenesis still has many unanswered questions. This study found that gene expression in glaucoma patients changed, indicating the possibility of using peripheral biomarkers for glaucoma diagnosis and staging. Additionally, the study also discovered the impact of Hepatitis C virus infection on the expression of glaucoma biomarker genes.
CLINICAL OPHTHALMOLOGY
(2022)
Meeting Abstract
Ophthalmology
Landon James Rohowetz, Sean Riordan, Peter Koulen
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2021)
Meeting Abstract
Pediatrics
Tina Slusher, Isa Abdulkadir, Udochukwu Diala, Akinyemi Ofakunrin, Mohd Abdussalam, A. Sabo Umar, Binta Wudil Jibir, Steven Shapiro, Sean Riordan, Alan Kleinfield, Stephen Oguche
Article
Cell & Tissue Engineering
Andrew S. Welleford, Jorge E. Quintero, Nader El Seblani, Eric Blalock, Sumedha Gunewardena, Steven M. Shapiro, Sean M. Riordan, Peter Huettl, Zain Guduru, John A. Stanford, Craig G. van Horne, Greg A. Gerhardt
CELL TRANSPLANTATION
(2020)