Review
Biochemistry & Molecular Biology
Tzu-Hsin Huang, Ming-Chi Lai, Yu-Shiue Chen, Chin-Wei Huang
Summary: Status epilepticus (SE) is a neurological emergency with high mortality rate. The downregulation of GABAA receptors and upregulation of NMDA and AMPA receptors are the most widely accepted hypothesis underlying BZD resistance.
Review
Biochemistry & Molecular Biology
Takashi Hosaka, Hiroshi Tsuji, Shin Kwak
Summary: A-to-I RNA editing is a critical post-transcriptional modification that can alter protein function and is implicated in the pathogenesis of neurological diseases, particularly ALS. The dysregulation of RNA editing at the Q/R site of GluA2 and the downregulation of ADAR2 in motor neurons suggest potential therapeutic targets for ALS, including Ca2+-permeable AMPA receptors. Gene therapy targeting RNA editing dysregulation has emerged as a promising therapeutic approach for ALS and other neurological diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Behavioral Sciences
Ahmad Tarmizi Che Has
Summary: Status epilepticus is a neurological disorder with various neuropathological conditions and presentations. Animal models, particularly the chemically induced pilocarpine model, have been used to understand and replicate its manifestations. However, there are challenges in inducing the model, such as morbidity and mortality rates. Modifications, including dose fractionation and lithium-pilocarpine model, have been introduced to tackle these issues. Despite the drawbacks, this model has proven its relevance and has been improved since its discovery in 1983.
BEHAVIOURAL BRAIN RESEARCH
(2023)
Article
Neurosciences
Aurelie Hanin, Paul Baudin, Sophie Demeret, Delphine Roussel, Sarah Lecas, Elisa Teyssou, Maria Damiano, David Luis, Virginie Lambrecq, Valerio Frazzini, Maxens Decavele, Isabelle Plu, Dominique Bonnefont-Rousselot, Randa Bittar, Foudil Lamari, Vincent Navarro
Summary: This study focused on analyzing the changes in brain cholesterol homeostasis associated with severe status epilepticus (SE), revealing a decrease in 24-hydroxycholesterol levels in SE patients and mouse models, accompanied by increased cholesterol synthesis. The findings suggest that CYP46A1 inhibition after SE could lead to cerebral cholesterol accumulation, which is known to be excitotoxic for neuronal cells and might contribute to the neurological sequelae observed following SE, highlighting a novel pathophysiological pathway involved in SE excitotoxicity.
NEUROBIOLOGY OF DISEASE
(2021)
Review
Oncology
Valentina Frezza, Lidia Chellini, Arianna Del Verme, Maria Paola Paronetto
Summary: Recent evidence has shown that RNA editing, in addition to somatic mutations and alternative splicing changes, plays a significant role in altering genetic information in a dynamic fashion. This form of post-transcriptional RNA modification is closely associated with the development of various human diseases, including cancer, by regulating various cellular processes. Studies on the impact of RNA editing in cancer transformation are gaining increasing interest, particularly in relation to cell proliferation, differentiation, invasion, stemness, and drug resistance.
Article
Neurosciences
Efrat Shavit-Stein, Shani Berkowitz, Tal Davidy, Uri Fennig, Shani Guly Gofrit, Amir Dori, Nicola Maggio
Summary: This study evaluated the effects of thrombin pathway inhibition in a mice model of SE and found that thrombin is involved in memory impairment and cognitive dysfunction. Inhibiting the thrombin pathway can prevent cognitive impairment and reduce neuronal damage.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Bernadette Liemberger, Johannes Bischof, Michael Ablinger, Stefan Hainzl, Eva M. Murauer, Nina Lackner, Patricia Ebner, Thomas Kocher, Alexander Nystroem, Verena Wally, Elisabeth Mayr, Christina Guttmann-Gruber, Josefina Pinon Hofbauer, Johann W. Bauer, Ulrich Koller
Summary: Mutations in the COL7A1 gene can cause skin problems by affecting type VII collagen (C7) in the basement membrane zone. The researchers used an RNA therapy called spliceosome-mediated RNA trans-splicing (SMaRT) to correct mutations in COL7A1. They successfully corrected mutations in RDEB keratinocytes and RDEB skin equivalents by introducing a repair molecule called RTM-S6m.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Audiology & Speech-Language Pathology
Dalian Ding, Weidong Qi, Haiyan Jiang, Richard Salvi
Summary: Excessive release of glutamate at the inner hair cell-type I auditory nerve synapse leads to excitotoxicity, with potential damage extending to the spiral ganglion soma. Developmental regulation of glutamate receptors alters the pattern of excitotoxic damage, with different receptor expressions in early postnatal versus adult cochlear cultures impacting the extent of damage. AMPAR and KAR expression on specific structures closely correlates with cochlear excitotoxic damage.
Article
Medicine, General & Internal
Chung-Ming Huang, Yu-Chia Chen, I-Lu Lai, Hong-Da Chen, Po-Hao Huang, Siang-Jyun Tu, Ya-Ting Lee, Ju-Chen Yen, Chia-Li Lin, Ting-Yuan Liu, Jan-Gowth Chang
Summary: Hyperuricemia and gout are common metabolic disorders with increasing incidence worldwide. This study found that RNA modifications, editing, and splicing play roles in gout development, and the findings may contribute to the development of new diagnostic and therapeutic strategies.
FRONTIERS IN MEDICINE
(2022)
Article
Pharmacology & Pharmacy
Mohamed Z. Habib, Esraa M. Elnahas, Yasmin M. Aboul-Ela, Mai A. Ebeid, Marwa Tarek, Doaa R. Sadek, Eman A. Negm, Dina A. Abdelhakam, Sawsan Aboul-Fotouh
Summary: Several reports suggest that calcium permeable AMPA glutamate receptors with RNA hypo-editing at the GluA2 Q/R site and excitotoxicity-mediated neuronal death play a role in the pathogenesis of neurological disorders including autism spectrum disorder (ASD). This study examined the effects of risperidone treatment on Adar2 expression, GluA2 editing, oxidative/nitrosative stress, and neuronal death in a rat model of ASD. The results showed that risperidone improved behavioral deficits and increased Adar2 expression and GluA2 editing, while reducing oxidative/nitrosative stress and neurodegeneration.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Petr Fabera, Libor Uttl, Hana Kubova, Grygoriy Tsenov, Pavel Mares
Summary: LiCl/pilocarpine status epilepticus induces changes in ADK isoform expression and inhibiting ADK with 5-ITU affects hippocampal excitability. The study shows that SE leads to decreased excitability in immature rats 3 days after induction, followed by increased excitability after 20 days. 5-ITU demonstrates inhibitory effects on hippocampal excitability in SE rats. ADK isoforms also show altered expression levels in SE rats, indicating their involvement in hippocampal excitability and brain development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Yang Pan, John W. Phillips, Beatrice D. Zhang, Miyako Noguchi, Eric Kutschera, Jami McLaughlin, Pavlo A. Nesterenko, Zhiyuan Mao, Nathanael J. Bangayan, Robert Wang, Wendy Tran, Harry T. Yang, Yuanyuan Wang, Yang Xu, Matthew B. Obusan, Donghui Cheng, Alex H. Lee, Kathryn E. Kadash-Edmondson, Ameya Champhekar, Cristina Puig-Saus, Antoni Ribas, Robert M. Prins, Christopher S. Seet, Gay M. Crooks, Owen N. Witte, Yi Xing
Summary: This study describes a computational platform called IRIS that can discover tumor antigens derived from alternative splicing, providing potential targets for TCR and CAR-T immunotherapies. Through the analysis of transcriptomics and immuno-peptidomics data, the study demonstrates that the predicted targets by IRIS can bind with HLA molecules. The study illustrates the contribution of alternative splicing to the repertoire of tumor antigens and demonstrates the utility of IRIS in discovering AS-derived antigens and expanding cancer immunotherapies.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Plant Sciences
Yanwei Wang, Zhimin Yang, Meng Zhang, Pengfei Ai
Summary: This study identified the crucial role of the rice SSA1 gene in chloroplast biogenesis. SSA1 regulates early chloroplast development and is involved in RNA editing and intron splicing. These findings contribute to the understanding of molecular mechanisms underlying chloroplast generation.
Article
Neurosciences
Zhongrui Liu, Ziting Zhu, Yan He, Qiyun Kang, Fei Li, Wenlong Zhang, Yuehua He, Yuwan Lin, Baoyi Huang, Mingshu Mo, Pingyi Xu, Xiaoqin Zhu
Summary: The novel H2S donor synthesized in this study has been shown to effectively reduce seizures in animal models and in vitro experiments by regulating microglial inflammatory response. This suggests that the novel H2S donor may have a new mechanism and potential therapeutic strategy for anti-seizures.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Nagwa I. Shehata, Mai A. Abdelsamad, Hebat Allah A. Amin, Nermin A. H. Sadik, Amira A. Shaheen
Summary: This study aimed to evaluate the potential neuroprotective effects of ketogenic diet (KD) against neuronal disruptions induced by status epilepticus (SE). Results showed that KD could improve neurotransmitter balance, oxidative stress and inflammatory response, reduce neuronal damage, and preserve neuronal integrity.
JOURNAL OF FOOD BIOCHEMISTRY
(2022)
Article
Medicine, Research & Experimental
Ilaria Grossi, Annalisa Radeghieri, Lucia Paolini, Vanessa Porrini, Andrea Pilotto, Alessandro Padovani, Alessandra Marengoni, Alessandro Barbon, Arianna Bellucci, Marina Pizzi, Alessandro Salvi, Giuseppina De Petro
Summary: This exploratory study focused on investigating the differential profile of circulating miR-34a-5p in Parkinson's disease (PD) patients and found that miR-34a-5p was significantly up-regulated in small EVs from PD patients. The study suggests that miR-34a-5p levels in pure SEVs may have a good diagnostic performance in discriminating PD patients from control subjects, and that these levels are associated with disease severity and depression symptoms.
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
(2021)
Article
Clinical Neurology
Mohammed E. A. Elhussiny, Giulia Carini, Jessica Mingardi, Paolo Tornese, Nathalie Sala, Federica Bono, Chiara Fiorentini, Luca La Via, Maurizio Popoli, Laura Musazzi, Alessandro Barbon
Summary: The study found that ketamine, as an antidepressant, can affect protein expression and phosphorylation levels of glutamate receptors in the hippocampus of rats in a depression model, especially at synaptic membranes. Chronic stress exposure induces hypofunction of activity-dependent glutamatergic synaptic transmission in all animals, while the selective modulation of mGlu2 receptor may be associated with stress vulnerability.
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
(2021)
Article
Biochemistry & Molecular Biology
Chiara Magri, Erika Vitali, Sara Cocco, Edoardo Giacopuzzi, Marco Rinaudo, Paolo Martini, Alessandro Barbon, Claudio Grassi, Massimo Gennarelli
Summary: This study provides a comprehensive molecular characterization of the 3xTg-AD mouse and suggests that blood gene expression may serve as new biomarkers for identifying AD progression and treatment effects.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Geriatrics & Gerontology
Giulia Carini, Laura Musazzi, Francesco Bolzetta, Alberto Cester, Chiara Fiorentini, Alessandro Ieraci, Stefania Maggi, Maurizio Popoli, Nicola Veronese, Alessandro Barbon
Summary: Frailty and cognitive impairment are common in older individuals, with age being the main risk factor for both conditions. MicroRNAs have been proposed as potential biomarkers and molecular effectors in physiological and pathological aging processes, with some miRNAs showing promise in being associated with frailty and cognitive impairment.
FRONTIERS IN AGING NEUROSCIENCE
(2021)
Article
Genetics & Heredity
Giulia Carini, Jessica Mingardi, Francesco Bolzetta, Alberto Cester, Andrea Bolner, Giampietro Nordera, Luca La Via, Alessandro Ieraci, Isabella Russo, Stefania Maggi, Stefano Calza, Maurizio Popoli, Nicola Veronese, Laura Musazzi, Alessandro Barbon
Summary: The study aimed to identify potential frailty biomarkers and candidate mechanisms, finding two miRNAs that significantly differentiate frail patients from robust subjects. The potential molecular mechanisms and cellular pathways regulated by these miRNAs in frailty were further explored using bioinformatics tools.
Article
Neurosciences
Jessica Mingardi, Luca La Via, Paolo Tornese, Giulia Carini, Kalevi Trontti, Mara Seguini, Daniela Tardito, Federica Bono, Chiara Fiorentini, Leonardo Elia, Iiris Hovatta, Maurizio Popoli, Laura Musazzi, Alessandro Barbon
Summary: Recent research has shown that decreased levels of miR-9-5p in the hippocampus is associated with vulnerability to Chronic Mild Stress (CMS) in rats, and acute subanesthetic ketamine can restore these levels in just 24 hours. The expression of miR-9-5p is inversely correlated with the anhedonic phenotype.
NEUROBIOLOGY OF STRESS
(2021)
Article
Pharmacology & Pharmacy
Nathalie Sala, Caterina Paoli, Tiziana Bonifacino, Jessica Mingardi, Emanuele Schiavon, Luca La Via, Marco Milanese, Paolo Tornese, Ashok K. Datusalia, Jessica Rosa, Roberta Facchinetti, Giulia Frumento, Giulia Carini, Floramarida Salerno Scarzella, Caterina Scuderi, Lia Forti, Alessandro Barbon, Giambattista Bonanno, Maurizio Popoli, Laura Musazzi
Summary: Stress is a major risk factor for psychiatric disorders, including PTSD. Ketamine has been found to block the detrimental effects of acute stress on the glutamate system and improve depressive, anxious, and fear extinction behaviors in rats.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jessica Mingardi, Caterina Paoli, Luca La Via, Giulia Carini, Paulina Misztak, Carlo Cifani, Maurizio Popoli, Alessandro Barbon, Laura Musazzi
Summary: Stress is a crucial risk factor for neuropsychiatric disorders, and understanding the mechanisms underlying stress response is important for identifying therapeutic targets. MicroRNAs (miRNAs) have emerged as key regulators in the brain, and miR-135a-5p has been associated with stress response and synaptic mechanisms. This study found that both acute and chronic stress decrease miR-135a-5p levels in the prefrontal cortex (PFC), and the reduction is more pronounced in animals vulnerable to chronic stress. The downregulation of miR-135a-5p affects dendritic spine density and two predicted target genes show increased expression after stress.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Gaia Faustini, Francesca Longhena, Alessia Musco, Federica Bono, Edoardo Parrella, Luca La Via, Alessandro Barbon, Marina Pizzi, Franco Onofri, Fabio Benfenati, Cristina Missale, Maurizio Memo, Daniela Zizioli, Arianna Bellucci
Summary: This study suggests that polymorphisms in the Synapsin III (Syn III) gene may play a role in the development of ADHD and the response to medication. It was found that Syn III is involved in the early stages of dopaminergic neuron development, and this function is conserved in vertebrates. Additionally, in mammals, Syn III regulates dendrite development stimulated by BDNF and Cdk5.
Article
Biochemistry & Molecular Biology
Lia Forti, Elona Ndoj, Jessica Mingardi, Emanuele Secchi, Tiziana Bonifacino, Emanuele Schiavon, Giulia Carini, Luca La Via, Isabella Russo, Marco Milanese, Massimo Gennarelli, Giambattista Bonanno, Maurizio Popoli, Alessandro Barbon, Laura Musazzi
Summary: Traumatic stress is a significant risk factor for psychiatric disorders. This study investigates the effects of acute footshock stress and ketamine on the glutamatergic synaptic plasticity in the prefrontal cortex. The findings suggest that acute stress and ketamine induce changes in dopamine-dependent long-term potentiation (LTP) as well as ionotropic glutamate receptor subunit expression and localization. Further research is needed, but this initial report supports the potential benefit of acute ketamine in mitigating the impact of acute traumatic stress.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Psychiatry
Tiziana Bonifacino, Jessica Mingardi, Roberta Facchinetti, Nathalie Sala, Giulia Frumento, Elona Ndoj, Marta Valenza, Caterina Paoli, Alessandro Ieraci, Carola Torazza, Matilde Balbi, Michele Guerinoni, Nadeem Muhammad, Isabella Russo, Marco Milanese, Caterina Scuderi, Alessandro Barbon, Luca Steardo, Giambattista Bonanno, Maurizio Popoli, Laura Musazzi
Summary: Stress is a major risk factor for psychiatric disorders, but little is known about the mechanisms of vulnerability to acute stressors. In this study, a new animal model of resilience/vulnerability to acute footshock stress in rats was generated and used to identify early determinants of maladaptive response related to behavioral vulnerability to stress.
TRANSLATIONAL PSYCHIATRY
(2023)
Article
Genetics & Heredity
Paolo Martini, Jessica Mingardi, Giulia Carini, Stefania Mattevi, Elona Ndoj, Luca La Via, Chiara Magri, Massimo Gennarelli, Isabella Russo, Maurizio Popoli, Laura Musazzi, Alessandro Barbon
Summary: Stress is a major risk factor for psychiatric disorders, and the response to stress involves the regulation of transcriptional programs. In this study, we analyzed the gene expression changes in the prefrontal cortex (PFC) of rats exposed to acute footshock stress. We found alterations in neuronal pathways, glia development, glia-neuron networking, and synaptic function. Furthermore, specific transcription factors were identified as potential master regulators of the acute stress response.
Article
Biochemistry & Molecular Biology
Jessica Mingardi, Elona Ndoj, Tiziana Bonifacino, Paulina Misztak, Matteo Bertoli, Luca La Via, Carola Torazza, Isabella Russo, Marco Milanese, Giambattista Bonanno, Maurizio Popoli, Alessandro Barbon, Laura Musazzi
Summary: Stress is a major risk factor for neuropsychiatric disorders, including major depressive disorder. Using a rat model of depression, researchers found that chronic stress induced morphological, functional, and molecular changes in the hippocampus, which were reversed by acute subanesthetic ketamine. In this study, they focused on the medial prefrontal cortex (mPFC) and found that most changes induced by stress were observed in vulnerable animals and rescued by ketamine, while others were only found in resilient animals or induced by ketamine treatment. Importantly, these changes were specific to the mPFC and not previously demonstrated in the hippocampus. Overall, the results suggest that acute antidepressant ketamine can reverse stress-induced glutamatergic changes in a brain-area-specific manner.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Elena Cannone, Valeria Guglielmi, Giulia Marchetto, Chiara Tobia, Barbara Gnutti, Barbara Cisterna, Paola Tonin, Alessandro Barbon, Gaetano Vattemi, Marco Schiavone
Summary: Myofibrillar myopathies (MFMs) are a group of hereditary neuromuscular disorders characterized by myofibrillar derangement, Z-disk disintegration, and protein aggregation. Mutations in genes encoding structural proteins or molecular chaperones are implicated in MFM pathogenesis. In this study, transgenic zebrafish overexpressing mutant MYOT or CRYAB genes showed severe morphological defects and protein aggregation, resembling human myofibrillar myopathy. These findings suggest that zebrafish can serve as a useful model for studying the pathogenesis of MFM and identifying potential therapeutic targets.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Laura Musazzi, Jessica Mingardi, Alessandro Ieraci, Alessandro Barbon, Maurizio Popoli
Summary: Stress is a significant risk factor for psychiatric disorders, but the mechanisms underlying the long-term effects of stress on the development of these disorders are still unknown. Epigenetic mechanisms, including microRNAs, play a crucial role in the effects of the environment on brain gene expression and behavior. MicroRNAs have been shown to regulate gene expression in the brain, affecting homeostasis and potentially influencing adaptive or maladaptive brain changes. While microRNA-based diagnostics and therapeutics have made progress in other fields, their development for brain disorders lags behind.
MOLECULAR PSYCHIATRY
(2023)
