Article
Clinical Neurology
Tiago F. Outeiro, Peter Heutink, Erwan Bezard, Angela M. Cenci
Summary: Parkinson's disease is primarily characterized by movement disorders associated with the loss of dopaminergic neurons. However, it is now understood as a complex condition with multiple nonmotor features, involving various protein inclusions. Familial forms of PD have provided insights into the molecular pathways leading to neurodegeneration, adding complexity to the issue. Models using patient-derived cells and animal models, combined with current technological tools, are proposed to expand understanding and identify therapeutic strategies for PD.
MOVEMENT DISORDERS
(2021)
Article
Biology
Ziqi Yu, Xiaoyang Han, Wenjing Xu, Jie Zhang, Carsten Marr, Dinggang Shen, Tingying Peng, Xiao-Yong Zhang, Jianfeng Feng
Summary: This study proposes a domain-adaptive and semi-supervised deep neural network called Brain Extraction Net (BEN) for extracting brain tissues across species, MRI modalities, and MR scanners. Compared to conventional toolboxes, BEN demonstrates superior robustness, accuracy, and generalizability.
Article
Biochemical Research Methods
Shaochong Zhang, Lu Chen, Yining Zhang, Dong Fang
Summary: The development of CRISPR/Cas genome editing tools has led to transformative applications in the field of neurological disorders, with the CRISPR-Cas13 system showing immense potential for cell fate conversion therapies, particularly in converting glia to neurons. The introduction of AAV-based CRISPR-Cas13 system has shown promising effects in treating animal models of neurological diseases.
Article
Biochemical Research Methods
Rishi Rajalingham, Michael Sorenson, Reza Azadi, Simon Bohn, James J. DiCarlo, Arash Afraz
Summary: The development of Opto-Array, a chronically implantable array of light-emitting diodes, has shown to be effective for behavioral optogenetic applications in large brains like nonhuman primates. Optogenetic silencing with Opto-Array in the macaque primary visual cortex results in reliable retinotopic visual deficits, demonstrating its potential for studying complex behaviors in primate brains.
Review
Immunology
Dan Li, Shuang Yu, Yu Long, Ai Shi, Jie Deng, Yin Ma, Jing Wen, Xiaoqiu Li, Songyu Liu, Yulu Zhang, Jinyan Wan, Nan Li, Rui Ao
Summary: Neurological and psychiatric disorders are chronic diseases that have a significant impact on patients' mental and physical health. Tryptophan metabolism plays a crucial role in the development of these disorders. This paper discusses the relationship between tryptophan metabolism and neurological and psychiatric disorders, focusing on the metabolites TRYCATs and their involvement in pathological processes. It also reviews the factors that regulate tryptophan metabolism and its downstream effects, as well as the current understanding and effective drugs for treating neurological and psychiatric disorders. Future research prospects in this field are also considered.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Naohisa Miyakawa, Yuji Nagai, Yukiko Hori, Koki Mimura, Asumi Orihara, Kei Oyama, Takeshi Matsuo, Ken-ichi Inoue, Takafumi Suzuki, Toshiyuki Hirabayashi, Tetsuya Suhara, Masahiko Takada, Makoto Higuchi, Keisuke Kawasaki, Takafumi Minamimoto
Summary: Pharmacological and surgical treatments of epilepsy have limited success, therefore a more targeted and on-demand approach is desired. The authors demonstrate the use of inhibitory chemogenetics to attenuate cortical seizures and subsequent convulsions in nonhuman primates. These results highlight the efficacy of DREADDs for treating epilepsy in a primate model.
NATURE COMMUNICATIONS
(2023)
Review
Neurosciences
Lihong Guan, Yawei Han, Ciqing Yang, Suxiang Lu, Jiang Du, Han Li, Juntang Lin
Summary: Neurological disorders, with complex etiology and difficult treatment, are hindered by poor understanding of their pathogenic mechanisms. The advancement of CRISPR-Cas9 technology in precise gene editing has accelerated basic biological research, potentially leading to the development of new therapies for neurological disorders.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Biochemical Research Methods
Yicheng Long, Thomas R. Cech
Summary: The use of CRISPR genome editing has greatly advanced mutagenesis studies in human iPSCs, enabling precise gene manipulation for studying physiological functions, disease modeling, drug screening, and therapeutic development. However, comprehensive strategic designs are necessary to consider potential side effects of CRISPR editing. This study presents novel and highly efficient strategies for introducing mutations in human iPSCs, including step-by-step protocols and examples of successful application in different cell types.
Review
Gastroenterology & Hepatology
Jessica Faccioli, Silvia Nardelli, Stefania Gioia, Oliviero Riggio, Lorenzo Ridola
Summary: HCV infection can lead to various extrahepatic manifestations, such as neurological symptoms, in addition to liver-related issues. Successful treatment relies on achieving sustained virological response, and neurological symptoms may be irreversible if there is organic liver damage.
WORLD JOURNAL OF GASTROENTEROLOGY
(2021)
Review
Behavioral Sciences
Francesca Longhena, Gaia Faustini, Viviana Brembati, Marina Pizzi, Fabio Benfenati, Arianna Bellucci
Summary: Synapsins are phosphoproteins involved in neuronal development and neurotransmitter release, with multiple functions in synaptic formation, vesicle mobilization, and recycling. Dysregulation in their expression, modifications, or encoding genes can lead to brain network dysfunction and psychiatric or neurological disorders. This review provides the latest information on Syns structure, function, physiology, and their role in central nervous system disorders.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2021)
Article
Cell & Tissue Engineering
Huan Zou, Mingfeng Guan, Yundong Li, Fang Luo, Wenyuan Wang, Yiren Qin
Summary: This study successfully corrected the genetic mutation of Achondroplasia patients using stem cells and gene editing technology, restoring their chondrogenic differentiation ability and providing an important theoretical and experimental basis for Achondroplasia research and treatment.
STEM CELL RESEARCH & THERAPY
(2021)
Review
Chemistry, Medicinal
Cinthia C. S. Menezes da Silveira, Diandra A. Luz, Carla C. S. da Silva, Rui D. S. Prediger, Manoela D. Martins, Marco A. T. Martins, Eneas A. Fontes-Junior, Cristiane S. F. Maia
Summary: Propolis, a honeybee product, containing compounds such as CAPE and pinocembrin, have shown promising therapeutic purposes in treating neurological disturbances and psychiatric disorders. The molecular mechanisms underlying these effects may involve inhibition of the pro-inflammatory cascade, antioxidant activity, and positive neurotrophic modulatory effects.
MEDICINAL RESEARCH REVIEWS
(2021)
Article
Biology
Tao Ye, Yangyang Duan, Hayley W. S. Tsang, He Xu, Yuewen Chen, Han Cao, Yu Chen, Amy K. Y. Fu, Nancy Y. Ip
Summary: Researchers demonstrate a simple and precise method to simultaneously generate iPSC lines with different gene dosages using paired Cas9 nickases. As proof-of-concept they apply this method to examining amyloid precursor protein gene dosage effects in an Alzheimer's disease patient-derived iPSC line. Their method could potentially advance what we know about disease mechanisms and assist with gene therapy development.
COMMUNICATIONS BIOLOGY
(2021)
Review
Psychiatry
Christina Michalski, Zhexing Wen
Summary: Communication between the immune and nervous systems is crucial for brain development and homeostasis. Using iPSC technology, clinically relevant models of the central nervous system can be developed to study neuro-immune interactions. These models provide insights into the effects of environmental stressors and genetic risk factors on neuronal and glial cell function.
FRONTIERS IN PSYCHIATRY
(2023)
Review
Biochemistry & Molecular Biology
Giulia Paolini Sguazzi, Valentina Muto, Marco Tartaglia, Enrico Bertini, Claudia Compagnucci
Summary: Gene therapy traditionally used viral vectors for gene delivery, but recent advances in stem cell and gene therapy fields have revolutionized this approach, particularly with the combination of stem cell replacement therapy and gene editing technology, leading to a new era in gene therapy for neurological disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Editorial Material
Neurosciences
G. Sanacora, H. Heimer, D. Hartman, S. J. Mathew, M. Frye, C. Nemeroff, R. Robinson Beale
NEUROPSYCHOPHARMACOLOGY
(2017)
Article
Biology
Erinn S. Gideons, Pei-Yin Lin, Melissa Mahgoub, Ege T. Kavalali, Lisa M. Monteggia
Editorial Material
Multidisciplinary Sciences
Francis S. Lee, Hakon Heimer, Jay N. Giedd, Edward S. Lein, Nenad Sestan, Daniel R. Weinberger, B. J. Casey
Article
Biology
Patricia M. Horvath, Michelle K. Piazza, Lisa M. Monteggia, Ege T. Kavalali
Article
Neurosciences
Ji-Woon Kim, Anita E. Autry, Elisa S. Na, Megumi Adachi, Carl Bjorkholm, Ege T. Kavalali, Lisa M. Monteggia
Summary: This study shows that MeCP2 phosphorylation at a specific site downstream of BDNF is essential for the sustained antidepressant effects of ketamine and scopolamine, and plays a critical role in long-term regulation of synaptic strength. These findings highlight the importance of MeCP2 and associated synaptic plasticity in mediating sustained antidepressant effects of ketamine and scopolamine.
NATURE NEUROSCIENCE
(2021)
Review
Biochemistry & Molecular Biology
Camille S. Wang, Ege T. Kavalali, Lisa M. Monteggia
Summary: This review examines the importance of spatial and temporal factors on BDNF activity, particularly in processes such as synaptogenesis, plasticity, and psychiatric disorder treatment. Understanding the fundamental physiology of BDNF and new approaches to control its signaling in time and space can lead to improved therapeutics and patient outcomes.
Article
Cell Biology
Kanzo Suzuki, Ji-Woon Kim, Elena Nosyreva, Ege T. Kavalali, Lisa M. Monteggia
Summary: Acute inhibition of eEF2K activity induces rapid synaptic scaling in the hippocampus, while RA signaling pathway can also elicit similar synaptic scaling independently of eEF2K function. Activation of RAR alpha by retinoic acid leads to rapid antidepressant effects similar to ketamine.
Article
Biology
Camille S. Wang, Natali L. Chanaday, Lisa M. Monteggia, Ege T. Kavalali
Summary: This study used a fluorescent probe called iGluSnFR to investigate the organization of action potential-evoked and spontaneous neurotransmitter release within individual synapses. The results showed that action potential-evoked release is more susceptible to photobleaching, while spontaneous release is less affected.
Article
Neurosciences
Patricia M. Horvath, Michelle K. Piazza, Ege T. Kavalali, Lisa M. Monteggia
Summary: Rett syndrome, caused by loss of function mutations in MeCP2, is a leading cause of intellectual disability in females. This study reveals the role of MeCP2 in miRNA regulation and its contribution to regional molecular and synaptic impairments. The upregulation of miR-101a and miR-203 in MeCP2 KO mice in the hippocampus and cortex suggests their involvement in Rett syndrome pathophysiology. Furthermore, miR-101a was found to broadly regulate synapse function in the hippocampus. These findings highlight the importance of regional alterations in miRNA expression and its impact on synaptic function.
Review
Biochemistry & Molecular Biology
Ji-Woon Kim, Kanzo Suzuki, Ege T. Kavalali, Lisa M. Monteggia
Summary: Acute administration of (R,S)-ketamine produces rapid and sustained antidepressant effects by blocking NMDA receptors and inducing a novel form of synaptic plasticity in the hippocampus. This triggers downstream signaling events and transcriptional changes that contribute to the antidepressant effects. This review explores the intracellular signaling pathway triggered by ketamine and its connection to synaptic plasticity and sustained antidepressant effects.
TRENDS IN MOLECULAR MEDICINE
(2023)
Article
Biochemical Research Methods
Kanzo Suzuki, Ege T. Kavalali, Lisa M. Monteggia
Summary: This article presents a protocol for analyzing changes in synaptic weights using immunohistochemistry and optical imaging analysis. It involves immunostaining of surface AMPA receptors in mouse brain sections, followed by confocal imaging of the dendritic region of the hippocampal CA1. The synaptic weight analysis is then performed using Fiji/ImageJ and rank order plots.
Review
Neurosciences
Maya Jammoul, Dareen Jammoul, Kevin K. Wang, Firas Kobeissy, Ralph G. Depalma
Summary: This article reviews the possible mechanisms by which traumatic brain injury (TBI) may stimulate the development of opioid use disorder (OUD) and discusses the interaction between these two processes. CNS damage due to TBI appears to drive adverse effects of subsequent OUD, with pain being a risk factor for opioid use after TBI.
BIOLOGICAL PSYCHIATRY
(2024)
Article
Neurosciences
Danusa Mar Arcego, Jan-Paul Buschdorf, Nicholas O'Toole, Zihan Wang, Barbara Barth, Irina Pokhvisneva, Nirmala Arul Rayan, Sachin Patel, Euclides Jose de Mendonca Filho, Patrick Lee, Jennifer Tan, Ming Xuan Koh, Chu Ming Sim, Carine Parent, Randriely Merscher Sobreira de Lima, Andrew Clappison, Kieran J. O'Donnell, Carla Dalmaz, Janine Arloth, Nadine Provencal, Elisabeth B. Binder, Josie Diorio, Patricia Pelufo Silveira, Michael J. Meaney
Summary: This study investigates the impact of environmental influences on mental health by integrating transcriptomic data from animal models with human data. The results suggest that hippocampal glucocorticoid-related transcriptional activity mediates the effects of early adversity on neural mechanisms implicated in psychiatric disorders.
BIOLOGICAL PSYCHIATRY
(2024)
Article
Neurosciences
Milenna T. van Dijk, Ardesheer Talati, Pratik Kashyap, Karan Desai, Nora C. Kelsall, Marc J. Gameroff, Natalie Aw, Eyal Abraham, Breda Cullen, Jiook Cha, Christoph Anacker, Myrna M. Weissman, Jonathan Posner
Summary: This study found that maternal stress is associated with future depressive symptoms and alterations in microstructure of the dentate gyrus (DG) in offspring. These results were consistent across two independent cohorts.
BIOLOGICAL PSYCHIATRY
(2024)
Article
Neurosciences
Josephine C. McGowan, Liliana R. Ladner, Claire X. Shubeck, Juliana Tapia, Christina T. LaGamma, Amanda Anqueira-Gonzalez, Ariana DeFrancesco, Briana K. Chen, Holly C. Hunsberger, Ezra J. Sydnor, Ryan W. Logan, Tzong-Shiue Yu, Steven G. Kernie, Christine A. Denny
Summary: Traumatic brain injury (TBI) leads to fear generalization by altering fear memory traces, and this symptom can be improved with (R,S)-ketamine.
BIOLOGICAL PSYCHIATRY
(2024)