Article
Immunology
Wei Song, Quan Li, Tao Wang, Yuanyuan Li, Tianda Fan, Jianghong Zhang, Qingqing Wang, Jinrong Pan, Qiwen Dong, Zhong Sheng Sun, Yan Wang
Summary: Recent studies have found that CSMD3 deleterious mutations are common in patients with neurodevelopmental disorders. This study shows that Csmd3 disruption leads to retarded development and NDD-related behaviors in mice. Csmd3 deficiency also affects synaptogenesis, neurogenesis, and functional networks in the developing cortex.
BRAIN BEHAVIOR AND IMMUNITY
(2022)
Article
Cell Biology
Kei Hori, Kazumi Shimaoka, Mikio Hoshino
Summary: Neurodevelopmental disorders are a group of neuropsychiatric illnesses that occur during early brain development, affecting cognition, sociability, and sensory and motor functions. AUTS2 is a crucial gene associated with a wide range of neuropsychological disorders, playing a key role in neurodevelopment.
Article
Biochemistry & Molecular Biology
Guodong Chen, Lin Han, Senwei Tan, Xiangbin Jia, Huidan Wu, Yingting Quan, Qiumeng Zhang, Bin Yu, Zhengmao Hu, Kun Xia, Hui Guo
Summary: This study investigates the role of the KMT5B gene in neurodevelopmental disorders, including autism spectrum disorder (ASD), and reveals its essential functions in neuronal development, prenatal neurogenesis, and neuronal migration.
JOURNAL OF GENETICS AND GENOMICS
(2022)
Article
Multidisciplinary Sciences
Ellen F. Mosleth, Christian Alexander Vedeler, Kristian Hovde Liland, Anette McLeod, Gerd Haga Bringeland, Liesbeth Kroondijk, Frode Steingrimsen Berven, Artem Lysenko, Christopher J. Rawlings, Karim El-Hajj Eid, Jill Anette Opsahl, Bjorn Tore Gjertsen, Kjell-Morten Myhr, Sonia Gavasso
Summary: This study identified a common protein signature of MS/CIS patients that is not associated with elevated intrathecal inflammation, suggesting that these patients may suffer from disrupted neural development from an early stage of the disease.
SCIENTIFIC REPORTS
(2021)
Review
Biochemistry & Molecular Biology
Zhiqiang Deng, Xiaoting Zhou, Jia-Hong Lu, Zhenyu Yue
Summary: Autophagy is a cell self-digestion pathway that plays a critical role in maintaining cellular homeostasis and cytoprotection, with diverse physiological functions in various cell types and tissues. In the brain, autophagy integrates into synaptic functions of neurons by recycling damaged materials and exhibits neuroprotective effects. Recent studies have revealed the significant role of autophagy in human brain development and prevention of neurodevelopmental disorders.
CELL AND BIOSCIENCE
(2021)
Article
Biology
John C. O'Donnell, Erin M. Purvis, Kaila V. T. Helm, Dayo O. Adewole, Qunzhou Zhang, Anh D. Le, D. Kacy Cullen
Summary: The Tissue-Engineered Rostral Migratory Stream (TE-RMS) developed by O'Donnell et al. uses astrocyte-like cells derived from adult gingival stem cells to facilitate directed migration of immature neurons and redirect neuroblast migration in athymic rat brains, offering a promising new approach to neuroregenerative medicine.
COMMUNICATIONS BIOLOGY
(2021)
Article
Neurosciences
Alba Ortega-Gasco, Antoni Parcerisas, Keiko Hino, Vicente Herranz-Perez, Fausto Ulloa, Alba Elias-Tersa, Miquel Bosch, Jose Manuel Garcia-Verdugo, Sergi Simo, Lluis Pujadas, Eduardo Soriano
Summary: NCAM2 plays a significant role in the regulation of RGPs during adult neurogenesis and corticogenesis.
Review
Genetics & Heredity
Liliana Rojas-Charry, Leonardo Nardi, Axel Methner, Michael J. Schmeisser
Summary: Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by impairments in social interaction and repetitive behaviors, with mitochondrial dysfunction considered as an important underlying pathogenic factor. However, the pathophysiology of ASD is still not fully understood, with mutations in synaptic genes also playing a role in the disorder. Mitochondria play diverse functions at the synapse, beyond their classical role as energy providers.
JOURNAL OF MOLECULAR MEDICINE-JMM
(2021)
Review
Neurosciences
Cedric Bressan, Armen Saghatelyan
Summary: Neuronal migration is a crucial process in brain development, involving complex interactions between external micro-environmental cues and intrinsic mechanisms. In the adult brain, neuroblasts not only migrate to the olfactory bulb but may also deviate to areas of injury.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Cell & Tissue Engineering
Jian Ma, Xiaoyun Fang, Min Chen, Yao Wang, Li Zhang
Summary: Cell-based therapies have great potential in replacing dying retinal cells. The interaction between HA and CD44 can regulate the migration, proliferation, and differentiation of retinal progenitor cells, which is of great significance for future therapeutic applications.
STEM CELL REVIEWS AND REPORTS
(2023)
Article
Cell Biology
Moawiah M. Naffaa, Rehan R. Khan, Chay T. Kuo, Henry H. Yin
Summary: This study identifies a neural circuit that regulates neurogenesis and cell proliferation in the lateral ventricle-subventricular zone. Glutamatergic projections from the anterior cingulate cortex and inhibitory projections from local interneurons modulate the activity of cholinergic neurons in the subependymal zone. Optogenetic stimulation and inhibition of this circuit can control neurogenesis in the ventral SVZ.
Article
Biochemistry & Molecular Biology
Tong Zheng, Donna F. Bielinski, Derek R. Fisher, Jianyi Zhang, Barbara Shukitt-Hale
Summary: Blueberry extract has a positive effect on the viability and proliferation rates of adult hippocampal progenitor cells, potentially reversing decreases caused by dopamine, possibly due to its anti-inflammatory, antioxidant, and calcium-buffering properties.
Article
Neurosciences
Chikako Nakajima, Masato Sawada, Kazunobu Sawamoto
Summary: Postnatal neuronal migration plays a crucial role in regulating neuronal circuit formation and function throughout life, with pathological conditions activating neuroblast generation and migration towards lesions. Understanding the factors impeding neuronal migration is essential for functional brain recovery, highlighting the importance of modifying intrinsic capacity or improving the environment for successful migration to lesion sites.
CURRENT OPINION IN NEUROBIOLOGY
(2021)
Article
Cell Biology
Ming Jiang, Tianxiang Tang, Xinyue Liang, Juchen Li, Yue Qiu, Shiwen Liu, Shan Bian, Yunli Xie, Fang Fang, Jing Cang
Summary: Maternal exposure to sevoflurane temporarily disrupts INM of RGPs without altering cell fate, potentially through the Notch signalling pathway. Offspring show no obvious cognitive impairments in MWM. Abnormalities observed in hESC-derived cerebral organoids offer new insights into general anaesthesia effects on human brain development.
CELL PROLIFERATION
(2021)
Review
Neurosciences
Janne Hakanen, Nicolas Parmentier, Leonie Sommacal, Dario Garcia-Sanchez, Mohamed Aittaleb, Didier Vertommen, Libing Zhou, Nuria Ruiz-Reig, Fadel Tissir
Summary: The planar cell polarity protein Celsr3 and the microtubule depolymerizing protein Kif2a cooperatively specify the directionality of neuroblasts tangential migration in the postnatal brain, providing new insights into the mechanisms of neuroblast migration.
PROGRESS IN NEUROBIOLOGY
(2022)
Article
Neurosciences
Danielle de Paula Moreira, Angela May Suzuki, Andre Luiz Teles e Silva, Elisa Varella-Branco, Maria Cecilia Zorel Meneghetti, Gerson Shigeru Kobayashi, Mariana Fogo, Merari de Fatima Ramires Ferrari, Rafaela Regina Cardoso, Naila Cristina Vilaca Lourenco, Karina Griesi-Oliveira, Elaine Cristina Zachi, Debora Romeo Bertola, Karina de Souza Weinmann, Marcelo Andrade de Lima, Helena Bonciani Nader, Andrea Laurato Sertie, Maria Rita Passos-Bueno
Summary: Biallelic pathogenic variants in TBCK lead to IHPRF3, but the molecular mechanisms are not fully understood. This study reported two sisters with IHPRF3 and TBCK variants and provided evidence that TBCK may play a critical role in the early secretory pathway in neuroprogenitor cells. Impairment of TBCK function has been associated with disrupted vesicle transport and autophagosome biogenesis, altered cell cycle progression, and impaired migration capacity.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Multidisciplinary Sciences
Arpan Parichha, Varun Suresh, Mallika Chatterjee, Aditya Kshirsagar, Lihi Ben-Reuven, Tsviya Olender, M. Mark Taketo, Velena Radosevic, Mihaela Bobic-Rasonja, Sara Trnski, Michael J. Holtzman, Natasa Jovanov-Milosevic, Orly Reiner, Shubha Tole
Summary: The choroid plexus, responsible for secreting cerebrospinal fluid, plays a critical role in brain development and function. Activation of the Wnt signaling pathway is essential for the proper development of the choroid plexus, but over-activation of this pathway can lead to a loss of its properties and transformation into neurons.
NATURE COMMUNICATIONS
(2022)
Article
Clinical Neurology
Bruno Ghirotto, Danyllo F. Oliveira, Marcella Cipelli, Paulo J. Basso, Jean Lima, Cristiane N. S. Breda, Henrique C. Ribeiro, Camille C. C. Silva, Andrea L. Sertie, Antonio Edson R. Oliveira, Meire Hiyane, Elia G. Caldini, Alessandra Sussulini, Helder Nakaya, Alicia J. Kowaltowski, Enedina M. L. Oliveira, Mayana Zatz, Niels O. S. Camara
Summary: This study investigates the characteristics of astrocytes from patients with multiple sclerosis (MS) in terms of mitochondrial function and cell metabolism. The results show several differences in MS astrocytes, including enrichment of genes associated with neurodegeneration, increased mitochondrial fission, increased production of superoxide and proinflammatory chemokines, impaired glutamate uptake and enhanced release, increased electron transport capacity and proton leak, as well as a distinct metabolic profile. These findings provide new mechanistic insights into the metabolic rewiring of astrocytes in MS and suggest potential targets for future therapeutic studies.
ANNALS OF NEUROLOGY
(2022)
Article
Neurosciences
Ana Karolyne Santos Gomes, Rafaelly Mayara Dantas, Bruno Yukio Yokota, Andre Luiz Teles e Silva, Karina Griesi-Oliveira, Maria Rita Passos-Bueno, Andrea Laurato Sertie
Summary: Prenatal exposure to maternal immune activation (MIA) has been suggested to increase the probability of autism spectrum disorder (ASD). This study found that interleukin-17a (IL-17a) plays a key role in promoting brain abnormalities associated with ASD, and exogenous IL-17a positively regulates the neuronal differentiation of human neural progenitor cells (NPCs), potentially disrupting normal neuronal and synaptic development.
FRONTIERS IN NEUROSCIENCE
(2022)
Review
Cell Biology
Tamar Sapir, Dalit Sela-Donenfeld, Maayan Karlinski, Orly Reiner
Summary: This passage discusses the development and organization of the cortex from the caudal regions of the segmented neural tube, and suggests using a developmental perspective to understand common cortical malformations and their manifestation in the human brain.
Article
Cell Biology
E. Dominguez-Sala, L. Valdes-Sanchez, S. Canals, O. Reiner, A. Pombero, R. Garcia-Lopez, A. Estirado, D. Pastor, E. Geijo-Barrientos, S. Martinez
Summary: LIS1 (PAFAH1B1) plays a major role in the developing cerebral cortex and mutations in this gene can cause lissencephaly type 1. Research on mutant mice with a deletion in the first exon of the Lis1 gene revealed abnormal distribution and functional abnormalities in cortical GABAergic interneurons. Additionally, these mice exhibited altered oscillatory activity and abnormalities in the fast spiking inhibitory GABAergic interneurons. These findings suggest that certain mutations in the Lis1 gene can lead to phenotypes similar to those observed in patients with schizophrenia and autism.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Tamar Sapir, Aditya Kshirsagar, Anna Gorelik, Tsviya Olender, Ziv Porat, Ingrid E. Scheffer, David B. Goldstein, Orrin Devinsky, Orly Reiner
Summary: HNRNPU loss of function leads to rapid cell death of both postmitotic neurons and neural progenitors, with a higher sensitivity of the latter. The expression and alternative splicing of multiple genes involved in cell survival, cell motility, and synapse formation are affected following Hnrnpu's conditional truncation. Pharmaceutical and genetic agents have been identified to partially reverse the loss of cortical structures in Hnrnpu mutated embryonic brains.
NATURE COMMUNICATIONS
(2022)
Article
Psychiatry
Andre Luiz Teles e Silva, Talita Glaser, Karina Griesi-Oliveira, Juliana Correa-Velloso, Jaqueline Yu Ting Wang, Gabriele da Silva Campos, Henning Ulrich, Andrea Balan, Mehdi Zarrei, Edward J. Higginbotham, Stephen W. Scherer, Maria Rita Passos-Bueno, Andrea Laurato Sertie
Summary: This study reveals the neurobiological mechanisms underlying oligogenic ASD, showing that variants in specific genes lead to increased intracellular calcium influx, overactivation of the mTORC1 pathway, and further impairment in Reelin signaling. Additionally, the co-occurrence of risk variants in genes related to the Reelin pathway and calcium channels confers significant liability for ASD.
TRANSLATIONAL PSYCHIATRY
(2022)
Article
Multidisciplinary Sciences
Sergiu P. Pasca, Paola Arlotta, Helen S. Bateup, J. Gray Camp, Silvia Cappello, Fred H. Gage, Juergen A. Knoblich, Arnold R. Kriegstein, Madeline A. Lancaster, Guo-Li Ming, Alysson R. Muotri, In-Hyun Park, Orly Reiner, Hongjun Song, Lorenz Studer, Sally Temple, Giuseppe Testa, Barbara Treutlein, Flora M. Vaccarino
Summary: The nomenclature of human multicellular models of nervous system development and disease, including organoids, assembloids, and transplants, is clarified and provided as a basic framework to facilitate progress and improve communication with the scientific community and the public. These models derived from human pluripotent stem cells or primary tissue have the potential to provide insights into the unique development of the human nervous system and the progression and treatment of nervous system disorders.
Editorial Material
Neurosciences
Liang Qiang, Michael A. Lane, Claudia A. Doege, Orly Reiner, Itzhak Fischer
FRONTIERS IN CELLULAR NEUROSCIENCE
(2023)
Article
Multidisciplinary Sciences
Andrew K. Ressler, Gabriela L. A. Sampaio, Sarah A. Dugger, Tamar Sapir, Daniel Krizay, Michael J. Boland, Orly Reiner, David B. Goldstein
Summary: Generating effective therapies for neurodevelopmental disorders is challenging. An emerging approach is to characterize transcriptomic dysregulation in a model system and screen for therapeutics that restore functional expression patterns. We characterized dysregulation in a human model of HNRNPU-related disorder and compared it to mice models, finding enrichment of co-dysregulation between human organoids and embryonic mice. However, hnRNPU-deficient human organoids may only model transcriptional dysregulation in certain cell types during specific developmental periods.
Review
Biochemistry & Molecular Biology
Tamar Sapir, Orly Reiner
Summary: Heterogeneous nuclear ribonucleoprotein U (HNRNPU) is a nuclear protein that is involved in important biological functions such as RNA splicing and chromatin organization. Its activities, along with scaffold attachment factor A (SAF-A), are crucial for various processes including gene expression, DNA replication, genome integrity, and mitotic fidelity. HNRNPU is associated with neurodevelopmental disorders characterized by developmental delay and intellectual disability. Our research shows that the loss of HNRNPU function results in the death of neural progenitor cells and post-mitotic neurons, affecting gene expression and alternative splicing of genes involved in signaling pathways related to HNRNPU-related neurodevelopmental disorders.
Article
Medicine, Research & Experimental
Manuela Cassotta, Hugo Geerts, Lise Harbom, Tiago F. Outeiro, Iosif Pediaditakis, Orly Reiner, Stefan Schildknecht, Jens C. Schwamborn, Jarrod Bailey, Kathrin Herrmann, Helena T. Hogberg
Summary: Parkinson's disease (PD) is a complex neurodegenerative condition with a lack of preventive or curative therapies. New approach methodologies (NAMs) hold potential to advance PD research and reduce the reliance on animal-based studies. Key recommendations to advance PD research include integrating NAMs, learning from other neurodegenerative diseases, increasing data sharing, promoting innovative pilot studies, and accessing philanthropic funding.
ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION
(2022)
Meeting Abstract
Biophysics
Orly Reiner, Aditya Kshirsagar
BIOPHYSICAL JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Orly Reiner, Tamar Sapir, Arpan Parichha
Summary: Parkinson's disease pathology may manifest earlier in the gastrointestinal track, human induced pluripotent stem cells and organoids aid in disease research, future models should aim to be more complex.
MOLECULAR PSYCHIATRY
(2021)