Review
Clinical Neurology
Babak Arjmand, Shayesteh Kokabi Hamidpour, Zahra Rabbani, Akram Tayanloo-Beik, Fakher Rahim, Hamid Reza Aghayan, Bagher Larijani
Summary: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that causes motor neuron degeneration, leading to mobility impairments. Current treatments only provide symptomatic relief, highlighting the need for novel therapies. However, the process of discovering new drugs for ALS is challenging, and a comprehensive understanding of the disease process is lacking. Increased application of regenerative medicine, especially tissue engineering and stem cell therapy, could lead to the development of more novel technologies, such as organ-on-a-chip, which can mimic ALS complexities and serve as a cost-effective disease modeling platform.
FRONTIERS IN NEUROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Maria G. Otero, Shaughn Bell, Alexander H. Laperle, George Lawless, Zachary Myers, Marian A. Castro, Jaquelyn M. Villalba, Clive N. Svendsen
Summary: Conventional tissue culture platforms limit the study of cell biology due to lack of maturity, while organ-chip microfluidic systems provide a more physiological environment for cell growth. In this study, organ-chip cultures showed a higher proportion and homogeneity of mature dopamine neurons compared to multi-well cultures. These organ-chips are ideal for studying the biology of mature dopamine neurons in health and neurological disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Albin A. Bernardin, Sarah Colombani, Antoine Rousselot, Virginie Andry, Yannick Goumon, Helene Delanoe-Ayari, Come Pasqualin, Bernard Brugg, Etienne D. Jacotot, Jean-Luc Pasquie, Alain Lacampagne, Albano C. Meli
Summary: This study presents an innovative neuro-cardiac organ-on-chip model to study the neuro-cardiac junction (NCJ) and understand the mechanisms involved in its establishment. The model successfully recapitulates the structural and functional properties of the NCJ and allows for the evaluation of the interaction between the heart and brain, as well as the impact of drugs on a reconstructed human neuro-cardiac system.
Review
Medicine, General & Internal
Job Komen, Sanne M. van Neerven, Albert van den Berg, Louis Vermeulen, Andries D. van der Meer
Summary: This study explores the potential of using organ-on-chip technology to mimic cancer xenograft models for validating cancer-on-chip models. By reviewing the biological characteristics and comparing the growth of on-chip tumors with xenografts, it shows that organ-on-chip technology is capable of mimicking many aspects of xenograft tumors, yet further development and validation is needed.
Article
Biochemistry & Molecular Biology
Robin Waegaert, Sylvie Dirrig-Grosch, Haoyi Liu, Marion Boutry, Ping Luan, Jean-Philippe Loeffler, Frederique Rene
Summary: CHMP2B is a crucial protein involved in membrane scission events and its mutations are a rare cause of ALS and FTD. This study demonstrates that neuron-specific expression of the CHMP2B(intron5) mutant leads to progressive gait impairment and changes in the neuromuscular junction, similar to those observed in ALS patients.
Review
Chemistry, Multidisciplinary
Yubing Leng, Xiaorui Li, Fuyin Zheng, Hui Liu, Chunyan Wang, Xudong Wang, Yulong Liao, Jiangyue Liu, Kaiqi Meng, Jiaheng Yu, Jingyi Zhang, Binyu Wang, Yingjun Tan, Meili Liu, Xiaoling Jia, Deyu Li, Yinghui Li, Zhongze Gu, Yubo Fan
Summary: The neuromuscular junction (NMJ) is a peripheral synaptic connection that enables muscle contraction and voluntary motor movement. Recent advances in in vitro NMJ models have allowed for better understanding, control, and evaluation of its functions, using techniques such as organ-on-a-chip and biohybrid robotics. Functional analysis methods including the patch-clamp technique, microelectrode arrays, calcium imaging, and various stimulus methods have also been developed. These models have potential applications in disease modeling and drug screening for neuromuscular diseases.
ADVANCED MATERIALS
(2023)
Article
Cell Biology
Baofeng Feng, Asiamah Ernest Amponsah, Ruiyun Guo, Xin Liu, Jinyu Zhang, Xiaofeng Du, Zijing Zhou, Jingjing He, Jun Ma, Huixian Cui
Summary: The study suggests that aberrant cytokine secretion by astrocytes derived from induced pluripotent stem cells (iPSCs) of amyotrophic lateral sclerosis (ALS) patients is regulated by the mTOR-autophagy pathway. Activating autophagy could reduce cytokine secretion by ALS astrocytes, potentially mitigating their toxic effects on motor neurons.
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
(2022)
Article
Multidisciplinary Sciences
Marina Boido, Iacopo Gesmundo, Anna Caretto, Francesca Pedrolli, Roberta Schellino, Sheila Leone, Renzhi Cai, Wei Sha, Ezio Ghigo, Andrew V. Schally, Alessandro Vercelli, Riccarda Granata
Summary: The study shows that MR-409 has protective effects on SMN Delta 7 mice, indicating its potential as a promising drug for the treatment of SMA.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biophysics
Shan Liu, Shikha Kumari, Hongyi He, Parichita Mishra, Bhisham Narayan Singh, Divakar Singh, Sutong Liu, Pradeep Srivastava, Chenzhong Li
Summary: As a simulation of human cells, tissues, organs, and systems, Organ-on-a-Chip (OOC) has ethical advantages and development potential over animal experiments. Advancements in 3D cell biology and engineering, chip materials, and 3D printing have facilitated the connection of multi-organs-on-chips for simulation and the development of new drug screening platforms. The success of organ model modeling is crucial, and this paper provides a comprehensive review and discussion of detection and evaluation technologies in organ-on-a-chip research.
BIOSENSORS & BIOELECTRONICS
(2023)
Review
Health Care Sciences & Services
Ekene Anakor, William John Duddy, Stephanie Duguez
Summary: Amyotrophic lateral sclerosis is a disease that affects the upper and lower motor neurons. It has been found that the disease not only affects motor neurons, but also other tissues and cell types, leading to metabolic dysfunctions, impaired proteostasis, deficits in muscle regeneration and RNA metabolism. Skeletal muscle is considered an important contributor to the occurrence and progression of the disease, acting as a secretory organ and affecting the skeletal muscle secretome, which can have consequences for neuronal function and survival.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Review
Pharmacology & Pharmacy
Jingyu Fu, Hailong Qiu, Cherie S. Tan
Summary: Drug discovery is a costly and complex process, and efficient methods are needed to screen potential compounds and remove toxic substances. The liver plays a crucial role in determining drug efficacy and potential side effects. The liver-on-a-chip platform based on microfluidic technology has gained attention for its ability to predict drug metabolism and hepatotoxicity, as well as study pharmacokinetics and pharmacodynamics when combined with other organ-on-chip systems.
Article
Engineering, Biomedical
Cathleen Hagemann, Carmen Moreno Gonzalez, Ludovica Guetta, Giulia Tyzack, Ciro Chiappini, Andrea Legati, Rickie Patani, Andrea Serio
Summary: Stem cell-based experimental platforms in neuroscience can effectively mimic key aspects of human development and disease. However, conventional culture systems may not accurately represent the engineering constraints faced by cells in vivo, especially for neurons with long axons like spinal motor neurons. The establishment of a bioengineered platform to assemble arrays of human axons of various lengths has revealed a link between axon length and metabolism in human motor neurons, shedding light on a length-dependent mechanism that influences homeostatic processes within these cells. These findings have important implications for modeling neurodegenerative disorders in vitro and emphasize the importance of accurately modeling cell shape and biophysical constraints in experimental settings.
ADVANCED HEALTHCARE MATERIALS
(2022)
Review
Nanoscience & Nanotechnology
Daniel Vera, Maria Garcia-Diaz, Nuria Torras, Mar Alvarez, Rosa Villa, Elena Martinez
Summary: Researchers have integrated hydrogels into microfluidic setups to develop tissue barrier-on-chips that accurately account for different cellular and acellular compartments, including the cellular components and functionality of in vivo tissues. These platforms have the potential to greatly improve the predictive capacities of in vitro systems in applications such as drug development or disease modeling, but face challenges in microfabrication.
ACS APPLIED MATERIALS & INTERFACES
(2021)
Article
Biochemistry & Molecular Biology
Cristina Pinto, Viviana Perez, Jessica Mella, Miguel Albistur, Teresa Caprile, Francisca C. Bronfman, Juan Pablo Henriquez
Summary: The study demonstrates that Wnt3 is transported and secreted by motor neurons to induce postsynaptic differentiation in nascent NMJs. Overexpression of Wnt3 in NSC-34 cells effectively induces acetylcholine receptor clustering on co-cultured myotubes.
Article
Cell Biology
Domiziana Costamagna, Valerie Casters, Marc Beltra, Maurilio Sampaolesi, Anja Van Campenhout, Els Ortibus, Kaat Desloovere, Robin Duelen
Summary: This study generated in vitro human neuromuscular junctions (NMJs) using a microfluidic strategy from patient-specific induced pluripotent stem cell (hiPSC) lines to model disease-relevant neuropathologic processes in hereditary spastic paraplegia (HSP). The unique strength of this NMJ model is its ability to generate lower motor neurons (MNs) and myotubes from autologous hiPSC origin while maintaining the genetic background of HSP patient donors. The study found that HSP-derived lines exhibited axonal swellings, reduced levels of SPASTIN protein, and impaired NMJ profiles, offering unique tools to study the pathologic mechanisms of HSP.
Article
Neurosciences
Ronja Markworth, Youri Adolfs, Vivian Dambeck, Lars M. Steinbeck, Muriel Lize, R. Jeroen Pasterkamp, Mathias Baehr, Camin Dean, Katja Burk
JOURNAL OF NEUROSCIENCE
(2019)
Article
Biology
Bin Wu, Francois G. C. Blot, Aaron Benson Wong, Catarina Osorio, Youri Adolfs, R. Jeroen Pasterkamp, Jana Hartmann, Esther B. E. Becker, Henk-Jan Boele, Chris De Zeeuw, Martijn Schonewille
Article
Biochemistry & Molecular Biology
Daniel Rozbesky, Marieke G. Verhagen, Dimple Karia, Gergely N. Nagy, Luis Alvarez, Ross A. Robinson, Karl Harlos, Sergi Padilla-Parra, R. Jeroen Pasterkamp, Edith Yvonne Jones
Review
Biochemistry & Molecular Biology
Vamshidhar R. Vangoor, Andreia Gomes-Duarte, R. Jeroen Pasterkamp
Summary: Long non-coding RNAs play crucial roles in the expression and development of motor neurons in the nervous system, and disruptions in their effects may contribute to motor neuron diseases. Research on the expression and functions of lncRNAs in motor neurons is shedding light on potential therapeutic targets for various motor neuron diseases.
JOURNAL OF NEUROCHEMISTRY
(2021)
Article
Neurosciences
Ruediger Klein, Ronald Jeroen Pasterkamp
CURRENT OPINION IN NEUROBIOLOGY
(2021)
Article
Neurosciences
Ramin Raoof, Christian Martin Gil, Floris P. J. G. Lafeber, Huub de Visser, Judith Prado, Sabine Versteeg, Mirte N. Pascha, Anne L. P. Heinemans, Youri Adolfs, Jeroen Pasterkamp, John N. Wood, Simon C. Mastbergen, Niels Eijkelkamp
Summary: This study reveals the crucial role of macrophages in maintaining OA pain independently from joint damage. Sensory neurons innervate damaged knee joints, shaping DRG macrophages into an M1 phenotype. Inhibiting M1-like macrophages in the DRG can resolve persistent OA pain.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Multidisciplinary Sciences
Valeria Bonapersona, Heike Schuler, Ruth Damsteegt, Youri Adolfs, R. Jeroen Pasterkamp, Martijn P. van den Heuvel, Marian Joels, R. Angela Sarabdjitsingh
Summary: Acute stress leads to sequential activation of functional brain networks, resulting in changes in cellular activity. The study found that areas such as the hypothalamus, amygdala, prefrontal cortex, hippocampus, and thalamus are most affected by acute stress. The cellular activity patterns also shift over time, and the strategy of some brain areas changes after stress.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
News Item
Clinical Neurology
Elly M. Hol, R. Jeroen Pasterkamp
Summary: The study combined genome-wide association data with microglial transcriptomes to identify functional variants underlying brain disorders. This information will contribute to further mechanistic studies into disease-associated microglial changes.
NATURE REVIEWS NEUROLOGY
(2022)
Correction
Clinical Neurology
Elly M. Hol, R. Jeroen Pasterkamp
NATURE REVIEWS NEUROLOGY
(2022)
Article
Multidisciplinary Sciences
Vanessa Donega, Astrid T. van der Geest, Jacqueline A. Sluijs, Roland E. van Dijk, Chi Chiu Wang, Onur Basak, R. Jeroen Pasterkamp, Elly M. Hol
Summary: This study identifies CD271(+) progenitors from the aged subventricular zone (SVZ) as late oligodendrocyte progenitor cells and suggests SFRP1 as a potential signal for maintaining quiescence of progenitors from the aged SVZ. Furthermore, the administration of WAY-316606, an SFRP1 inhibitor, stimulates activation of neural stem cells both in vitro and in vivo.
NATURE COMMUNICATIONS
(2022)
Article
Nutrition & Dietetics
Amber Berdenis van Berlekom, Raphael Kubler, Jeske W. Hoogeboom, Danielle Vonk, Jacqueline A. Sluijs, R. Jeroen Pasterkamp, Jinte Middeldorp, Aletta D. Kraneveld, Johan Garssen, Rene S. Kahn, Elly M. Hol, Lot D. de Witte, Marco P. Boks
Summary: There is compelling evidence that nutrition has a significant impact on human brain development. Previous studies have shown that three specific amino acids, histidine, lysine, and threonine, can synergistically inhibit mTOR activity and behavior. In this pioneering study, human cerebral organoids were used to investigate the impact of amino acid supplementation on neurodevelopment. The results showed that exposure to threonine, histidine, and lysine led to decreased mTOR activity, reduced organoid size, and altered gene expression, supporting findings from previous rodent studies.
Article
Neurosciences
Marloes Verkerke, Amber Berdenis van Berlekom, Vanessa Donega, Danielle Vonk, Jacqueline A. Sluijs, Nayab F. Butt, Lois Kistemaker, Lot D. de Witte, R. Jeroen Pasterkamp, Jinte Middeldorp, Elly M. Hol
Summary: This study investigates the development and maturation of astrocytes in cerebral organoids derived from human induced pluripotent stem cells. Based on morphological and transcriptomic analysis, it is found that the optimal time to study matured astrocytes is after 19 weeks in culture.
Article
Multidisciplinary Sciences
Francois G. C. Blot, Joshua J. White, Amy van Hattem, Licia Scotti, Vaishnavi Balaji, Youri Adolfs, R. Jeroen Pasterkamp, Chris I. De Zeeuw, Martijn Schonewille
Summary: The classification of neuronal subpopulations has advanced, but its impact on behavior is uncertain. The flocculus of the cerebellum is a suitable model for studying neuronal subpopulations. Through genetic targeting, the study demonstrates separate micromodules within the flocculus that involve distinct subpopulations of Purkinje cells. Furthermore, optogenetic excitation of these subpopulations produces movements with different kinematic profiles. These findings highlight the importance of subpopulations in mediating specific aspects of cerebellar behavior.
NATURE COMMUNICATIONS
(2023)
Correction
Multidisciplinary Sciences
Francois G. C. Blot, Joshua J. White, Amy van Hattem, Licia Scotti, Vaishnavi Balaji, Youri Adolfs, R. Jeroen Pasterkamp, Chris I. De Zeeuw, Martijn Schonewille
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Pei-Yang Gao, Ya-Nan Ou, Yi-Ming Huang, Zhi-Bo Wang, Yan Fu, Ya-Hui Ma, Qiong-Yao Li, Li-Yun Ma, Rui-Ping Cui, Yin-Chu Mi, Lan Tan, Jin-Tai Yu
Summary: Liver function may play a role in the progression of Alzheimer's disease. The study found that as AD progressed, certain liver function markers increased while others decreased. The relationship between liver function and CSF AD biomarkers indicates a potential mediation effect on cognition.
JOURNAL OF NEUROCHEMISTRY
(2024)