Article
Cell Biology
Jin-Lan Huang, Fan Zhang, Min Su, Jiaxin Li, Wen Yi, Li-Xiang Hou, Si-Man Yang, Jin-Yuan Liu, Hao-An Zhang, Tengfei Ma, Deng-Pan Wu
Summary: The study found that MeCP2 plays a crucial role in age-related cognitive decline by regulating synaptic plasticity. MeCP2's modulation of synaptic plasticity may be associated with the CREB1 pathway, indicating it as a promising target for the treatment of age-related cognitive decline in neurodegenerative diseases.
Article
Multidisciplinary Sciences
Junqi Kuang, Ziwei Zhai, Pengli Li, Ruona Shi, Wenjing Guo, Yuxiang Yao, Jing Guo, Guoqing Zhao, Jiangpin He, Shuyang Xu, Chuman Wu, Shengyong Yu, Chunhua Zhou, Linlin Wu, Yue Qin, Baomei Cai, Wei Li, Zichao Wu, Xiaoxi Li, Shilong Chu, Tingting Yang, Bo Wang, Shangtao Cao, Dongwei Li, Xiaofei Zhang, Jiekai Chen, Jing Liu, Duanqing Pei
Summary: The transition from pluripotent to somatic states is controlled by SS18, which forms microscopic condensates in nuclei through a unique tyrosine-based mechanism. The N-terminal 70 amino acids of SS18 interact with the BAF complex, playing a crucial role in the transition process.
NATURE COMMUNICATIONS
(2021)
Article
Neurosciences
Javier Flores Gutierrez, Giulia Natali, Jacopo Giorgi, Elvira De Leonibus, Enrico Tongiorgi
Summary: This study explored the treatment effect of MTZ on Rett Syndrome (RTT) and found that a 30-day MTZ treatment significantly improved body weight, motor behavior, and the development of perineuronal nets in young Mecp2(+/-) mice. These results suggest that MTZ may be a potential drug for the treatment of RTT.
EXPERIMENTAL NEUROLOGY
(2022)
Article
Cell Biology
Rebekka Wittrahm, Mari Takalo, Mikael Marttinen, Teemu Kuulasmaa, Petra Makinen, Susanna Kemppainen, Henna Martiskainen, Tuomas Rauramaa, Ian Pike, Ville Leinonen, Teemu Natunen, Annakaisa Haapasalo, Mikko Hiltunen
Summary: The phosphorylation of MECP2 at the S423 site decreased in the early stages of Alzheimer's disease-related pathology in the human temporal cortex. Overexpression of wild type MECP2 enhanced pro-inflammatory response in microglial cells, while the phosphorylation-deficient MECP2-S423A variant further increased pro-inflammatory response. MECP2 may influence inflammatory response in microglia independently of S423 and S80 phosphorylation, while S423 phosphorylation might play a role in neuronal gene expression activation for neuroprotection under neuroinflammation-related stress.
Article
Biochemistry & Molecular Biology
Matteo Moschetta, Tiziana Ravasenga, Antonio De Fusco, Luca Maragliano, Davide Aprile, Marta Orlando, Silvio Sacchetti, Silvia Casagrande, Gabriele Lignani, Anna Fassio, Pietro Baldelli, Fabio Benfenati
Summary: The study reveals that Synapsin I acts as a novel Ca2+ buffer in excitatory terminals, and blocking its binding to Ca2+ leads to abnormal neurotransmitter release and short-term plasticity. This finding sheds light on the physiological role of Ca2+ binding to SynI in the regulation of SV clustering and trafficking in nerve terminals.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Multidisciplinary Sciences
Kouya Uchino, Yasuyoshi Tanaka, Sayaka Kawaguchi, Kaori Kubota, Takuya Watanabe, Shutaro Katsurabayashi, Shinichi Hirose, Katsunori Iwasaki
Summary: Researchers developed an autaptic culture system containing human iPSC-derived astrocytes to study the effects of astrocytes on synaptic functions. They found that compared to neuron monocultures, the cultures with human iPSC-derived astrocytes exhibited significantly higher Na+ current amplitude, membrane capacitance, number of synapses, and dendrite length.
Article
Multidisciplinary Sciences
Xianli Shen, Yiguo Qiu, Andrew E. Wight, Hye-Jung Kim, Harvey Cantor
Summary: Expression of CD11c and OPN marks a stable microglial subset in the brain, independent of environmental activation stimuli. OPN is required for subset stability and the execution of phagocytic and proinflammatory responses.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Kwong-Man Ng, Qianqian Ding, Yiu-Lam Tse, Oscar Hou-In Chou, Wing-Hon Lai, Ka-Wing Au, Yee-Man Lau, Yue Ji, Chung-Wah Siu, Clara Sze-Man Tang, Alan Colman, Suk-Ying Tsang, Hung-Fat Tse
Summary: This study investigated the pathophysiological roles of MeCP2 mutations in the etiology of intrinsic cardiac abnormality in Rett syndrome. The findings suggest that MeCP2 mutations lead to up-regulation of Wnt family genes, which in turn affect the electrophysiological properties of cardiac cells. These results provide novel insights into the contribution of the Wnt/beta-catenin signaling cascade to the cardiac abnormalities associated with MeCP2 mutations in RTT.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Hermany Munguba, Bidisha Chattopadhyaya, Stephan Nilsson, Josianne N. Carrico, Fatima Memic, Polina Oberst, Renata Batista-Brito, Ana Belen Munoz-Manchado, Michael Wegner, Gordon Fishell, Graziella Di Cristo, Jens Hjerling-Leffler
Summary: Pvalb(+) neurons provide robust inhibition to neighboring pyramidal neurons and undergo extensive synaptic formation and maturation during the first weeks after birth and continue to dynamically maintain their synaptic output throughout adulthood. Sox6 plays a crucial role in the postnatal maturation and synaptic function of cortical Pvalb(+) neurons, with its loss leading to synaptic bouton growth failure and shrinkage of established boutons. These findings suggest a constitutive role for Sox6 in maintaining synaptic output from Pvalb(+) neurons into adulthood.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Multidisciplinary Sciences
Lily Sarrafha, Drew R. Neavin, Gustavo M. Parfitt, Ilya A. Kruglikov, Kristen Whitney, Ricardo Reyes, Elena Coccia, Tatyana Kareva, Camille Goldman, Regine Tipon, Gist Croft, John F. Crary, Joseph E. Powell, Joel Blanchard, Tim Ahfeldt
Summary: In this study, a differentiation protocol for hypothalamus organoids derived from human pluripotent stem cells (hPSCs) was established to model the cellular diversity of this brain region. Using electrophysiologically active hypothalamus organoids, the specific pathways and functions of dopaminergic neurons (DNs) were investigated. Single-cell RNA sequencing (scRNA-seq) revealed diverse neuronal and non-neuronal cell types in mature hypothalamus organoids. This 3D hypothalamus differentiation protocol can be used to study the development of this critical brain structure and to model diseases centered around the hypothalamus.
Article
Neurosciences
Lingjie He, Matthew S. Caudill, Junzhan Jing, Wei Wang, Yaling Sun, Jianrong Tang, Xiaolong Jiang, Huda Y. Zoghbi
Summary: Successfully recalling a memory requires the reactivation of hippocampal cell ensembles. In the case of Rett syndrome (RTT), a neurological disorder, the balance of excitation-to-inhibition is altered, leading to difficulties in memory recall. Through in vivo imaging and multiple whole-cell recordings, it was found that RTT CA1 cells struggle to distinguish mnemonic context and form larger ensembles during long-term memory retrieval. Chemogenetic manipulation revealed that reduced activity of SOM inhibitory neurons underlies the poor long-term memory recall in RTT.
Article
Multidisciplinary Sciences
Marine Lacomme, Sarah C. Hales, Thomas W. Brown, Katarina Stevanovic, Christine Jolicoeur, Jenny Cai, Therence Bois, Melissa Desrosiers, Deniz Dalkara, Michel Cayouette
Summary: This study reveals Numb as a key regulator of intracellular Tau levels and identifies Numb-72 as a potential therapeutic factor for tauopathies.
Article
Cell Biology
Kenyi Saito-Diaz, Christina James, Archie Jayesh Patel, Nadja Zeltner
Summary: This study demonstrates the use of immunopanning method to isolate different subtypes of sensory neurons and successfully enriches the target subtypes with their respective subtype markers. It provides an effective method for further investigation of the development and diseases of sensory neurons.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Biology
Ni Li, Michael Edel, Kun Liu, Chris Denning, Jacob Betts, Oliver C. Neely, Dan Li, David J. Paterson
Summary: Human induced pluripotent stem cells (hiPSC) have the potential to generate model systems for studying human disease. Current protocols can generate cardiac myocytes (hiPSC-CM) and sympathetic neurons (hiPSC-SN). However, the ability of hiPSC-derived neurocardiac co-culture systems to mimic the human phenotype in disease modelling is still in early stages.
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2023)
Review
Cell & Tissue Engineering
Hang Zhou, Yun Wang, Li-Ping Liu, Yu-Mei Li, Yun-Wen Zheng
Summary: The rapid development of gene-editing technology has broadened the applications of pluripotent stem cells (PSCs) and their derived organoids in regenerative medicine. Despite ethical concerns and safety risks, PSC gene editing continues to benefit mankind at an unprecedented rate.
STEM CELLS INTERNATIONAL
(2021)
Article
Neurosciences
Avanti Gokhale, Cortnie Hartwig, Amanda A. H. Freeman, Julia L. Bassell, Stephanie A. Zlatic, Christie Sapp Savas, Trishna Vadlamudi, Farida Abudulai, Tyler T. Pham, Amanda Crocker, Erica Werner, Zhexing Wen, Gabriela M. Repetto, Joseph A. Gogos, Steven M. Claypool, Jennifer K. Forsyth, Carrie E. Bearden, Jill Glausier, David A. Lewis, Nicholas T. Seyfried, Jennifer Q. Kwong, Victor Faundez
JOURNAL OF NEUROSCIENCE
(2019)
Review
Neurosciences
Wei Li, Lucas Pozzo-Miller
JOURNAL OF NEUROSCIENCE RESEARCH
(2020)
Article
Clinical Neurology
Prativa Sherchan, Fayth Miles, Michael Orlich, Gary Fraser, John H. Zhang, Konrad Talbot, Penelope J. Duerksen-Hughes
TRANSLATIONAL STROKE RESEARCH
(2020)
Article
Neurosciences
Frank Y. Lee, Jennifer Larimore, Victor Faundez, Esteban C. Dell'Angelica, Cristina A. Ghiani
Summary: The absence of BLOC-1 during brain development affects male mice more than females, particularly in the hippocampus. While most abnormalities in juvenile animals seem to have been resolved, potential permanent defects may result in faulty neuronal circuits and contribute to cognitive and behavioral phenotypes in adult BLOC-1-deficient mice.
JOURNAL OF NEUROSCIENCE RESEARCH
(2021)
Editorial Material
Biochemistry & Molecular Biology
Gopal P. Sarma, Allan Levey, Victor Faundez
Article
Pharmacology & Pharmacy
Therese S. Salameh, Elizabeth M. Rhea, Konrad Talbot, William A. Banks
BIOCHEMICAL PHARMACOLOGY
(2020)
Article
Neurosciences
Pernille Bulow, Stephanie A. Zlatic, Peter A. Wenner, Gary J. Bassell, Victor Faundez
Summary: This study found an increased number of mitochondrial annotated proteins in the proteome of cortical neurons sensitive to both activity deprivation and Fmr1(-/y) genotype, suggesting a novel role of FMRP in attenuating mitochondrial proteome modifications induced by activity deprivation.
Article
Cell Biology
Jessica N. Peoples, Nasab Ghazal, Duc M. Duong, Katherine R. Hardin, Janet R. Manning, Nicholas T. Seyfried, Victor Faundez, Jennifer Q. Kwong
Summary: Mitochondria can trigger various signaling pathways under stress conditions, with mitochondrial energy dysfunction leading to a pattern of acylome remodeling. This remodeling specifically impacts mitochondrial proteins, with acetylation and malonylation modifying the interactome and enzyme activity within mitochondria. Additionally, a novel cross talk between acetylation and malonylation was discovered, indicating a mechanism by which disruption to energy production can impact global mitochondrial function.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2021)
Editorial Material
Cell Biology
Kaela S. Singleton, Victor Faundez
Summary: In this study, Bowman et al. illustrate a novel mechanism where AP-3 and BLOC-1 complexes, together with syntaxin 13, act as a fail-safe system to recognize sorting signals in VAMP7, ensuring its loading into nascent carriers. This observation represents one of the first instances of distributed robustness in membrane traffic mechanisms.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Neurosciences
Meghan E. Wynne, Alicia R. Lane, Kaela S. Singleton, Stephanie A. Zlatic, Avanti Gokhale, Erica Werner, Duc Duong, Jennifer Q. Kwong, Amanda J. Crocker, Victor Faundez
Summary: The mitochondrial composition varies among brain regions and neuronal cell types, as shown in a study on mice. Single-cell mitochondrial transcriptomes can distinguish different types of neurons, indicating that mitochondrial heterogeneity may influence specific mechanisms in health and disease.
Article
Multidisciplinary Sciences
Thomas S. Wingo, Yue Liu, Ekaterina S. Gerasimov, Selina M. Vattathil, Meghan E. Wynne, Jiaqi Liu, Adriana Lori, Victor Faundez, David A. Bennett, Nicholas T. Seyfried, Allan Levey, Aliza P. Wingo
Summary: The study finds evidence for shared genetic and molecular pathophysiology between several common psychiatric and neurodegenerative diseases, which has important implications for early treatment and therapeutic development.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Pernille Bulow, Anupam Patgiri, Victor Faundez
Summary: The human brain consumes a significantly larger amount of energy than the sun by unit of mass and time. Defects in the machinery for cellular energy production, particularly in mitochondrial protein synthesis, may be a causative mechanism for neurodevelopmental and behavioral disorders.
Article
Cell Biology
E. Werner, A. Gokhale, M. Ackert, C. Xu, Z. Wen, A. M. Roberts, B. R. Roberts, A. Vrailas-Mortimer, A. Crocker, V Faundez
Summary: By studying genetic cellular models, we found that manganese exposure compromises the function and composition of mitochondrial RNA granules, leading to disruption of mitochondrial transcript processing and respiratory chain function. Interestingly, impaired RNA granule function acts as a protective mechanism against acute manganese toxicity.
MOLECULAR BIOLOGY OF THE CELL
(2022)
Article
Multidisciplinary Sciences
Stephanie A. Zlatic, Duc Duong, Kamal K. E. Gadalla, Brenda Murage, Lingyan Ping, Ruth Shah, James J. Fink, Omar Khwaja, Lindsay C. Swanson, Mustafa Sahin, Sruti Rayaprolu, Prateek Kumar, Srikant Rangaraju, Adrian Bird, Daniel Tarquinio, Randall Carpenter, Stuart Cobb, Victor Faundez
Summary: This study investigates the proteome of Rett cerebrospinal fluid (CSF) and identifies proteins associated with HDL lipoproteins, complement, mitochondria, citrate/pyruvate metabolism, synapse compartments, and the neurosecretory protein VGF. The differentially expressed CSF proteins can distinguish Rett syndrome from a related neurodevelopmental disorder. These findings provide insights into potential mechanisms and biomarkers of Rett syndrome.
Article
Biology
Meghan E. Wynne, Oluwaseun Ogunbona, Alicia R. Lane, Avanti Gokhale, Stephanie A. Zlatic, Chongchong Xu, Zhexing Wen, Duc M. Duong, Sruti Rayaprolu, Anna Ivanova, Eric A. Ortlund, Eric B. Dammer, Nicholas T. Seyfried, Blaine R. Roberts, Amanda Crocker, Vinit Shanbhag, Michael Petris, Nanami Senoo, Selvaraju Kandasamy, Steven Michael Claypool, Antoni Barrientos, Aliza Wingo, Thomas S. Wingo, Srikant Rangaraju, Allan I. Levey, Erica Werner, Victor Faundez
Summary: This study demonstrates that mitochondria play a role in regulating the secretome, specifically the upregulation of APOE and other secretome components. Disruption of the electron transport chain, either genetically or pharmacologically, leads to the upregulation of APOE transcript, protein, and secretion. These findings suggest that mitochondria act as upstream regulators of APOE-dependent processes and may play a role in neurodegeneration and Alzheimer's disease.