Article
Clinical Neurology
Dana Marafi, Jawid M. Fatih, Rauan Kaiyrzhanov, Matteo P. Ferla, Charul Gijavanekar, Aljazi Al-Maraghi, Ning Liu, Emily Sites, Hessa S. Alsaif, Mohammad Al-Owain, Mohamed Zakkariah, Ehab El-Anany, Ulviyya Guliyeva, Sughra Guliyeva, Colette Gaba, Ateeq Haseeb, Amal M. Alhashem, Enam Danish, Vasiliki Karageorgou, Christian Beetz, Alaa A. Subhi, Sureni Mullegama, Erin Torti, Monisha Sebastin, Margo Sheck Breilyn, Susan Duberstein, Mohamed S. Abdel-Hamid, Tadahiro Mitani, Haowei Du, Jill A. Rosenfeld, Shalini N. Jhangiani, Zeynep Coban Akdemir, Richard A. Gibbs, Jenny C. Taylor, Khalid A. Fakhro, Jill Hunter, Davut Pehlivan, Maha S. Zaki, Joseph G. Gleeson, Reza Maroofian, Henry Houlden, Jennifer E. Posey, V. Reid Sutton, Fowzan S. Alkuraya, Sarah H. Elsea, James R. Lupski
Summary: SLC38A3 is a novel disease gene for developmental and epileptic encephalopathy, and the likely pathophysiology of the disease is perturbations in glutamine homeostasis.
Article
Pharmacology & Pharmacy
Chuqiao Pan, Shijie Mao, Zeping Xiong, Zhao Chen, Ning Xu
Summary: Glutamate dehydrogenase (GDH) is a key enzyme in mammalian glutamate metabolism, participating in multiple metabolic pathways and cellular activities. Its dysfunction may lead to various neurodegenerative diseases. Activators and gene therapy targeting GDH have shown potential in protecting neurons and improving motor disorders caused by glutamate metabolism disorders. This approach offers new insights and treatment strategies for neurodegenerative diseases.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Corinne S. Wilson, Preeti Dohare, Shaina Orbeta, Julia W. Nalwalk, Yunfei Huang, Russell J. Ferland, Rajan Sah, Annalisa Scimemi, Alexander A. Mongin
Summary: The knockout of the LRRC8A gene in mice leads to seizures in adolescence, as well as abnormalities in neurons and astrocytes in the brain. These abnormalities are associated with reactive astrogliosis, as well as dysregulation of amino acid neurotransmitter uptake and supply by astrocytes.
Article
Clinical Neurology
Maxwell G. Farina, Mani Ratnesh S. Sandhu, Maxime Parent, Basavaraju G. Sanganahalli, Matthew Derbin, Roni Dhaher, Helen Wang, Hitten P. Zaveri, Yun Zhou, Niels C. Danbolt, Fahmeed Hyder, Tore Eid
Summary: The study successfully developed a method to precisely and specifically delete the GS gene in the postnatal brain, resulting in lower seizure thresholds, spontaneous recurrent seizures, and reduced functional connectivity.
Article
Biochemistry & Molecular Biology
Laura Mikel Mcnair, Jens Velde Andersen, Helle Sonderby Waagepetersen
Summary: This study reveals fundamental alterations in cellular energy and neurotransmitter metabolism in the aging brain, which may contribute to age-related hippocampal deficits.
NEUROCHEMISTRY INTERNATIONAL
(2023)
Article
Medicine, General & Internal
In-Hee Lee, Douglas I. Walker, Yufei Lin, Matthew Ryan Smith, Kenneth D. Mandl, Dean P. Jones, Sek Won Kong
Summary: This study found an association between plasma glutamine levels and clinical phenotypes in individuals with autism spectrum disorder (ASD), suggesting that plasma glutamine levels could serve as an endophenotype linking genetic risk and symptom severity. These findings may contribute to the development of novel therapeutic targets, selection of specific cohorts for clinical trials, and identification of target symptoms for future ASD treatment strategies.
Article
Anesthesiology
Qin-qin He, Man Yang, Jing Huang, Wei Wu, Kuo Tang, Yong Zhang, Jian Zhou, Wei Ou, Maodi Xie, Yu Liang, Peilin Lu, Yunxia Zuo, Hai Yu, Tao Li
Summary: Intermittent hypoxia exposure decreased mouse sensitivity to sevoflurane anesthesia through enhanced O-GlcNAc-dependent modulation of the glutamate-glutamine cycle in the brain, as shown by the experimental results.
BRITISH JOURNAL OF ANAESTHESIA
(2022)
Article
Neurosciences
Rachel Naomi Curry, Isamu Aiba, Jochen Meyer, Brittney Lozzi, Yeunjung Ko, Malcolm Ford McDonald, Anna Rosenbaum, Alexis Cervantes, Emmet Huang-Hobbs, Carolina Cocito, Jeffrey Peter Greenfield, Ali Jalali, Jay Gavvala, Carrie Mohila, Akdes Serin Harmanci, Jeffrey Noebels, Ganesh Rao, Benjamin Deneen
Summary: Seizures are a common feature of malignant glioma and recent studies have found that peritumoral synaptic dysregulation plays a role in brain hyperactivity and tumor progression. Through single-cell RNA sequencing and patient ECoG recordings, this study shows that seizure patients have enriched gene signatures related to synapse formation in their tumors. The gene IGSF3 is identified as a mediator of glioma progression and dysregulated neural circuitry, leading to spreading depolarization. Further investigation reveals that IGSF3 interacts with Kir4.1 to suppress potassium buffering and seizure patients have reduced expression of potassium handlers in proliferating tumor cells. In vivo imaging confirms that dysregulated synaptic activity originates from the tumor-neuron interface, validating findings in patients. This study highlights the importance of ion dyshomeostasis in tumor progression and seizures.
Article
Biochemistry & Molecular Biology
Duk-Shin Lee, Ji-Eun Kim
Summary: This study found that P2X7 receptor plays an important role in LPS-induced neuroinflammation by affecting Nrf2 activity/expression and GSH synthesis.
Review
Biochemistry & Molecular Biology
Jens Andersen, Arne Schousboe
Summary: Glutamine plays an essential role in cerebral metabolism, including ammonia homeostasis, energy metabolism, and neurotransmitter recycling. The balance of cerebral glutamine is regulated by the metabolic coupling of neurons and astrocytes, and disruptions in this balance are associated with various neurological diseases. Decreased astrocyte glutamine synthesis can lead to a deficiency in metabolic substrates and precursors for neurotransmitter synthesis in neurons, resulting in synaptic dysfunction.
NEUROCHEMICAL RESEARCH
(2023)
Article
Neurosciences
Jens Andersen, Sofie K. Christensen, Emil W. Westi, Marta Diaz-delCastillo, Heikki Tanila, Arne Schousboe, Blanca Aldana, Helle S. Waagepetersen
Summary: This study found that in Alzheimer's disease (AD), there is prominent neuronal hypometabolism in the hippocampal slices of affected mice, while a reduction in glutamine synthesis in astrocytes directly impedes neuronal GABA synthesis.
NEUROBIOLOGY OF DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Veronica Rodriguez-Herrero, Arnau Peris, Monica Camacho, Vanesa Bautista, Julia Esclapez, Maria-Jose Bonete
Summary: The study uncovers a new metabolic pathway in halophilic archaea, expanding the understanding of alternative nitrogen source utilization in this domain.
Article
Multidisciplinary Sciences
Marinus Toman, John Joseph Wade, Alexei Verkhratsky, Mark Dallas, Angela Bithell, Bronac Flanagan, Jim Harkin, Liam McDaid
Summary: In this study, a computational model is used to investigate the impact of the spatial relationship between astrocytes and synapses on ionic homeostasis. The results show that the degree of astrocyte coverage affects the concentrations of K+, Na+, and Ca2+, particularly the uptake of Ca2+. Moreover, the proximity of astrocytic leaflets to the synaptic cleft determines the formation of Ca2+ microdomains, which may affect leaflet motility.
SCIENTIFIC REPORTS
(2023)
Article
Biochemistry & Molecular Biology
Suting Liu, Hao Cheng, Liying Cui, Li Jin, Yunzi Li, Chao Zhu, Qing Ji, Jun Tang
Summary: Activation of astrocytes and changes in the levels of astrocytic glutamate transporter-1 (GLT-1) play critical roles in neuropathic pain development. P2Y1 purinergic receptor (P2Y1R) contributes to pain transduction by regulating glutamate release and synaptic transmission. In a rat model of spinal nerve ligation (SNL), up-regulated expression of P2Y1R and activation of A1 astrocytes were observed, while astrocyte-specific knockdown of P2Y1R alleviated SNL-induced nociceptive responses and enhanced GLT-1 expression.
JOURNAL OF NEUROCHEMISTRY
(2023)
Review
Cell Biology
Veronica Marabitti, Manuela Giansanti, Francesca De Mitri, Francesca Gatto, Angela Mastronuzzi, Francesca Nazio
Summary: Tumor-specific alterations in metabolism are crucial for sustaining cell growth and survival in various cancers, but the heterogeneous nature of metabolism poses challenges for effective anticancer therapies. Medulloblastoma is a highly heterogeneous pediatric brain tumor with complex intratumoral cellular diversity. This review highlights the mechanisms through which medulloblastoma cells rewire their metabolism and energy production networks to support rapid growth, resistance to stress, invasion, metastasis, and therapy. The potential clinical benefits of targeting energy metabolism in suppressing medulloblastoma progression and enhancing current therapies are also discussed.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Themasap A. Khan, Omer Revah, Aaron Gordon, Se-Jin Yoon, Anna K. Krawisz, Carleton Goold, Yishan Sun, Chul Hoon Kim, Yuan Tian, Min-Yin Li, Julia M. Schaepe, Kazuya Ikeda, Neal D. Amin, Noriaki Sakai, Masayuki Yazawa, Leila Kushan, Seiji Nishino, Matthew H. Porteus, Judith L. Rapoport, Jonathan A. Bernstein, Ruth O'Hara, Carrie E. Bearden, Joachim F. Hallmayer, John R. Huguenard, Daniel H. Geschwind, Ricardo E. Dolmetsch, Sergiu P. Pasca
Editorial Material
Clinical Neurology
John R. Huguenard
Article
Biology
Adam C. Lu, Christine Kyuyoung Lee, Max Kleiman-Weiner, Brian Truong, Megan Wang, John R. Huguenard, Mark P. Beenhakker
Article
Multidisciplinary Sciences
Anna K. Koster, Austin L. Reese, Yuri Kuryshev, Xianlan Wen, Keri A. McKiernan, Erin E. Gray, Caiyun Wu, John R. Huguenard, Merritt Maduke, J. Du Bois
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Neurosciences
Aaron Gordon, Se-Jin Yoon, Stephen S. Tran, Christopher D. Makinson, Jin Young Park, Jimena Andersen, Alfredo M. Valencia, Steve Horvath, Xinshu Xiao, John R. Huguenard, Sergiu P. Pasca, Daniel H. Geschwind
Summary: Research shows that three-dimensional human cortical organoids can reach stages of postnatal brain development after being cultured for 250 to 300 days, paralleling in vivo development. These findings provide important insights and tools for modeling neurodevelopmental diseases.
NATURE NEUROSCIENCE
(2021)
Article
Genetics & Heredity
Astra S. Bryant, Elissa A. Hallem
Summary: Advances in genomics techniques have made it possible to expand the range of nematode species suitable for transgenesis, with codon optimization being a critical step for successful expression of exogenous transgenes. A new tool called Wild Worm Codon Adapter has been developed to rapidly optimize transgene codons for non-Caenorhabditis nematodes, including parasitic and predatory nematodes, with the option for custom optimization and automated intron insertion. This web-based tool also allows for the analysis of codon bias in transgenes and native sequences, as demonstrated in the analysis of Strongyloides species' genome-wide codon bias.
G3-GENES GENOMES GENETICS
(2021)
Article
Multidisciplinary Sciences
Yuan Pan, Jared D. Hysinger, Tara Barron, Nicki F. Schindler, Olivia Cobb, Xiaofan Guo, Belgin Yalcin, Corina Anastasaki, Sara B. Mulinyawe, Anitha Ponnuswami, Suzanne Scheaffer, Yu Ma, Kun-Che Chang, Xin Xia, Joseph A. Toonen, James J. Lennon, Erin M. Gibson, John R. Huguenard, Linda M. Liau, Jeffrey L. Goldberg, Michelle Monje, David H. Gutmann
Summary: Neurons play an essential role in promoting the growth of certain types of brain tumors, such as optic pathway gliomas driven by mutations in the NF1 tumor suppressor gene. Inhibition of neuronal activity through light deprivation can prevent tumor formation and progression, highlighting a potential therapeutic strategy and the importance of Nf1 mutation-mediated dysregulation of neuronal signaling pathways in cancer predisposition syndromes.
Article
Multidisciplinary Sciences
Anna Elleman, Gabrielle Devienne, Christopher D. Makinson, Allison L. Haynes, John R. Huguenard, J. Du Bois
Summary: The researchers have found that a synthetic saxitoxin derivative affixed to a photocleavable protecting group can control Na channels and have a precise impact on neurons.
NATURE COMMUNICATIONS
(2021)
Article
Neurosciences
Juliet K. Knowles, Haojun Xu, Caroline Soane, Ankita Batra, Tristan Saucedo, Eleanor Frost, Lydia T. Tam, Danielle Fraga, Lijun Ni, Katlin Villar, Sydney Talmi, John R. Huguenard, Michelle Monje
Summary: This study demonstrates that activity-dependent myelination resulting from absence seizures contributes to the progression of epilepsy, suggesting that maladaptive myelination may be pathogenic in certain forms of epilepsy and other neurological diseases.
NATURE NEUROSCIENCE
(2022)
Correction
Multidisciplinary Sciences
Anna V. Elleman, Gabrielle Devienne, Christopher D. Makinson, Allison L. Haynes, John R. Huguenard, J. Du Bois
NATURE COMMUNICATIONS
(2022)
Article
Biology
Brielle Ferguson, Cameron Glick, John R. Huguenard
Summary: Absence seizures are a type of epilepsy characterized by brief periods of unconsciousness and accompanying motor function lapses. These seizures can occur frequently throughout the day and are often accompanied by treatment-resistant attention impairments. In this study, researchers used various techniques to examine the role of prefrontal cortex dysfunction in attention impairments in a mouse model of absence epilepsy. They found altered activity in a specific type of interneuron in the prefrontal cortex, as well as reductions in gamma power during cue presentation. Optogenetic stimulation of these interneurons improved attention performance in the mice, suggesting a potential therapeutic target for cognitive comorbidities in absence epilepsy.
Article
Multidisciplinary Sciences
Eric T. Zhao, Jacob M. Hull, Nofar Mintz Hemed, Hasan Ulusan, Julian Bartram, Anqi Zhang, Pingyu Wang, Albert Pham, Silvia Ronchi, John R. Huguenard, Andreas Hierlemann, Nicholas A. Melosh
Summary: We developed an electrode connector that allows for multithousand channel counts at a millimeter scale by using an ultra-conformable thin-film electrode array. This connector successfully measured action potentials and seizure propagation trajectories in epileptic mice.
Editorial Material
Clinical Neurology
John R. Huguenard
Meeting Abstract
Oncology
Yuan Pan, Jared Hysinger, Tara Barron, Nicki Schindler, Olivia Cobb, Xiaofan Guo, Belgin Yalcin, Corina Anastasaki, Sara Mulinyawe, Anitha Ponnuswami, Suzanne Scheaffer, Yu Ma, Kun-Che Chang, Xin Xia, Joseph Toonen, James Lennon, Erin Gibson, John Huguenard, Linda Liau, Jeffrey Goldberg, Michelle Monje, David Gutmann
Meeting Abstract
Neurosciences
Brielle Ferguson, John Huguenard
NEUROPSYCHOPHARMACOLOGY
(2020)