Article
Multidisciplinary Sciences
Ze Zhang, Yehua Li, Xueyuan Lv, Linlin Zhao, Xiaodong Wang
Summary: The study revealed that activation of ventrolateral medulla (VLM) catecholaminergic (CA) neurons in the mouse brain significantly alters tumor growth in various tumor models. Specific ablation or inhibition of these neurons slows down tumor progression, while chemogenetic activation promotes tumor growth. The regulatory effect of VLM CA neuron ablation on tumors is mediated by the adaptive immune system, as shown by experiments with immune-deficient mice and CD8* T cell depletion. Additionally, VLM CA neuronal ablation has an additive antitumor effect when combined with paclitaxel treatment.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Neurosciences
Lisa Rauschenberger, Esther-Marie Krenig, Alea Stengl, Susanne Knorr, Tristan H. Harder, Felix Steeg, Maximilian U. Friedrich, Kathrin Grundmann-Hauser, Jens Volkmann, Chi Wang Ip
Summary: The relationship between genotype and phenotype in DYT-TOR1A dystonia as well as the associated motor circuit alterations are still not fully understood. This study provides evidence that recovery from a peripheral nerve injury can trigger a dystonic phenotype in genetically predisposed mice. The analysis of neural structures and neurochemical abnormalities in the basal ganglia highlights the importance of extragenetic factors in the symptomatogenesis of DYT-TOR1A dystonia.
NEUROBIOLOGY OF DISEASE
(2023)
Article
Cell Biology
Kimberley Reid, Dora Steel, Sanjana Nair, Sanjay Bhate, Lorenzo Biassoni, Sniya Sudhakar, Michelle Heys, Elizabeth Burke, Erik-Jan Kamsteeg, Biju E. Hameed, Michael Zech, Niccolo Mencacci, Katy A. Barwick, Maya Topf, Manju Kurian
Summary: In this study, a patient with severe infantile parkinsonism-dystonia was reported, exhibiting clinical features of dopamine deficiency. Whole-genome sequencing identified a homozygous variant in the DRD1 gene, resulting in loss of function of the D-1 receptor. The findings highlight the crucial role of the D-1 receptor in motor control.
Editorial Material
Cell Biology
Barbara Juarez, Larry S. Zweifel
Summary: The medium spiny neurons in the NAc region regulate the activity of ventral mesencephalic dopamine neurons to drive reward or aversion through direct or indirect projections.
Editorial Material
Cell & Tissue Engineering
Jun Takahashi
Summary: These two papers demonstrate the induction of dopaminergic neurons from human embryonic stem cells and lay the foundation for future clinical trials.
Article
Biochemistry & Molecular Biology
Yasumi Ohta, Takaaki E. Murakami, Mamiko Kawahara, Makito Haruta, Hironari Takehara, Hiroyuki Tashiro, Kiyotaka Sasagawa, Jun Ohta, Metin Akay, Yasemin M. Akay
Summary: This study confirms the importance of dopamine in reward behavior, as well as the interaction between dopaminergic and GABAergic neurons. The researchers used optogenetics to stimulate neurons in mice and measured dopamine release. The results show that different stimulation frequencies have different effects on dopamine release, and GABAergic neurons have an inhibitory effect on dopamine activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Gunasingh Jeyaraj Masilamoni, Allison Weinkle, Stella M. Papa, Yoland Smith
Summary: This study found decreased serotonergic and catecholaminergic innervation in the frontal cortex at early stages of Parkinson's disease. The use of MPTP-treated monkeys as animal models revealed that these changes may contribute to early non-motor symptoms in PD.
Article
Biochemistry & Molecular Biology
Raj Kamal Srivastava, Inigo Ruiz de Azua, Andrea Conrad, Martin Purrio, Beat Lutz
Summary: This study found that the deletion of CB1 in dbh-positive cells prevents diet-induced obesity through multiple mechanisms including increased sympathetic nervous system activity, reduced NPY activity, and decreased basal hypothalamic-pituitary-adrenal axis activity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Editorial Material
Cell & Tissue Engineering
Roger A. Barker, Gerard J. Boer, Elena Cattaneo, R. Alta Charo, Susana M. Chuva de Sousa Lopes, Yali Cong, Misao Fujita, Steven Goldman, Goran Hermeren, Insoo Hyun, Steven Lisgo, Anne E. Rosser, Eric Anthony, Olle Lindvall
Summary: The ISSCR has developed informed consent standards for human fetal tissue donation and research to ensure consistency, transparency, and public reassurance.
Article
Chemistry, Analytical
Zeping Zuo, Ting Kang, Shilong Hu, Wuyue Su, Yu Gan, Zhuang Miao, Hanqing Zhao, Ping Feng, Bowen Ke, Minyong Li
Summary: In this study, a turn-on NE bioluminescent probe (NBP) was successfully developed for the real-time and noninvasive detection of norepinephrine as a tracer. The NBP exhibited high sensitivity and selectivity in vitro, and provided a promising strategy for in vivo imaging of NE in living animals.
ANALYTICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Kouji Fukuyama, Tomosuke Nakano, Takashi Shiroyama, Motohiro Okada
Summary: This study demonstrates that the selective alpha 2A adrenoceptor agonist guanfacine has dual actions on catecholaminergic transmission, with acute attenuation of noradrenergic transmission and chronic enhancement of noradrenergic transmission and thalamocortical glutamatergic transmission. These dual actions likely contribute to the clinical effects of guanfacine against ADHD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Jayantee Kalita, Abhilasha Tripathi, Mahesh Jadhav, Ravindra S. Thakur, Devendra K. Patel
Summary: Movement disorder is an important manifestation of neurologic Wilson disease, but there is little information on dopaminergic pathways. In this study, we evaluate dopamine and its receptors in patients with NWD and correlate the changes with movement disorder and MRI changes.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Medicine, General & Internal
Uta Hoppmann, Harald Engler, Sabrina Krause, Edit Rottler, Julia Hoech, Franziska Szabo, Peter Radermacher, Christiane Waller
Summary: This study aimed to elucidate the impact of social stress on the CA system and inflammation markers in patients suffering from CAD and depression. The results showed that patients with both CAD and depression exhibited significantly lower epinephrine and dopamine levels compared to other groups at baseline.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Multidisciplinary Sciences
Clement Solie, Alessandro Contestabile, Pedro Espinosa, Stefano Musardo, Sebastiano Bariselli, Chieko Huber, Alan Carleton, Camilla Bellone
Summary: This study shows that the pathway from superior colliculus to ventral tegmental area (VTA) plays a key role in encoding orienting behavior and modulating social interaction. The researchers found that this pathway affects VTA dopamine neurons projecting onto dorsolateral striatum, and the stimulation or inhibition of this pathway can influence social interaction in mice.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Matheus C. Bianchini, Luiz F. W. Soares, Joao M. F. M. Sousa, Bruna P. Ramborger, Mateus C. Gayer, Jessika C. Bridi, Rafael Roehrs, Simone Pinton, Michael Aschner, Daiana S. Avila, Robson L. Puntel
Summary: This study found that exposure to methylmercury in fruit flies led to reduced survival rate, decreased levels of dopamine and octopamine, and changes in behavior. These effects were associated with inhibition of acetylcholinesterase and tyrosine hydroxylase, increased oxidative stress, and altered glutathione-S-transferase activity.
CHEMICO-BIOLOGICAL INTERACTIONS
(2022)
Review
Biochemistry & Molecular Biology
Luis Bonet-Ponce, Mark R. Cookson
Summary: Protein coding mutations in LRRK2 cause familial Parkinson's disease, while noncoding variations increase the risk of sporadic PD. These mutations increase LRRK2 kinase activity, influencing intracellular membrane trafficking.
Article
Biochemistry & Molecular Biology
Nicole J. Van Bergen, Katrina M. Bell, Kirsty Carey, Russell Gear, Sean Massey, Edward K. Murrell, Lyndon Gallacher, Kate Pope, Paul J. Lockhart, Andrew Kornberg, Lynn Pais, Marzena Walkiewicz, Cas Simons, Mcri Rare Diseases Flagship, Vihandha O. Wickramasinghe, Susan M. White, John Christodoulou
Summary: The nuclear pore complex (NPC) is essential for transporting macromolecules between the nucleus and cytoplasm, and genetic variants in components like TPR can cause neurological disorders. Variants in TPR were found to decrease TPR levels in patient fibroblasts, leading to NPC density reduction and global RNA intensity decrease in the nucleus, linking TPR variants to the neurological disorder in the siblings.
HUMAN MOLECULAR GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Timothy E. Green, Joshua E. Motelow, Mark F. Bennett, Zimeng Ye, Caitlin A. Bennett, Nicole G. Griffin, John A. Damiano, Richard J. Leventer, Jeremy L. Freeman, A. Simon Harvey, Paul J. Lockhart, Lynette G. Sadleir, Amber Boys, Ingrid E. Scheffer, Heather Major, Benjamin W. Darbro, Melanie Bahlo, David B. Goldstein, John F. Kerrigan, Erin L. Heinzen, Samuel F. Berkovic, Michael S. Hildebrand
Summary: We identified bi-allelic variants in cilia genes and single somatic variants in known disease genes in hypothalamic hamartoma patients, expanding our understanding of the genetic architecture and reconceptualizing the disorder as a ciliopathy.
HUMAN MOLECULAR GENETICS
(2022)
Article
Clinical Neurology
Mathieu Barbier, Melanie Bahlo, Alessandra Pennisi, Maxime Jacoupy, Rick M. Tankard, Claire Ewenczyk, Kayli C. Davies, Patricia Lino-Coulon, Claire Colace, Haloom Rafehi, Nicolas Auger, Brendan R. E. Ansell, Ivo van der Stelt, Katherine B. Howell, Marie Coutelier, David J. Amor, Emeline Mundwiller, Lena Guillot-Noel, Elsdon Storey, R. J. McKinlay Gardner, Mathew J. Wallis, Alfredo Brusco, Olga Corti, Agnes Rotig, Richard J. Leventer, Alexis Brice, Martin B. Delatycki, Giovanni Stevanin, Paul J. Lockhart, Alexandra Durr
Summary: This study identifies PNPT1 as a new causal gene for SCA25 and highlights the biological links between alterations of mtRNA trafficking, interferonopathies and ataxia.
ANNALS OF NEUROLOGY
(2022)
Article
Genetics & Heredity
Jacqueline M. Ogier, Yujing Gao, Eileen M. Dunne, Michael A. Wilson, Sarath C. Ranganathan, Gregory H. Tesch, David JNikolic Paterson, Alain Dabdoub, Rachel A. Burt, Bryony A. Nayagam, Paul J. Lockhart
Summary: Aminoglycoside antibiotics can cause toxic effects on the sensory hair cells in the inner ear, leading to permanent hearing loss and vestibular impairment. This study investigates the potential of ASK1 inhibition as a novel strategy to prevent aminoglycoside ototoxicity, providing significant pre-clinical evidence.
JOURNAL OF MOLECULAR MEDICINE-JMM
(2022)
Editorial Material
Clinical Neurology
Paul Lockhart
Article
Clinical Neurology
Nataliya Di Donato, Renzo Guerrini, Charles J. Billington, A. James Barkovich, Philine Dinkel, Elena Freri, Michael Heide, Elliot S. Gershon, Tracy S. Gertler, Robert J. Hopkin, Suma Jacob, Sarah K. Keedy, Daniz Kooshavar, Paul J. Lockhart, Dietmar R. Lohmann, Iman G. Mahmoud, Elena Parrini, Evelin Schrock, Giulia Severi, Andrew E. Timms, Richard Webster, Mary J. H. Willis, Maha S. Zaki, Joseph G. Gleeson, Richard J. Leventer, William B. Dobyns
Summary: Reelin, encoded by the RELN gene, is critical for brain development and function. Variants in RELN have been associated with various neurodevelopmental disorders, including lissencephaly and potentially schizophrenia. This study provides data on individuals with biallelic and monoallelic RELN variants, expanding the spectrum of associated phenotypes.
Article
Biochemistry & Molecular Biology
Haloom Rafehi, Cherie Green, Kiymet Bozaoglu, Greta Gillies, Martin B. Delatycki, Paul J. Lockhart, Ingrid E. Scheffer, Melanie Bahlo
Summary: This study identified a family with myotonic dystrophy type 2 caused by an expansion of a specific STR, which could be detected through screening of WGS datasets. The findings have implications for diagnosis and genetic counseling.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2023)
Letter
Clinical Neurology
Wei Shern Lee, Richard J. Leventer, Paul J. Lockhart
Article
Genetics & Heredity
C. A. Stutterd, A. Vanderver, P. J. Lockhart, G. Helman, K. Pope, E. Uebergang, C. Love, M. B. Delatycki, D. Thorburn, M. T. Mackay, H. Peters, A. J. Kornberg, C. Patel, V Rodriguez-Casero, M. Waak, J. Silberstein, A. Sinclair, M. Nolan, M. Field, M. R. Davis, M. Fahey, I. E. Scheffer, J. L. Freeman, N. Wolf, R. J. Taft, M. S. van der Knaap, C. Simons, R. J. Leventer
Summary: This study identified the genetic causes of unclassified white matter disorders through deep phenotyping and genome sequencing, and found that broad genomic testing is crucial for diagnosing white matter diseases.
EUROPEAN JOURNAL OF MEDICAL GENETICS
(2022)
Article
Clinical Neurology
Emma Macdonald-Laurs, Aaron E. L. Warren, Wei Shern Lee, Joseph Yuan-Mou Yang, Duncan MacGregor, Paul J. Lockhart, Richard J. Leventer, Andrew Neal, A. Simon Harvey
Summary: The distribution of epileptogenicity and dysplasia in and around bottom-of-sulcus dysplasia (BOSD) was assessed to better understand the clinical outcome and optimal surgical approach. The study found that dysplasia and intrinsic epileptogenicity are mostly limited to the dysplastic sulcus, and abnormalities in surrounding cortex are secondary phenomena.
Article
Clinical Neurology
Wei Shern Lee, Emma Macdonald-Laurs, Sarah E. M. Stephenson, Colleen D'Arcy, Duncan MacGregor, Richard J. Leventer, Wirginia Maixner, A. Simon Harvey, Paul J. Lockhart
Summary: Pathogenic somatic MTOR variants in the cerebral cortex are a common cause of focal cortical dysplasia (FCD). We present a case of a child with drug and surgery-resistant focal epilepsy due to FCD type II who exhibited progressive enlargement and abnormal signals in the ipsilateral caudate and lentiform nuclei. Genetic analysis revealed a somatic MTOR variant in the caudate nucleus, providing a potential explanation for persistent seizures despite apparent resection or disconnection of the dysplastic hemisphere.
Article
Clinical Neurology
Wei Shern Lee, Emma Macdonald-Laurs, Sarah Stephenson, Colleen D'Arcy, Wirginia Maixner, A. Simon Harvey, Paul J. J. Lockhart, Richard J. J. Leventer
Summary: This study describes a child with diagnosed tuberous sclerosis complex (TSC) who carries a pathogenic somatic variant in RHEB, but no pathogenic variants in the known TSC genes, TSC1 or TSC2. The findings suggest that variants in RHEB may explain some genetically undiagnosed TSC cases, potentially making it the third gene for TSC, or TSC3.
Article
Cell & Tissue Engineering
Kayli C. Daviesa, Kiymet Bozaoglu, Paul J. Lockhart
Summary: We generated patient iPSC lines with homozygous AAGGG expansions and gene corrected iPSC lines using reprogramming and CRISPR-Cas9 genome editing. These lines expressed pluripotency markers, had normal karyotype, and could differentiate into all three germ layers. These mutant and corrected iPSC lines provide a valuable tool for studying the molecular mechanisms underlying CANVAS.
STEM CELL RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Justin L. Read, Kayli C. Davies, Genevieve C. Thompson, Martin B. Delatycki, Paul J. Lockhart
Summary: Tandem repeat DNA sequences play a significant role in the human genome, but their polymorphic nature can lead to disease. Advances in sequencing and bioinformatics tools are enabling high throughput testing for repeat expansion disorders, offering new opportunities for diagnosis and research.
EMERGING TOPICS IN LIFE SCIENCES
(2023)
Article
Neurosciences
Yang He, Jun Tang, Meng Zhang, Junjie Ying, Dezhi Mu
Summary: This study investigated the protective effects and mechanisms of human placenta derived mesenchymal stem cells (hPMSCs) transplantation in a rat model of hypoxic-ischemic encephalopathy (HIE). The results showed that hPMSCs transplantation reduced apoptosis and improved long-term neurological prognosis. Furthermore, the downregulation of Sema 3A/NRP-1 expression and activation of the PI3K/Akt/mTOR signaling pathway played a key role in the protective effects of hPMSCs.
Article
Neurosciences
Emily L. Isenstein, Edward G. Freedman, Jiayi Xu, Ian A. DeAndrea-Lazarus, John J. Foxe
Summary: This study evaluated electrophysiological discrimination of parametric somatosensory stimuli in healthy young adults to understand how the brain processes the duration of tactile information. The results showed that participants did not electrophysiologically discriminate between 100 and 115 ms, but they exhibited distinct electrophysiological responses when the deviant stimuli were 130, 145, and 160 ms. These findings contribute to a better understanding of tactile sensitivity in different clinical conditions.
Article
Neurosciences
Juliana R. Souza, Ludmila Lima-Silveira, Daniela Accorsi-Mendonca, Benedito H. Machado
Summary: This study demonstrates that A2A receptors play a crucial role in modulating synaptic transmission in the NTS neurons and are required for the enhancement of glutamatergic transmission observed under short-term sustained hypoxia conditions.
Article
Neurosciences
Miki Hashizume, Rina Ito, Rie Suge, Yasushi Hojo, Gen Murakami, Takayuki Murakoshi
Summary: The basolateral amygdaloid complex (BLA) is closely involved in the formation of emotional memories, including both aversive memory and contextual fear memory. Acute sleep deprivation (SD) disrupts the acquisition of tone-associated fear memory in juvenile rats, but has no significant effect on contextual fear memory. Slow network oscillation in the amygdala contributes to the formation of amygdala-dependent fear memory in relation to sleep.
Article
Neurosciences
Qunxian Wang, Shipeng Guo, Dongjie Hu, Xiangjun Dong, Zijun Meng, Yanshuang Jiang, Zijuan Feng, Weihui Zhou, Weihong Song
Summary: GSDME plays a crucial role in the pathogenesis of Alzheimer's disease by regulating the switch from apoptosis to pyroptosis and participating in neuroinflammatory response. Knockdown of GSDME has been shown to improve cognitive impairments, indicating that GSDME could be a therapeutic target for Alzheimer's disease.
