Early-onset torsion dystonia (TOR1A/DYT1) is a devastating hereditary motor disorder whose pathophysiology remains unclear. Studies in transgenic mice suggested abnormal cholinergic transmission in the putamen, but this has not yet been demonstrated in humans. The role of the cerebellum in the pathophysiology of the disease has also been highlighted but the involvement of the intrinsic cerebellar cholinergic system is unknown. In this study, cholinergic neurons were imaged using PET with 18F-fluoroethoxybenzovesamicol, a radioligand of the vesicular acetylcholine transporter (VAChT). Here, we found an age-related decrease in VAChT expression in the posterior putamen and caudate nucleus of DYT1 patients versus matched controls, with low expression in young but not in older patients. In the cerebellar vermis, VAChT expression was also significantly decreased in patients versus controls, but independently of age. Functional connectivity within the motor network studied in MRI and the interregional correlation of VAChT expression studied in PET were also altered in patients. These results show that the cholinergic system is disrupted in the brain of DYT1 patients and is modulated over time through plasticity or compensatory mechanisms.
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Muscle Nerve
December 2024
Department of Mechanical Engineering, Faculty of Science and Technology, Keio University, Yokohama, Kanagawa, Japan.
Introduction/aims: VAChT-Cre is a transgenic mouse line targeting slow-twitch fatigue-resistant and fast-twitch fatigue-resistant motor neurons that innervate oxidative type I and type IIa muscle fibers. To ablate these neurons, VAChT-Cre mice were crossbred with NSE-DTA mice, leading to the expression of diphtheria toxin A after Cre-mediated excision. The resulting VAChT-Cre;NSE-DTA mice exhibited motor deficits, abnormal locomotion, muscular atrophy, and tremor, making them a useful model for studying motor neuron physiology and pathology.
View Article and Find Full Text PDFCell Tissue Res
November 2024
Department of Physiology and Cell Biology, University of Nevada, Reno School of Medicine, 1664 N. Virginia St., MS 352, Reno, NV, 89557, USA.
Interstitial cells of Cajal (ICC) and PDGFRα cells regulate smooth muscle motility in the gastrointestinal (GI) tract, yet their function in the esophagus remains unknown. The mouse esophagus has been described as primarily skeletal muscle; however, ICC have been identified in this region. This study characterizes the distribution of skeletal and smooth muscle cells (SMCs) and their spatial relationship to ICC, PDGFRα cells, and intramuscular motor neurons in the mouse esophagus.
View Article and Find Full Text PDFAppl Microbiol Biotechnol
October 2024
Department of Life Sciences, National Chung Hsing University, No. 145, Xing-Da Road, South District, Taichung City, 40227, Taiwan, ROC.
Melittin is a bioactive peptide and the predominant component in bee venom (BV), studied for its many medical properties, such as antibacterial, anti-inflammatory, anti-arthritis, nerve damage reduction, and muscle cell regeneration. Melittin is primarily obtained through natural extraction and chemical synthesis; however, both methods have limitations and cannot be used for mass production. This study established a heterologous melittin expression system in the probiotic yeast Kluyveromyces marxianus.
View Article and Find Full Text PDFNat Commun
October 2024
Neuroscience Graduate Program, Western University, London, Ontario, Canada.
Cortical cholinergic projections originate from subregions of the basal forebrain (BF). To examine its organization in humans, we computed multimodal gradients of BF connectivity by combining 7 T diffusion and resting state functional MRI. Moving from anteromedial to posterolateral BF, we observe reduced tethering between structural and functional connectivity gradients, with the lowest tethering in the nucleus basalis of Meynert.
View Article and Find Full Text PDFNeurourol Urodyn
January 2025
Second Department of Gynecology, Medical University of Lublin, Lublin, Poland.
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