دورية أكاديمية

Cerebellar axonopathy in Shivers horses identified by spatial transcriptomic and proteomic analyses

التفاصيل البيبلوغرافية
العنوان: Cerebellar axonopathy in Shivers horses identified by spatial transcriptomic and proteomic analyses
المؤلفون: Stephanie J. Valberg, Zoë J. Williams, Marisa L. Henry, Carrie J. Finno
المصدر: Journal of Veterinary Internal Medicine, Vol 37, Iss 4, Pp 1568-1579 (2023)
بيانات النشر: Wiley, 2023.
سنة النشر: 2023
المجموعة: LCC:Veterinary medicine
مصطلحات موضوعية: gene expression, movement disorder, neurology, protein expression, shivering, Veterinary medicine, SF600-1100
الوصف: Abstract Background Shivers in horses is characterized by abnormal hindlimb movement when walking backward and is proposed to be caused by a Purkinje cell (PC) axonopathy based on histopathology. Objectives Define region‐specific differences in gene expression within the lateral cerebellar hemisphere and compare cerebellar protein expression between Shivers horses and controls. Animals Case‐control study of 5 Shivers and 4 control geldings ≥16.2 hands in height. Methods Using spatial transcriptomics, gene expression was compared between Shivers and control horses in PC soma and lateral cerebellar hemisphere white matter, consisting primarily of axons. Tandem‐mass‐tag (TMT‐11) proteomic analysis was performed on lateral cerebellar hemisphere homogenates. Results Differences in gene expression between Shivers and control horses were evident in principal component analysis of axon‐containing white matter but not PC soma. In white matter, there were 455/1846 differentially expressed genes (DEG; 350 ↓DEG, 105 ↑DEG) between Shivers and controls, with significant gene set enrichment of the Toll‐Like Receptor 4 (TLR4) cascade, highlighting neuroinflammation. There were 50/936 differentially expressed proteins (DEP). The 27 ↓DEP highlighted loss of axonal proteins including intermediate filaments (5), myelin (3), cytoskeleton (2), neurite outgrowth (2), and Na/K ATPase (1). The 23 ↑DEP were involved in the extracellular matrix (7), cytoskeleton (7), redox balance (2), neurite outgrowth (1), signal transduction (1), and others. Conclusion and Clinical Importance Our findings support axonal degeneration as a characteristic feature of Shivers. Combined with histopathology, these findings are consistent with the known distinctive response of PC to injury where axonal changes occur without a substantial impact on PC soma.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1939-1676
0891-6640
Relation: https://doaj.org/toc/0891-6640; https://doaj.org/toc/1939-1676
DOI: 10.1111/jvim.16784
URL الوصول: https://doaj.org/article/96e211f42059424bb9535301597cba69
رقم الأكسشن: edsdoj.96e211f42059424bb9535301597cba69
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:19391676
08916640
DOI:10.1111/jvim.16784