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Neurotoxicity studies with a tropomyosin-related kinase A inhibitor, ASP7962, on the sympathetic and sensory nervous systems in rats.
- Source :
-
Toxicology letters [Toxicol Lett] 2021 Jun 15; Vol. 344, pp. 34-45. Date of Electronic Publication: 2021 Mar 02. - Publication Year :
- 2021
-
Abstract
- ASP7962 is a small molecule inhibitor for the nerve growth factor (NGF) receptor, tropomyosin-related kinase A (TrkA). NGF contributes to the survival of sensory and sympathetic neurons through TrkA receptor activation. Gross, microscopic, and quantitative effects to the nervous system were evaluated following oral ASP7962 administration to Sprague Dawley rats for 4 weeks and 13 weeks and after a recovery period. Histopathological findings included reversible neuronal atrophy but no neuronal death in the sympathetic ganglia (cervicothoracic ganglion, cranial mesenteric ganglion or superior [cranial] cervical ganglion). Stereological analysis showed reversible decreased ganglion volume and/or decreased neuron size in the superior (cranial) cervical ganglion in both the 4-week and the 13-week repeated dose studies. There were no test article related changes in the brain, dorsal root ganglia with spinal nerve roots or trigeminal ganglia and no functional deficits. ASP7962 did not cause any detectable dysfunction of the sympathetic and sensory nervous system in either study.<br />Competing Interests: Declaration of Competing Interest Daisuke Kigami, Masahiro Matsumoto and Hiroyuki Ito are employed by Astellas. Astellas conducted these studies at Charles River Laboratories and Tox Path Specialists. Danielle L. Brown and Mark T. Butt contributed to the pathology or stereology assessments as principal investigators, respectively.<br /> (Copyright © 2021 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Dose-Response Relationship, Drug
Drug Administration Schedule
Female
Male
Neurons drug effects
Neurotoxicity Syndromes metabolism
Rats
Rats, Sprague-Dawley
Stellate Ganglion cytology
Stellate Ganglion drug effects
Superior Cervical Ganglion cytology
Superior Cervical Ganglion drug effects
Trigeminal Ganglion drug effects
Neurons, Afferent drug effects
Receptor, trkA antagonists & inhibitors
Sympathetic Nervous System drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1879-3169
- Volume :
- 344
- Database :
- MEDLINE
- Journal :
- Toxicology letters
- Publication Type :
- Academic Journal
- Accession number :
- 33667609
- Full Text :
- https://doi.org/10.1016/j.toxlet.2021.02.018