4.4 Article

Brain and spinal cord lesions in 28 inbred strains of aging mice

Journal

VETERINARY PATHOLOGY
Volume 59, Issue 6, Pages 1047-1055

Publisher

SAGE PUBLICATIONS INC
DOI: 10.1177/03009858221120009

Keywords

neuropathology; axonal dystrophy; spheroids; autophagy; gracile nucleus; cuneate nucleus; Hirano-like bodies; mouse; aging

Funding

  1. Ellison Medical Foundation
  2. National Institutes of Health [AG25707]
  3. American Lebanese Syrian Association (ALSAC)

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This study describes the histopathological findings of brain and spinal cord in 20-month-old mice from 28 inbred Jackson Laboratory mouse strains. Common lesions include axonal dystrophy in the sensory tract of the dorsal medulla and mineralization in the thalamus. Most strains showed evidence of impairment of the ubiquitin-proteasome system and/or suspected autophagy.
Brain and spinal cord histopathology findings in male and female 20-month-old mice in a large-scale aging study of 28 inbred Jackson Laboratory mouse strains from 7 genetic families are described. Brain sections from selected strains at 12 and 24 months of age or older were also reviewed. Common lesions include axonal dystrophy in the gracile and/or cuneate nucleus in the sensory tract of the dorsal medulla and in the spinal cord in all strains. Hirano-like bodies were seen in 24/28 strains, and mineralization was observed in the thalamus of 9/28 strains. Less common lesions were also seen in the cerebellum, cerebral cortex, and other brain areas. No brain or spinal cord tumors were found. Evidence of an impairment of the ubiquitin-proteasome system (UPS) and/or suspected autophagy was manifested as medullary axonal dystrophy with intra-axonal granular eosinophilic bodies and LC3B immunohistochemistry in most strains. RIIIS/J, the most severely affected strain, showed moderate axonal dystrophy at 12 months, which progressed to severe lesions at 20 months. Comparative pathology in various species is discussed.

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