Different types of neural cell death in the cerebellum of the ataxia and male sterility (AMS) mutant mouse.
To investigate the mechanisms(s) of age-dependent atrophy of the cerebellum of the ataxia and male sterility (AMS) mouse at young age, the morphological changes were evaluated and the nature of neural cell death was examined. Dying Purkinje cells lacked characters of classical apoptosis except for light microscopic morphology, but their death was considered to be autonomous death triggered by the direct effect of ams mutation, because of the acute and near-complete disappearance and particular change of the cytoplasm. In contrast, in the granular layer, typical apoptotic bodies were recognized by electron microscopy, and substantial numbers of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end-labeling (TUNEL)-positive cells and activated caspase-3-positive cells were observed. Granule cell death was considered to be target-related apoptosis induced after post-synaptic Purkinje cell death, because the age-dependent changes in TUNEL-positive cell counts followed that of Purkinje cell loss and the peak value was still noted 1 week after total loss of Purkinje cells. These results indicate that both total and partial losses of Purkinje cells and granule cells, respectively, contributed to the atrophy of the AMS cerebellum. Furthermore, different types of neuronal death were recognized; the granule cell death was apoptotic while Purkinje cell death was different from that of classical apoptosis.
Zhou
Li
L
Department of Pathology, Organ Pathology Unit, Shimane University School of Medicine, Izumo, Japan.
Araki
Asuka
A
Nakano
Akinobu
A
Sezer
Cem
C
Harada
Takayuki
T
D000367:Age Factors; D000818:Animals; D001259:Ataxia / Q000235:genetics*; D016923:Cell Death / Q000502:physiology*; D002531:Cerebellum / Q000473:pathology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007248:Infertility, Male / Q000235:genetics*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D046529:Microscopy, Electron, Transmission; D009474:Neurons / Q000473:pathology*