Purkinje Cells Are More Vulnerable to the Specific Depletion of Cathepsin D Than to That of Atg7.

Purkinje Cells Are More Vulnerable to the Specific Depletion of Cathepsin D Than to That of Atg7.
Am J Pathol. 2017 May 11;:
Authors: Koike M, Shibata M, Sunabori T, Yamaguchi J, Sakimura K, Komatsu M, Tanaka K, Uchiyama Y
Abstract
Neurologic phenotypes of cathepsin D (CTSD)-deficient mice, a murine model of neuronal ceroid lipofuscinoses, indicate the importance of CTSD for the maintenance of metabolism in central nervous system neurons. To further understand the role of CTSD in central nervous system neurons, we generated mice with a CTSD deficiency specifically in the Purkinje cells (PCs) (CTSD(Flox/Flox);GRID2-Cre) and compared their phenotypes with those of PC-selective Atg7-deficient (Atg7(Flox/Flox);GRID2-Cre) mice. In both strains of mice, PCs underwent degeneration, but the CTSD-deficient PCs disappeared more rapidly than their Atg7-deficient counterparts. When CTSD-deficient PCs died, the neuronal cell bodies became shrunken, filled with autophagosomes and autolysosomes, and had nuclei with dispersed small chromatin fragments. The dying Atg7-deficient PCs also showed similar ultrastructures, indicating that the neuronal cell death of CTSD- and Atg7-deficient PCs was distinct from apoptosis. Immunohistochemical observations showed the formation of calbindin-positive axonal spheroids and the swelling of vesicular GABA transporter-positive presynaptic terminals that were more pronounced in Atg7-deficient PCs than in CTSD-defic...

Source: The American Journal of Pathology - May 11, 2017 Category: Pathology Authors: Koike M, Shibata M, Sunabori T, Yamaguchi J, Sakimura K, Komatsu M, Tanaka K, Uchiyama Y Tags: Am J Pathol Source Type: research