Lysosomal Dysfunction Results in Lamina-Specific Meganeurite Formation but Not Apoptosis in Frontal Cortex

Authors: Yong A.P.¹; Bednarski E.²; Gall C.M.¹; Lynch G.^{2, 3}; Ribak C.E.¹

Source: Experimental Neurology, Volume 157, Number 1, May 1999 , pp. 150-160(11)

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Abstract:

An inhibitor of cathepsins B and L was used to test if lysosomal dysfunction in cultured slices of rat frontal cortex induces pathological features that develop in the human cortex during aging and Alzheimer's disease (AD). Incubation for 6 days with N-CBZ-l-phenylalanyl-l-alanine-diazomethylketone (ZPAD) resulted in a massive proliferation of endosomes-lysosomes in all cortical layers. Slices additionally exposed to a washout of 4 days had numerous meganeurites, blister-like structures in the region of the axon hillock, in layer III but not in other cortical laminae. Meganeurites are a characteristic feature of the human frontal cortex after age 50 and are largely restricted to layer III. Tests for apoptosis were carried out at two intervals following meganeurite formation. TUNEL-labeled neurons were confined to layers II/III on the surface of the slices but there was no evidence for a ZPAD effect. In all, 6 days of lysosomal dysfunction reproduces characteristic effects of normal aging in neocortex without generating some key features of AD. Copyright 1999 Academic Press.

Language: English

Document Type: Research article

Affiliations: 1: Department of Anatomy and Neurobiology 2: Department of Anatomy and Neurobiology, Center for the Neurobiology of Learning and Memory 3: Department of Anatomy and Neurobiology, Center for the Neurobiology of Learning and Memory, Department of Psychiatry, University of California, Irvine, California, 92697

Publication date: 1999-05-01