Regionally selective changes in brain lysosomes occur in the transition from young adulthood to middle age in rats
Section snippets
Experimental procedures
All animal experiments were carried out in accordance with the National Institute of Health guide for the care and use of laboratory animals, and all efforts were made to minimize animal suffering.
Age-related changes in regional levels of cathepsin D
A section processed for cathepsin D immunoreactivity (ir) in the cortical telencephalon of a two-month-old rat is shown in Fig. 1. Labeling was discrete and restricted to cell bodies; with few exceptions, it did not differ across subdivisions to a degree greater than would be expected from variations in cell packing densities. Neurons in cortical layer V (* in Fig. 1A, B), the hilus of the dentate gyrus, and hippocampal pyramidal neurons were more densely stained than cells in the surrounding
Discussion
These results demonstrate that pronounced changes in lysosomes and certain hydrolases develop by middle age in select areas of rat telencephalon. The affected zones correspond to areas of human brain that are particularly vulnerable to aging and Alzheimer's disease. Accordingly, regionally differentiated neurosenescence in humans10., 11., 15., 43. could, in part, be the outcome of a general feature of mammalian brain aging.
The changes in lysosomal size and location in the 12-month animals are
Acknowledgments
The authors thank David Ko, Zain Vally-Mahomed, and Jordan Tran for laboratory assistance. This work is supported by a grant from the National Institute of Aging (AG00538) to G.L.
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