Journal article
Aging‐related alterations in the distribution of Ca2+‐dependent PKC isoforms in rabbit hippocampus
Hippocampus, Vol.14(7), pp.849-860
2004
Handle:
https://hdl.handle.net/2376/106132
PMID: 15382255
Abstract
The immunocytochemical and subcellular localization of the Ca2+‐dependent protein kinase C (cPKC) isoforms (PKCα, β1, β2, and γ) was examined in rabbit hippocampus of young (3 months of age; n = 11) and aging (36 months of age; n = 14) subjects. Detailed immunocytochemical analyses revealed a significant increase in PKCβ1, β2, and γ immunoreactivity in principal cell bodies and associated dendrites, and interneurons of the hilar region in the aging rabbits. The number of PKCα‐ and γ‐positive interneurons in the aging stratum oriens declined significantly. PKCα was least affected in principal cells, showing an increase in immunostaining in granule cells only. Weakly PKC‐positive principal cells intermingled between densely stained ones were seen in parts of the hippocampus in most of the aging rabbits, showing that the degree of aging‐related alterations in PKC‐immunoreactivity varies between neurons. Changes in PKC expression in the molecular and subgranular layer of the aging dentate gyrus suggested a reorganization of PKC‐positive afferents to this region. Western blot analysis revealed a significant loss of PKC in the pellet fraction for all isoforms, and a tendency for increased levels of cytosolic PKC. However, no significant changes were found in total PKC content for any PKC isoform. A concurrent dramatic loss of the PKC anchoring protein receptor for activated C kinase (RACK1) in the pellet fraction was shown by Western blotting. These findings suggest that the loss of RACK1 contributes to the dysregulation of the PKC system in the aging rabbit hippocampus. The enhanced PKC‐immunoreactivity might relate to reduced protein‐protein interactions of PKC with the anchoring protein RACK1 leading to increased access of the antibodies to the antigenic site. In conclusion, the results suggest that memory deficits in aging rabbits are (in part) caused by dysregulation of subcellular PKC localization in hippocampal neurons. © 2004 Wiley‐Liss, Inc.
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Details
- Title
- Aging‐related alterations in the distribution of Ca2+‐dependent PKC isoforms in rabbit hippocampus
- Creators
- E.A Van der ZeeI.F PalmM O'ConnorE.T MaizelsM Hunzicker‐DunnJ.F Disterhoft
- Publication Details
- Hippocampus, Vol.14(7), pp.849-860
- Academic Unit
- Molecular Biosciences, School of
- Publisher
- Wiley Subscription Services, Inc., A Wiley Company; Hoboken
- Number of pages
- 12
- Grant note
- National Institutes of Health (R37 AG08796)
- Identifiers
- 99900546765701842
- Language
- English
- Resource Type
- Journal article