Aging-related alterations in the distribution of Ca2+-dependent PKC isoforms in rabbit hippocampus

E. A. Van de Zee; I. F. Palm; M. O'Connor; E. T. Maizels; M. Hunzicker-Dunn; J. F. Disterhoft

doi:10.1002/hipo.20000

Aging-related alterations in the distribution of Ca²⁺-dependent PKC isoforms in rabbit hippocampus

E. A. Van de Zee, I. F. Palm, M. O'Connor, E. T. Maizels, M. Hunzicker-Dunn, J. F. Disterhoft

Neuroscience

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

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.

Original language	English (US)
Pages (from-to)	849-860
Number of pages	12
Journal	Hippocampus
Volume	14
Issue number	7
DOIs	https://doi.org/10.1002/hipo.20000
State	Published - 2004

Keywords

Immunocytochemistry
Memory
Protein kinase C
RACK1
Western blot

ASJC Scopus subject areas

Cognitive Neuroscience

Access to Document

10.1002/hipo.20000

Cite this

@article{483c790e711140cd81e20c80bda672fa,

title = "Aging-related alterations in the distribution of Ca2+-dependent PKC isoforms in rabbit hippocampus",

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.",

keywords = "Immunocytochemistry, Memory, Protein kinase C, RACK1, Western blot",

author = "{Van de Zee}, {E. A.} and Palm, {I. F.} and M. O'Connor and Maizels, {E. T.} and M. Hunzicker-Dunn and Disterhoft, {J. F.}",

year = "2004",

doi = "10.1002/hipo.20000",

language = "English (US)",

volume = "14",

pages = "849--860",

journal = "Hippocampus",

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number = "7",

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TY - JOUR

T1 - Aging-related alterations in the distribution of Ca2+-dependent PKC isoforms in rabbit hippocampus

AU - Van de Zee, E. A.

AU - Palm, I. F.

AU - O'Connor, M.

AU - Maizels, E. T.

AU - Hunzicker-Dunn, M.

AU - Disterhoft, J. F.

PY - 2004

Y1 - 2004

N2 - 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.

AB - 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.

KW - Immunocytochemistry

KW - Memory

KW - Protein kinase C

KW - RACK1

KW - Western blot

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