CREB-binding protein levels in the rat hippocampus fail to predict chronological or cognitive aging

Inês Tomás Pereira, Christopher E. Coletta, Evelyn V. Perez, David H. Kim, Michela Gallagher, Ilya G. Goldberg, Peter R. Rapp

Research output: Contribution to journalArticle

Abstract

Normal cognitive aging is associated with deficits in memory processes dependent on the hippocampus, along with large-scale changes in the hippocampal expression of many genes. Histone acetylation can broadly influence gene expression and has been recently linked to learning and memory. We hypothesized that CREB-binding protein (CBP), a key histone acetyltransferase, may contribute to memory decline in normal aging. Here, we quantified CBP protein levels in the hippocampus of young, aged unimpaired, and aged impaired rats, classified on the basis of spatial memory capacity documented in the Morris water maze. First, CBP-immunofluorescence was quantified across the principal cell layers of the hippocampus using both low and high resolution laser scanning imaging approaches. Second, digital images of CBP immunostaining were analyzed by a multipurpose classifier algorithm with validated sensitivity across many types of input materials. Finally, CBP protein levels in the principal subfields of the hippocampus were quantified by quantitative Western blotting. CBP levels were equivalent as a function of age and cognitive status in all analyses. The sensitivity of the techniques used was substantial, sufficient to reveal differences across the principal cell fields of the hippocampus, and to correctly classify images from young and aged animals independent of CBP immunoreactivity. The results are discussed in the context of recent evidence suggesting that CBP decreases may be most relevant in conditions of aging that, unlike normal cognitive aging, involve significant neuron loss.

Original languageEnglish (US)
Pages (from-to)832-844
Number of pages13
JournalNeurobiology of Aging
Volume34
Issue number3
DOIs
StatePublished - Mar 2013

Fingerprint

CREB-Binding Protein
Hippocampus
Histone Acetyltransferases
Gene Expression
Cognitive Aging
Memory Disorders
Acetylation
Histones
Cognition
Fluorescent Antibody Technique
Proteins
Lasers
Western Blotting
Learning
Neurons
Water

Keywords

  • Epigenetics
  • Image analysis
  • Memory
  • Quantitative microscopy

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Aging
  • Developmental Biology
  • Geriatrics and Gerontology

Cite this

CREB-binding protein levels in the rat hippocampus fail to predict chronological or cognitive aging. / Tomás Pereira, Inês; Coletta, Christopher E.; Perez, Evelyn V.; Kim, David H.; Gallagher, Michela; Goldberg, Ilya G.; Rapp, Peter R.

In: Neurobiology of Aging, Vol. 34, No. 3, 03.2013, p. 832-844.

Research output: Contribution to journalArticle

Tomás Pereira, Inês ; Coletta, Christopher E. ; Perez, Evelyn V. ; Kim, David H. ; Gallagher, Michela ; Goldberg, Ilya G. ; Rapp, Peter R. / CREB-binding protein levels in the rat hippocampus fail to predict chronological or cognitive aging. In: Neurobiology of Aging. 2013 ; Vol. 34, No. 3. pp. 832-844.
@article{6fe09323757c4528a1f6e045c5fec004,
title = "CREB-binding protein levels in the rat hippocampus fail to predict chronological or cognitive aging",
abstract = "Normal cognitive aging is associated with deficits in memory processes dependent on the hippocampus, along with large-scale changes in the hippocampal expression of many genes. Histone acetylation can broadly influence gene expression and has been recently linked to learning and memory. We hypothesized that CREB-binding protein (CBP), a key histone acetyltransferase, may contribute to memory decline in normal aging. Here, we quantified CBP protein levels in the hippocampus of young, aged unimpaired, and aged impaired rats, classified on the basis of spatial memory capacity documented in the Morris water maze. First, CBP-immunofluorescence was quantified across the principal cell layers of the hippocampus using both low and high resolution laser scanning imaging approaches. Second, digital images of CBP immunostaining were analyzed by a multipurpose classifier algorithm with validated sensitivity across many types of input materials. Finally, CBP protein levels in the principal subfields of the hippocampus were quantified by quantitative Western blotting. CBP levels were equivalent as a function of age and cognitive status in all analyses. The sensitivity of the techniques used was substantial, sufficient to reveal differences across the principal cell fields of the hippocampus, and to correctly classify images from young and aged animals independent of CBP immunoreactivity. The results are discussed in the context of recent evidence suggesting that CBP decreases may be most relevant in conditions of aging that, unlike normal cognitive aging, involve significant neuron loss.",
keywords = "Epigenetics, Image analysis, Memory, Quantitative microscopy",
author = "{Tom{\'a}s Pereira}, In{\^e}s and Coletta, {Christopher E.} and Perez, {Evelyn V.} and Kim, {David H.} and Michela Gallagher and Goldberg, {Ilya G.} and Rapp, {Peter R.}",
year = "2013",
month = "3",
doi = "10.1016/j.neurobiolaging.2012.07.010",
language = "English (US)",
volume = "34",
pages = "832--844",
journal = "Neurobiology of Aging",
issn = "0197-4580",
publisher = "Elsevier Inc.",
number = "3",

}

TY - JOUR

T1 - CREB-binding protein levels in the rat hippocampus fail to predict chronological or cognitive aging

AU - Tomás Pereira, Inês

AU - Coletta, Christopher E.

AU - Perez, Evelyn V.

AU - Kim, David H.

AU - Gallagher, Michela

AU - Goldberg, Ilya G.

AU - Rapp, Peter R.

PY - 2013/3

Y1 - 2013/3

N2 - Normal cognitive aging is associated with deficits in memory processes dependent on the hippocampus, along with large-scale changes in the hippocampal expression of many genes. Histone acetylation can broadly influence gene expression and has been recently linked to learning and memory. We hypothesized that CREB-binding protein (CBP), a key histone acetyltransferase, may contribute to memory decline in normal aging. Here, we quantified CBP protein levels in the hippocampus of young, aged unimpaired, and aged impaired rats, classified on the basis of spatial memory capacity documented in the Morris water maze. First, CBP-immunofluorescence was quantified across the principal cell layers of the hippocampus using both low and high resolution laser scanning imaging approaches. Second, digital images of CBP immunostaining were analyzed by a multipurpose classifier algorithm with validated sensitivity across many types of input materials. Finally, CBP protein levels in the principal subfields of the hippocampus were quantified by quantitative Western blotting. CBP levels were equivalent as a function of age and cognitive status in all analyses. The sensitivity of the techniques used was substantial, sufficient to reveal differences across the principal cell fields of the hippocampus, and to correctly classify images from young and aged animals independent of CBP immunoreactivity. The results are discussed in the context of recent evidence suggesting that CBP decreases may be most relevant in conditions of aging that, unlike normal cognitive aging, involve significant neuron loss.

AB - Normal cognitive aging is associated with deficits in memory processes dependent on the hippocampus, along with large-scale changes in the hippocampal expression of many genes. Histone acetylation can broadly influence gene expression and has been recently linked to learning and memory. We hypothesized that CREB-binding protein (CBP), a key histone acetyltransferase, may contribute to memory decline in normal aging. Here, we quantified CBP protein levels in the hippocampus of young, aged unimpaired, and aged impaired rats, classified on the basis of spatial memory capacity documented in the Morris water maze. First, CBP-immunofluorescence was quantified across the principal cell layers of the hippocampus using both low and high resolution laser scanning imaging approaches. Second, digital images of CBP immunostaining were analyzed by a multipurpose classifier algorithm with validated sensitivity across many types of input materials. Finally, CBP protein levels in the principal subfields of the hippocampus were quantified by quantitative Western blotting. CBP levels were equivalent as a function of age and cognitive status in all analyses. The sensitivity of the techniques used was substantial, sufficient to reveal differences across the principal cell fields of the hippocampus, and to correctly classify images from young and aged animals independent of CBP immunoreactivity. The results are discussed in the context of recent evidence suggesting that CBP decreases may be most relevant in conditions of aging that, unlike normal cognitive aging, involve significant neuron loss.

KW - Epigenetics

KW - Image analysis

KW - Memory

KW - Quantitative microscopy

UR - http://www.scopus.com/inward/record.url?scp=84870528909&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84870528909&partnerID=8YFLogxK

U2 - 10.1016/j.neurobiolaging.2012.07.010

DO - 10.1016/j.neurobiolaging.2012.07.010

M3 - Article

VL - 34

SP - 832

EP - 844

JO - Neurobiology of Aging

JF - Neurobiology of Aging

SN - 0197-4580

IS - 3

ER -