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Short-term recognition memory impairment is associated with decreased expression of FK506 binding protein 51 in the aged mouse brain.

Soontornniyomkij V, Risbrough VB, Young JW, Wallace CK, Soontornniyomkij B, Jeste DV, Achim CL - Age (Dordr) (2010)

Bottom Line: Evidence suggests that increased glucocorticoid receptor (GR) signaling may contribute to cognitive decline with age.In aged mice, the frontal cortex FKBP51 IRn correlated directly with DR (r (s) = 0.68, p = 0.002, Spearman rank correlation).These observations suggest that recognition memory impairment in aged mice is associated with decreased FKBP51 expression that may promote GR-mediated glucocorticoid signaling to a greater extent than in unimpaired aged mice.

View Article: PubMed Central - PubMed

Affiliation: Sam and Rose Stein Institute for Research on Aging, University of California, San Diego, La Jolla, CA 92093-0603, USA. vsoontor@ucsd.edu

ABSTRACT
Evidence suggests that increased glucocorticoid receptor (GR) signaling may contribute to cognitive decline with age. We hypothesized that alterations in GR signaling pathway molecules, FK506 binding protein (FKBP) 51 and FKBP52, were associated with memory impairment in aged mice. We used the single-trial object recognition test to measure short-term memory in 18 aged mice compared to 22 young mice, and employed quantitative immunohistochemistry to assess cellular expression of those three proteins in the frontal cortex, hippocampal CA1, and dentate gyrus. Values of the discrimination ratio (DR, a measure of novelty preference) in aged mice were significantly lower than those in young mice (mean 0.54 vs. 0.67, p = 0.003, t test). Aged mice with DR below 0.54 were considered impaired (n = 9). In the three neuroanatomic regions studied, the immunoreactivity normalized to the area measured (IRn) for GR was significantly increased in aged mice regardless of their task performance compared to young mice (p < 0.005), as was the FKBP52 IRn (p < 0.007, U test). In the frontal cortex and CA1, the FKBP51 IRn was significantly lower in impaired aged mice than in unimpaired aged mice (p < 0.01 and <0.05, respectively) and in young mice (p < 0.05 and <0.01, respectively, Dunn's post hoc test). In aged mice, the frontal cortex FKBP51 IRn correlated directly with DR (r (s) = 0.68, p = 0.002, Spearman rank correlation). These observations suggest that recognition memory impairment in aged mice is associated with decreased FKBP51 expression that may promote GR-mediated glucocorticoid signaling to a greater extent than in unimpaired aged mice.

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Scattergraph with its trend line shows significant direct correlation between the immunoreactivity normalized to the neuroanatomic area measured (IRn) in the frontal cortex of aged mice (n = 18) for the FK506 binding protein (FKBP) 51 and the discrimination ratio (i.e., the ratio of the time spent exploring the novel object over the total amount of time spent exploring both familiar and novel objects during the retention phase of the single-trial object recognition test). The p value is two-tailed
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Fig5: Scattergraph with its trend line shows significant direct correlation between the immunoreactivity normalized to the neuroanatomic area measured (IRn) in the frontal cortex of aged mice (n = 18) for the FK506 binding protein (FKBP) 51 and the discrimination ratio (i.e., the ratio of the time spent exploring the novel object over the total amount of time spent exploring both familiar and novel objects during the retention phase of the single-trial object recognition test). The p value is two-tailed

Mentions: In aged mice, the FKBP51 IRn in the frontal cortex (Fig. 5) and CA1 showed significant direct correlation with DR (rs = 0.68 and 0.53, p = 0.002 and 0.024, respectively, Spearman rank correlation). In the dentate gyrus of aged mice, correlation between the FKBP51 IRn and DR did not reach statistical significance (rs = 0.28, p = 0.26, Spearman rank correlation). In young mice, no significant correlation was present between the FKBP51 IRn and DR in any of the three regions studied, i.e., the frontal cortex (rs = −0.16, p = 0.49), CA1 (rs = 0.02, p = 0.93), and dentate gyrus (rs = 0.02, p = 0.99, Spearman rank correlation).Fig. 5


Short-term recognition memory impairment is associated with decreased expression of FK506 binding protein 51 in the aged mouse brain.

Soontornniyomkij V, Risbrough VB, Young JW, Wallace CK, Soontornniyomkij B, Jeste DV, Achim CL - Age (Dordr) (2010)

Scattergraph with its trend line shows significant direct correlation between the immunoreactivity normalized to the neuroanatomic area measured (IRn) in the frontal cortex of aged mice (n = 18) for the FK506 binding protein (FKBP) 51 and the discrimination ratio (i.e., the ratio of the time spent exploring the novel object over the total amount of time spent exploring both familiar and novel objects during the retention phase of the single-trial object recognition test). The p value is two-tailed
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2926850&req=5

Fig5: Scattergraph with its trend line shows significant direct correlation between the immunoreactivity normalized to the neuroanatomic area measured (IRn) in the frontal cortex of aged mice (n = 18) for the FK506 binding protein (FKBP) 51 and the discrimination ratio (i.e., the ratio of the time spent exploring the novel object over the total amount of time spent exploring both familiar and novel objects during the retention phase of the single-trial object recognition test). The p value is two-tailed
Mentions: In aged mice, the FKBP51 IRn in the frontal cortex (Fig. 5) and CA1 showed significant direct correlation with DR (rs = 0.68 and 0.53, p = 0.002 and 0.024, respectively, Spearman rank correlation). In the dentate gyrus of aged mice, correlation between the FKBP51 IRn and DR did not reach statistical significance (rs = 0.28, p = 0.26, Spearman rank correlation). In young mice, no significant correlation was present between the FKBP51 IRn and DR in any of the three regions studied, i.e., the frontal cortex (rs = −0.16, p = 0.49), CA1 (rs = 0.02, p = 0.93), and dentate gyrus (rs = 0.02, p = 0.99, Spearman rank correlation).Fig. 5

Bottom Line: Evidence suggests that increased glucocorticoid receptor (GR) signaling may contribute to cognitive decline with age.In aged mice, the frontal cortex FKBP51 IRn correlated directly with DR (r (s) = 0.68, p = 0.002, Spearman rank correlation).These observations suggest that recognition memory impairment in aged mice is associated with decreased FKBP51 expression that may promote GR-mediated glucocorticoid signaling to a greater extent than in unimpaired aged mice.

View Article: PubMed Central - PubMed

Affiliation: Sam and Rose Stein Institute for Research on Aging, University of California, San Diego, La Jolla, CA 92093-0603, USA. vsoontor@ucsd.edu

ABSTRACT
Evidence suggests that increased glucocorticoid receptor (GR) signaling may contribute to cognitive decline with age. We hypothesized that alterations in GR signaling pathway molecules, FK506 binding protein (FKBP) 51 and FKBP52, were associated with memory impairment in aged mice. We used the single-trial object recognition test to measure short-term memory in 18 aged mice compared to 22 young mice, and employed quantitative immunohistochemistry to assess cellular expression of those three proteins in the frontal cortex, hippocampal CA1, and dentate gyrus. Values of the discrimination ratio (DR, a measure of novelty preference) in aged mice were significantly lower than those in young mice (mean 0.54 vs. 0.67, p = 0.003, t test). Aged mice with DR below 0.54 were considered impaired (n = 9). In the three neuroanatomic regions studied, the immunoreactivity normalized to the area measured (IRn) for GR was significantly increased in aged mice regardless of their task performance compared to young mice (p < 0.005), as was the FKBP52 IRn (p < 0.007, U test). In the frontal cortex and CA1, the FKBP51 IRn was significantly lower in impaired aged mice than in unimpaired aged mice (p < 0.01 and <0.05, respectively) and in young mice (p < 0.05 and <0.01, respectively, Dunn's post hoc test). In aged mice, the frontal cortex FKBP51 IRn correlated directly with DR (r (s) = 0.68, p = 0.002, Spearman rank correlation). These observations suggest that recognition memory impairment in aged mice is associated with decreased FKBP51 expression that may promote GR-mediated glucocorticoid signaling to a greater extent than in unimpaired aged mice.

Show MeSH
Related in: MedlinePlus