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Expression of progerin in aging mouse brains reveals structural nuclear abnormalities without detectible significant alterations in gene expression, hippocampal stem cells or behavior.

Baek JH, Schmidt E, Viceconte N, Strandgren C, Pernold K, Richard TJ, Van Leeuwen FW, Dantuma NP, Damberg P, Hultenby K, Ulfhake B, Mugnaini E, Rozell B, Eriksson M - Hum. Mol. Genet. (2014)

Bottom Line: In addition, low levels of progerin have also been found in several tissues from normal individuals, but it is not clear if low levels of progerin contribute to the aging of the brain.Behavioral analysis and neurogenesis assays, following long-term expression of the HGPS mutation, did not reveal significant pathology.Our results suggest that certain tissues are protected from functional deleterious effects of progerin.

View Article: PubMed Central - PubMed

Affiliation: Department of Biosciences and Nutrition, Center for Innovative Medicine.

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Related in: MedlinePlus

Gene expression and miRNA analyses of different regions of the brain in HGPS and wild-type animals. (A and B) Graphs showing the relative expression of lamin B1 transcript (A) and miR-23a (B) in various regions of the brain from wild-type animals at 3, 83 and 126 weeks of age. (C) Lamin B1 transcript levels in HGPS animals compared with wild-type animals. (D) Western blot showing the expression of mouse lamin A and C in brain, liver, kidney and tail-bone tissues from adult wild-type animals. The sc-6215 antibody was used to detect the lamin A and C proteins. (E) Relative expression level of mouse lamin A and B1 transcripts in various regions of the brain in 20-week-old wild-type animals. (F–H) Relative expression of miR-9 (F), miR-124a (G) and miR-129 (H) in various regions of the brain of 20-week HGPS and wild-type animals. (I) Principal component analysis of the top 1000 genes with the highest average expression levels revealed very small changes in gene expression in the hippocampi of HGPS animals (red) compared with wild-type (blue). Values represent mean ± SEM (*P < 0.05, **P < 0.01–0.001, ***P < 0.001).
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DDU541F5: Gene expression and miRNA analyses of different regions of the brain in HGPS and wild-type animals. (A and B) Graphs showing the relative expression of lamin B1 transcript (A) and miR-23a (B) in various regions of the brain from wild-type animals at 3, 83 and 126 weeks of age. (C) Lamin B1 transcript levels in HGPS animals compared with wild-type animals. (D) Western blot showing the expression of mouse lamin A and C in brain, liver, kidney and tail-bone tissues from adult wild-type animals. The sc-6215 antibody was used to detect the lamin A and C proteins. (E) Relative expression level of mouse lamin A and B1 transcripts in various regions of the brain in 20-week-old wild-type animals. (F–H) Relative expression of miR-9 (F), miR-124a (G) and miR-129 (H) in various regions of the brain of 20-week HGPS and wild-type animals. (I) Principal component analysis of the top 1000 genes with the highest average expression levels revealed very small changes in gene expression in the hippocampi of HGPS animals (red) compared with wild-type (blue). Values represent mean ± SEM (*P < 0.05, **P < 0.01–0.001, ***P < 0.001).

Mentions: Recent studies have suggested that a decrease in lamin B1 levels could serve as a marker for senescence (18–20). However, it has been shown that overexpression of LMNB1 results in abnormal nuclear morphology such as extensive folding, blebbing and lobulation in the nuclear envelope of neuronal cell lines (21). In this study, analysis of lamin B1 expression in different regions of the brain in wild-type animals showed that the level of Lmnb1 transcript decreased significantly in an age-dependent manner, in which the level was lowest at 126 weeks compared with 3 and 87 weeks in all regions of the brain (P = 1.45 × 10−5 for hippocampus, P = 0.0007 for cortex and P = 5 × 10−5 for cerebellum; Fig. 5A). However, there was no difference between 3 and 87 weeks (Fig. 5A). Prior studies have shown that miR-23a targets the LMNB1 gene and regulates lamin B1 expression (20,21). For this reason, miR-23a expression in various regions of the wild-type brain was analyzed at 3, 87 and 126 weeks of age (Fig. 5B). Relative expression levels of miR-23a showed an increasing trend with age. Nevertheless, there was a significant increase in the level of miR-23a in the cortex at 87 weeks (P = 0.002), but this level decreased again by 126 weeks (P = 0.0005), suggesting that there may be regulators other than miR-23a that may govern the expression of lamin B1. Relative Lmnb1 transcript expression was also measured in the brain tissue of 20-week HGPS and wild-type animals. However, there were no significant changes in the level of Lmnb1 transcript in all regions of the brain of HGPS animals compared with wild-type animals (Fig. 5C).Figure 5.


Expression of progerin in aging mouse brains reveals structural nuclear abnormalities without detectible significant alterations in gene expression, hippocampal stem cells or behavior.

Baek JH, Schmidt E, Viceconte N, Strandgren C, Pernold K, Richard TJ, Van Leeuwen FW, Dantuma NP, Damberg P, Hultenby K, Ulfhake B, Mugnaini E, Rozell B, Eriksson M - Hum. Mol. Genet. (2014)

Gene expression and miRNA analyses of different regions of the brain in HGPS and wild-type animals. (A and B) Graphs showing the relative expression of lamin B1 transcript (A) and miR-23a (B) in various regions of the brain from wild-type animals at 3, 83 and 126 weeks of age. (C) Lamin B1 transcript levels in HGPS animals compared with wild-type animals. (D) Western blot showing the expression of mouse lamin A and C in brain, liver, kidney and tail-bone tissues from adult wild-type animals. The sc-6215 antibody was used to detect the lamin A and C proteins. (E) Relative expression level of mouse lamin A and B1 transcripts in various regions of the brain in 20-week-old wild-type animals. (F–H) Relative expression of miR-9 (F), miR-124a (G) and miR-129 (H) in various regions of the brain of 20-week HGPS and wild-type animals. (I) Principal component analysis of the top 1000 genes with the highest average expression levels revealed very small changes in gene expression in the hippocampi of HGPS animals (red) compared with wild-type (blue). Values represent mean ± SEM (*P < 0.05, **P < 0.01–0.001, ***P < 0.001).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4321440&req=5

DDU541F5: Gene expression and miRNA analyses of different regions of the brain in HGPS and wild-type animals. (A and B) Graphs showing the relative expression of lamin B1 transcript (A) and miR-23a (B) in various regions of the brain from wild-type animals at 3, 83 and 126 weeks of age. (C) Lamin B1 transcript levels in HGPS animals compared with wild-type animals. (D) Western blot showing the expression of mouse lamin A and C in brain, liver, kidney and tail-bone tissues from adult wild-type animals. The sc-6215 antibody was used to detect the lamin A and C proteins. (E) Relative expression level of mouse lamin A and B1 transcripts in various regions of the brain in 20-week-old wild-type animals. (F–H) Relative expression of miR-9 (F), miR-124a (G) and miR-129 (H) in various regions of the brain of 20-week HGPS and wild-type animals. (I) Principal component analysis of the top 1000 genes with the highest average expression levels revealed very small changes in gene expression in the hippocampi of HGPS animals (red) compared with wild-type (blue). Values represent mean ± SEM (*P < 0.05, **P < 0.01–0.001, ***P < 0.001).
Mentions: Recent studies have suggested that a decrease in lamin B1 levels could serve as a marker for senescence (18–20). However, it has been shown that overexpression of LMNB1 results in abnormal nuclear morphology such as extensive folding, blebbing and lobulation in the nuclear envelope of neuronal cell lines (21). In this study, analysis of lamin B1 expression in different regions of the brain in wild-type animals showed that the level of Lmnb1 transcript decreased significantly in an age-dependent manner, in which the level was lowest at 126 weeks compared with 3 and 87 weeks in all regions of the brain (P = 1.45 × 10−5 for hippocampus, P = 0.0007 for cortex and P = 5 × 10−5 for cerebellum; Fig. 5A). However, there was no difference between 3 and 87 weeks (Fig. 5A). Prior studies have shown that miR-23a targets the LMNB1 gene and regulates lamin B1 expression (20,21). For this reason, miR-23a expression in various regions of the wild-type brain was analyzed at 3, 87 and 126 weeks of age (Fig. 5B). Relative expression levels of miR-23a showed an increasing trend with age. Nevertheless, there was a significant increase in the level of miR-23a in the cortex at 87 weeks (P = 0.002), but this level decreased again by 126 weeks (P = 0.0005), suggesting that there may be regulators other than miR-23a that may govern the expression of lamin B1. Relative Lmnb1 transcript expression was also measured in the brain tissue of 20-week HGPS and wild-type animals. However, there were no significant changes in the level of Lmnb1 transcript in all regions of the brain of HGPS animals compared with wild-type animals (Fig. 5C).Figure 5.

Bottom Line: In addition, low levels of progerin have also been found in several tissues from normal individuals, but it is not clear if low levels of progerin contribute to the aging of the brain.Behavioral analysis and neurogenesis assays, following long-term expression of the HGPS mutation, did not reveal significant pathology.Our results suggest that certain tissues are protected from functional deleterious effects of progerin.

View Article: PubMed Central - PubMed

Affiliation: Department of Biosciences and Nutrition, Center for Innovative Medicine.

Show MeSH
Related in: MedlinePlus