Evidence for Decreased Nucleolar PARP-1 as an Early Marker of Cognitive Impairment
Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear protein that regulates gene expression through poly(ADP)-ribosylation, resulting in the loosening of chromatin structure. PARP-1 enzymatic activity has been shown to be necessary for the expression of several genes required for memory formation and...
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Neural Plasticity |
| Online Access: | http://dx.doi.org/10.1155/2019/4383258 |
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| author | Matthew Regier Jiancong Liang Alexander Choi Kavita Verma Jenny Libien A. Iván Hernández |
| author_facet | Matthew Regier Jiancong Liang Alexander Choi Kavita Verma Jenny Libien A. Iván Hernández |
| author_sort | Matthew Regier |
| collection | DOAJ |
| description | Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear protein that regulates gene expression through poly(ADP)-ribosylation, resulting in the loosening of chromatin structure. PARP-1 enzymatic activity has been shown to be necessary for the expression of several genes required for memory formation and consolidation. Previously, we showed that nucleolar PARP-1 is significantly decreased in hippocampal pyramidal cells in Alzheimer’s disease (AD). We proposed that the displacement of PARP-1 from the nucleolus results in downregulation of new rRNA expression and ribosome biogenesis, leading to cognitive impairment. To further investigate the relationship between nucleolar PARP-1 and memory impairment, we examined PARP-1 expression in the hippocampi of individuals with mild cognitive impairment (MCI) compared to control and AD cases. We used immunohistochemical techniques to examine the nucleolar distribution of PARP-1 in the Cornu Ammonis (CA region) of the hippocampus. PARP-1 positive cells were then scored for the presence or absence of PARP-1 in the nucleolus. We found a significant decrease of PARP-1 staining in the nucleolar compartment of hippocampal pyramidal cells in MCI compared with Control and AD. When the four CA (CA1-4) regions were considered separately, only the CA1 region showed significant differences in nucleolar PARP-1 with Control > AD > MCI cases. Categorization of nucleolar PARP-1 into “distinct” and “diffuse” groups suggest that most of the changes occur within the distinct group. In addition, measurements of the nucleolar diameter of nucleolar PARP-1 positive cells in CA2 and CA4 showed Control > MCI. Thus, MCI cases had a lower percentage of PARP-1 nucleolar positive cells in CA1 and smaller nucleolar diameters in CA2 and CA4, compared to Control. Our data suggest that disruption of nucleolar form and function is an early and important step in the progression of cognitive impairment. |
| format | Article |
| id | doaj-art-b5bd09356721474885c66e643cb7beaa |
| institution | Kabale University |
| issn | 2090-5904 1687-5443 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Neural Plasticity |
| spelling | doaj-art-b5bd09356721474885c66e643cb7beaa2025-02-03T06:11:22ZengWileyNeural Plasticity2090-59041687-54432019-01-01201910.1155/2019/43832584383258Evidence for Decreased Nucleolar PARP-1 as an Early Marker of Cognitive ImpairmentMatthew Regier0Jiancong Liang1Alexander Choi2Kavita Verma3Jenny Libien4A. Iván Hernández5Department of Pathology, Downstate Medical Center, State University of New York, Brooklyn, NY, USADepartment of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USADepartment of Neurology, Downstate Medical Center, State University of New York, Brooklyn, NY, USADepartment of Pathology, Downstate Medical Center, State University of New York, Brooklyn, NY, USADepartment of Pathology, Downstate Medical Center, State University of New York, Brooklyn, NY, USADepartment of Pathology, Downstate Medical Center, State University of New York, Brooklyn, NY, USAPoly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear protein that regulates gene expression through poly(ADP)-ribosylation, resulting in the loosening of chromatin structure. PARP-1 enzymatic activity has been shown to be necessary for the expression of several genes required for memory formation and consolidation. Previously, we showed that nucleolar PARP-1 is significantly decreased in hippocampal pyramidal cells in Alzheimer’s disease (AD). We proposed that the displacement of PARP-1 from the nucleolus results in downregulation of new rRNA expression and ribosome biogenesis, leading to cognitive impairment. To further investigate the relationship between nucleolar PARP-1 and memory impairment, we examined PARP-1 expression in the hippocampi of individuals with mild cognitive impairment (MCI) compared to control and AD cases. We used immunohistochemical techniques to examine the nucleolar distribution of PARP-1 in the Cornu Ammonis (CA region) of the hippocampus. PARP-1 positive cells were then scored for the presence or absence of PARP-1 in the nucleolus. We found a significant decrease of PARP-1 staining in the nucleolar compartment of hippocampal pyramidal cells in MCI compared with Control and AD. When the four CA (CA1-4) regions were considered separately, only the CA1 region showed significant differences in nucleolar PARP-1 with Control > AD > MCI cases. Categorization of nucleolar PARP-1 into “distinct” and “diffuse” groups suggest that most of the changes occur within the distinct group. In addition, measurements of the nucleolar diameter of nucleolar PARP-1 positive cells in CA2 and CA4 showed Control > MCI. Thus, MCI cases had a lower percentage of PARP-1 nucleolar positive cells in CA1 and smaller nucleolar diameters in CA2 and CA4, compared to Control. Our data suggest that disruption of nucleolar form and function is an early and important step in the progression of cognitive impairment.http://dx.doi.org/10.1155/2019/4383258 |
| spellingShingle | Matthew Regier Jiancong Liang Alexander Choi Kavita Verma Jenny Libien A. Iván Hernández Evidence for Decreased Nucleolar PARP-1 as an Early Marker of Cognitive Impairment Neural Plasticity |
| title | Evidence for Decreased Nucleolar PARP-1 as an Early Marker of Cognitive Impairment |
| title_full | Evidence for Decreased Nucleolar PARP-1 as an Early Marker of Cognitive Impairment |
| title_fullStr | Evidence for Decreased Nucleolar PARP-1 as an Early Marker of Cognitive Impairment |
| title_full_unstemmed | Evidence for Decreased Nucleolar PARP-1 as an Early Marker of Cognitive Impairment |
| title_short | Evidence for Decreased Nucleolar PARP-1 as an Early Marker of Cognitive Impairment |
| title_sort | evidence for decreased nucleolar parp 1 as an early marker of cognitive impairment |
| url | http://dx.doi.org/10.1155/2019/4383258 |
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