Evidence for Decreased Nucleolar PARP-1 as an Early Marker of Cognitive Impairment
| Autor: | Alexander Choi, Jiancong Liang, Kavita Verma, Jenny Libien, Matthew J. Regier, A. Iván Hernández |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
medicine.medical_specialty Article Subject Nucleolus Poly (ADP-Ribose) Polymerase-1 Gene Expression Ribosome biogenesis Poly(ADP-ribose) Polymerase Inhibitors Biology Hippocampal formation lcsh:RC321-571 03 medical and health sciences Cognition 0302 clinical medicine Downregulation and upregulation Alzheimer Disease Internal medicine Gene expression medicine Humans Hippocampus (mythology) Cognitive Dysfunction lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Aged 030304 developmental biology Aged 80 and over 0303 health sciences Pyramidal Cells Chromatin Endocrinology Neurology Immunohistochemistry Female Neurology (clinical) Cell Nucleolus 030217 neurology & neurosurgery Research Article |
| Zdroj: | Neural Plasticity, Vol 2019 (2019) Neural Plasticity |
| ISSN: | 1687-5443 2090-5904 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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