Maximal COX-2 and ppRb expression in neurons occurs during early Braak stages prior to the maximal activation of astrocytes and microglia in Alzheimer's disease
<p>Abstract</p> <p>Neuronal expression of cyclooxygenase-2 (COX-2) and cell cycle proteins is suggested to contribute to neurodegeneration during Alzheimer's disease (AD). The stimulus that induces COX-2 and cell cycle protein expression in AD is still elusive. Activated glia...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2005-11-01
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| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | http://www.jneuroinflammation.com/content/2/1/27 |
| _version_ | 1818143700003323904 |
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| author | Arendt Thomas Veerhuis Robert van Haastert Elise S Hoozemans Jeroen JM Scheper Wiep Eikelenboom Piet Rozemuller Annemieke JM |
| author_facet | Arendt Thomas Veerhuis Robert van Haastert Elise S Hoozemans Jeroen JM Scheper Wiep Eikelenboom Piet Rozemuller Annemieke JM |
| author_sort | Arendt Thomas |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Neuronal expression of cyclooxygenase-2 (COX-2) and cell cycle proteins is suggested to contribute to neurodegeneration during Alzheimer's disease (AD). The stimulus that induces COX-2 and cell cycle protein expression in AD is still elusive. Activated glia cells are shown to secrete substances that can induce expression of COX-2 and cell cycle proteins <it>in vitro</it>. Using <it>post mortem </it>brain tissue we have investigated whether activation of microglia and astrocytes in AD brain can be correlated with the expression of COX-2 and phosphorylated retinoblastoma protein (ppRb). The highest levels of neuronal COX-2 and ppRb immunoreactivity are observed in the first stages of AD pathology (Braak 0–II, Braak A). No significant difference in COX-2 or ppRb neuronal immunoreactivity is observed between Braak stage 0 and later Braak stages for neurofibrillary changes or amyloid plaques. The mean number of COX-2 or ppRb immunoreactive neurons is significantly decreased in Braak stage C compared to Braak stage A for amyloid deposits. Immunoreactivity for glial markers KP1, CR3/43 and GFAP appears in the later Braak stages and is significantly increased in Braak stage V-VI compared to Braak stage 0 for neurofibrillary changes. In addition, a significant negative correlation is observed between the presence of KP1, CR3/43 and GFAP immunoreactivity and the presence of neuronal immunoreactivity for COX-2 and ppRb. These data show that maximal COX-2 and ppRb immunoreactivity in neurons occurs during early Braak stages prior to the maximal activation of astrocytes and microglia. In contrast to <it>in vitro </it>studies, <it>post mortem </it>data do not support a causal relation between the activation of microglia and astrocytes and the expression of neuronal COX-2 and ppRb in the pathological cascade of AD.</p> |
| first_indexed | 2024-12-11T11:35:50Z |
| format | Article |
| id | doaj.art-221cb4d89d7e4a11906ebf5f53d0e702 |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-12-11T11:35:50Z |
| publishDate | 2005-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-221cb4d89d7e4a11906ebf5f53d0e7022022-12-22T01:08:45ZengBMCJournal of Neuroinflammation1742-20942005-11-01212710.1186/1742-2094-2-27Maximal COX-2 and ppRb expression in neurons occurs during early Braak stages prior to the maximal activation of astrocytes and microglia in Alzheimer's diseaseArendt ThomasVeerhuis Robertvan Haastert Elise SHoozemans Jeroen JMScheper WiepEikelenboom PietRozemuller Annemieke JM<p>Abstract</p> <p>Neuronal expression of cyclooxygenase-2 (COX-2) and cell cycle proteins is suggested to contribute to neurodegeneration during Alzheimer's disease (AD). The stimulus that induces COX-2 and cell cycle protein expression in AD is still elusive. Activated glia cells are shown to secrete substances that can induce expression of COX-2 and cell cycle proteins <it>in vitro</it>. Using <it>post mortem </it>brain tissue we have investigated whether activation of microglia and astrocytes in AD brain can be correlated with the expression of COX-2 and phosphorylated retinoblastoma protein (ppRb). The highest levels of neuronal COX-2 and ppRb immunoreactivity are observed in the first stages of AD pathology (Braak 0–II, Braak A). No significant difference in COX-2 or ppRb neuronal immunoreactivity is observed between Braak stage 0 and later Braak stages for neurofibrillary changes or amyloid plaques. The mean number of COX-2 or ppRb immunoreactive neurons is significantly decreased in Braak stage C compared to Braak stage A for amyloid deposits. Immunoreactivity for glial markers KP1, CR3/43 and GFAP appears in the later Braak stages and is significantly increased in Braak stage V-VI compared to Braak stage 0 for neurofibrillary changes. In addition, a significant negative correlation is observed between the presence of KP1, CR3/43 and GFAP immunoreactivity and the presence of neuronal immunoreactivity for COX-2 and ppRb. These data show that maximal COX-2 and ppRb immunoreactivity in neurons occurs during early Braak stages prior to the maximal activation of astrocytes and microglia. In contrast to <it>in vitro </it>studies, <it>post mortem </it>data do not support a causal relation between the activation of microglia and astrocytes and the expression of neuronal COX-2 and ppRb in the pathological cascade of AD.</p>http://www.jneuroinflammation.com/content/2/1/27Alzheimer's diseaseastrocytescell cyclecyclooxygenase-2microgliaretinoblastoma protein |
| spellingShingle | Arendt Thomas Veerhuis Robert van Haastert Elise S Hoozemans Jeroen JM Scheper Wiep Eikelenboom Piet Rozemuller Annemieke JM Maximal COX-2 and ppRb expression in neurons occurs during early Braak stages prior to the maximal activation of astrocytes and microglia in Alzheimer's disease Journal of Neuroinflammation Alzheimer's disease astrocytes cell cycle cyclooxygenase-2 microglia retinoblastoma protein |
| title | Maximal COX-2 and ppRb expression in neurons occurs during early Braak stages prior to the maximal activation of astrocytes and microglia in Alzheimer's disease |
| title_full | Maximal COX-2 and ppRb expression in neurons occurs during early Braak stages prior to the maximal activation of astrocytes and microglia in Alzheimer's disease |
| title_fullStr | Maximal COX-2 and ppRb expression in neurons occurs during early Braak stages prior to the maximal activation of astrocytes and microglia in Alzheimer's disease |
| title_full_unstemmed | Maximal COX-2 and ppRb expression in neurons occurs during early Braak stages prior to the maximal activation of astrocytes and microglia in Alzheimer's disease |
| title_short | Maximal COX-2 and ppRb expression in neurons occurs during early Braak stages prior to the maximal activation of astrocytes and microglia in Alzheimer's disease |
| title_sort | maximal cox 2 and pprb expression in neurons occurs during early braak stages prior to the maximal activation of astrocytes and microglia in alzheimer s disease |
| topic | Alzheimer's disease astrocytes cell cycle cyclooxygenase-2 microglia retinoblastoma protein |
| url | http://www.jneuroinflammation.com/content/2/1/27 |
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