Analysis of ribosomal protein S6 baseline phosphorylation and effect of tau pathology in the murine brain and human hippocampus
| Autor: | Christoph Köhler, Maja Dinekov, Maria Klingebiel |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male Pathology medicine.medical_specialty Transgene Fluorescent Antibody Technique Mice Transgenic tau Proteins Biology 03 medical and health sciences 0302 clinical medicine Alzheimer Disease medicine Hippocampus (mythology) Animals Humans Eukaryotic Small Ribosomal Subunit Phosphorylation Molecular Biology PI3K/AKT/mTOR pathway Aged Aged 80 and over Neurons Ribosomal Protein S6 General Neuroscience TOR Serine-Threonine Kinases Autophagy Brain medicine.disease Cell biology Mice Inbred C57BL 030104 developmental biology Ribosomal protein s6 Female Neurology (clinical) Tauopathy 030217 neurology & neurosurgery Developmental Biology Signal Transduction |
| Zdroj: | Brain research. 1659 |
| ISSN: | 1872-6240 |
| Popis: | We examined the distribution pattern of the phosphorylated 40S ribosomal subunit protein S6, a downstream target of the mTOR pathway, in the brains of 24-months-old human tau transgenic pR5 mice, non-transgenic littermates and in human hippocampi. We studied baseline levels of phosphorylated S6 and a possible effect of tau pathology. S6 phosphorylated at Ser235/236 (pS6Ser235/236) or Ser240/244 (pS6Ser240/244) has been used as a read-out of mTOR activity in several studies. The mTOR pathway regulates a wide variety of cellular functions including cell growth, ribosome biosynthesis, translational control and autophagy. Its dysregulation might underlie the neurodegenerative pathology of Alzheimer's disease and other tauopathies. pS6Ser235/236 and pS6Ser240/244 immunoreactivity in the mouse brain were widespread and similar distributed, but intensive pS6Ser235/236 immunoreactivity was more selective, especially highlighting certain brainstem regions. In the human hippocampus mainly granulovacuolar inclusions in neurons displayed pS6Ser235/236 immunoreactivity. In contrast, a considerable number of neurons displayed pS6Ser240/244 immunoreactivity in the cytoplasm without labeling of granulovacuolar inclusions. Except for a tendency of lower numbers of intensely phosphorylated S6-positive neurons in pR5 mice, the pattern of distribution of pS6Ser235/236 and pS6Ser240/244 immunoreactivity was largely unchanged when compared with non-transgenic mice and also when human hippocampi from AD cases and controls were compared. Similar to pR5 mice most neurons with hyper-phosphorylated tau in human hippocampi displayed no or only weak labeling for phosphorylated S6, suggesting that phosphorylated S6 is not especially associated with pathological tau, but is rather a feature of unaffected neurons. |
| Databáze: | OpenAIRE |
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