Universität zu Köln

Klingebiel, Maria, Dinekov, Maja and Koehler, Christoph (2017). Analysis of ribosomal protein S6 baseline phosphorylation and effect of tau pathology in the murine brain and human hippocampus. Brain Res., 1659. S. 121 - 136. AMSTERDAM: ELSEVIER SCIENCE BV. ISSN 1872-6240

Full text not available from this repository.

Abstract

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. (C) 2017 Elsevier B.V. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Klingebiel, Maria UNSPECIFIED UNSPECIFIED UNSPECIFIED Dinekov, Maja UNSPECIFIED UNSPECIFIED UNSPECIFIED Koehler, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-236588
DOI:	10.1016/j.brainres.2017.01.016
Journal or Publication Title:	Brain Res.
Volume:	1659
Page Range:	S. 121 - 136
Date:	2017
Publisher:	ELSEVIER SCIENCE BV
Place of Publication:	AMSTERDAM
ISSN:	1872-6240
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language TOP MESSENGER-RNAS; MAMMALIAN TARGET; ALZHEIMERS-DISEASE; GRANULOVACUOLAR DEGENERATION; TRANSLATIONAL CONTROL; SYNAPTIC PLASTICITY; SIGNALING PATHWAY; FEAR MEMORY; MOUSE MODEL; CELL-SIZE Multiple languages Neurosciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/23658