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Reduced secretagogin expression in the hippocampus of P301L tau transgenic mice


Attems, J; Ittner, A; Jellinger, K; Nitsch, R M; Maj, M; Wagner, L; Götz, J; Heikenwalder, M (2011). Reduced secretagogin expression in the hippocampus of P301L tau transgenic mice. Journal of Neural Transmission, 118(5):737-745.

Abstract

Neuropathological features in Alzheimer's Disease (AD) include the presence of hyperphosphorylated forms of the microtubule-associated tau protein (tau) in hippocampal neurones. Numerous studies indicate a neuroprotective effect of calcium-binding proteins (Ca2+ binding proteins) in neurodegenerative diseases (e.g., AD). Secretagogin is a newly described Ca2+ binding protein that is produced by pyramidal neurones of the human hippocampus. Recently, secretagogin expressing hippocampal neurones were demonstrated to resist tau-induced pathology in AD in contrast to the majority of neighbouring neurones. This suggested a neuroprotective effect of secretagogin in hippocampal neurones. Here, we investigated secretagogin expression in wild type (wt) mice as well as in hemizygous and homozygous P301L tau transgenic (tg) mice, which show pronounced and widespread tau pathology in hippocampal neurones. Secretagogin expression was analyzed at the immunohistochemical and biochemical levels in brains of age-matched wt and hemi- and homozygous tau tg mice. In wt mice hippocampal secretagogin-immunoreactive neurones were invariably detected, while immunoreactivity was much lower (P < 0.001) in tau tg mice. Of note, hippocampal secretagogin immunoreactivity was absent in 62.5% of homozygous tau tg mice. In line with this finding, Western blot analysis demonstrated a significant reduction in protein expression levels of secretagogin in homozygous tau tg compared to wt mice. Our results suggest that increased levels of tau negatively influence secretagogin expression in the hippocampus of tau tg mice.

Neuropathological features in Alzheimer's Disease (AD) include the presence of hyperphosphorylated forms of the microtubule-associated tau protein (tau) in hippocampal neurones. Numerous studies indicate a neuroprotective effect of calcium-binding proteins (Ca2+ binding proteins) in neurodegenerative diseases (e.g., AD). Secretagogin is a newly described Ca2+ binding protein that is produced by pyramidal neurones of the human hippocampus. Recently, secretagogin expressing hippocampal neurones were demonstrated to resist tau-induced pathology in AD in contrast to the majority of neighbouring neurones. This suggested a neuroprotective effect of secretagogin in hippocampal neurones. Here, we investigated secretagogin expression in wild type (wt) mice as well as in hemizygous and homozygous P301L tau transgenic (tg) mice, which show pronounced and widespread tau pathology in hippocampal neurones. Secretagogin expression was analyzed at the immunohistochemical and biochemical levels in brains of age-matched wt and hemi- and homozygous tau tg mice. In wt mice hippocampal secretagogin-immunoreactive neurones were invariably detected, while immunoreactivity was much lower (P < 0.001) in tau tg mice. Of note, hippocampal secretagogin immunoreactivity was absent in 62.5% of homozygous tau tg mice. In line with this finding, Western blot analysis demonstrated a significant reduction in protein expression levels of secretagogin in homozygous tau tg compared to wt mice. Our results suggest that increased levels of tau negatively influence secretagogin expression in the hippocampus of tau tg mice.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Psychiatric University Hospital Zurich > Division of Psychiatric Research and Clinic for Psychogeriatric Medicine
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2011
Deposited On:21 Feb 2012 09:29
Last Modified:05 Apr 2016 15:25
Publisher:Springer
ISSN:0300-9564
Publisher DOI:10.1007/s00702-011-0626-5
PubMed ID:21442354
Permanent URL: http://doi.org/10.5167/uzh-55941

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