In:
Neuropathology and Applied Neurobiology, Wiley, Vol. 40, No. 7 ( 2014-12), p. 833-843
Abstract:
P 301 S MAPT transgenic mice ( P 301 S mice) are a widely used model of frontotemporal dementia and parkinsonism linked to chromosome 17 with tau pathology ( FTDP ‐17‐tau). However, a systematic correlation between cognitive deficits and cellular tau pathology at different ages is still missing. Therefore, our study investigated memory deficits of P 301 S mice in relation to pathological tau species and dendritic spine pathology throughout adulthood. Methods We analysed P 301 S mice behaviourally with the novel open field, rotarod, and Morris water maze tests to measure deficits in locomotion, balance and cognition, respectively; immunohistochemically with different tau antibodies for specific tau species; and with G olgi staining for dendritic spine pathology. Results We confirmed the occurrence of locomotor deficits at an age of 5 months and newly report memory deficits from 2.5 months of age onwards. At this early age, MC 1 and CP 13, but not AT 180 immunoreactivity, was prominent in the hippocampus of P 301 S mice. Neuronal cell loss in the hippocampus of P 301 S mice was not observed to occur till 6 months of age. However, there was a significant reduction in the density of dendritic spines from young adulthood onwards in hippocampal pyramidal neurones. Conclusion In P 301 S mice, memory deficits precede the onset of locomotor dysfunction and coincide with the appearance of conformationally changed, S 202‐phosphorylated tau and reduced spine density in the absence of neuronal cell loss in the hippocampus. Our finding provides insights into the toxic effects of different tau species in vivo and may facilitate the development of new therapies against neurodegenerative tauopathies.
Type of Medium:
Online Resource
ISSN:
0305-1846
,
1365-2990
DOI:
10.1111/nan.2014.40.issue-7
Language:
English
Publisher:
Wiley
Publication Date:
2014
detail.hit.zdb_id:
2008293-9
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