L1 mouse model of tauopathy shows cholinergic impairment without neuronal degeneration

Identification: Wysocka, Adrianna

L1 mouse model of tauopathy shows cholinergic impairment without neuronal degeneration
A. Wysocka, M. Zadrozny, M. Steczkowska, E. Palasz and G. Niewiadomska
Nencki Institute of Experimental Biology, Warsaw, Poland
The sites of the greatest concentration of tau neurofibrillar tangles in AD are the axons of cholinergic neurons. The aim of this study was to find out whether progression of tauopathy coincides with a functional deterioration in the brain cholinergic system. A transgenic line 1 tau mice (model of Alzheimer's Disease) was used, which expresses truncated tau (amino acids 296-390 of the longest human 441 isoform).
In AD-L1 and wild type NMRI mice at the age of 3 and 9 months the following brain stainings were performed: IHC against repeat domain of tau (7/51 mAb), tau phosphorylated on Ser-404 (p-tau), beta-tubulin, ChAT, p75, VAchT, histochemical staining of AChE activity and Fluoro-Jade C staining.
Tau staining in L1 mice (7/51 mAb) showed the amorphous character of tau immunoreactivity without any signs of tangle-like structures and no change in the level of phosphorylated endogenous tau. However, we observed changed intracellular localization of p-tau in hippocampus and cortex of 9-mo-old L1 mice as compared to NMRI. The greater intensity of cytoplasmic tau immunoreactivity in L1 mice suggests its sequestration from the axodendritic compartment to neuronal somata. Cytoskeleton beta-tubulin staining resembled p-tau. In comparison with control mice in 3- and 9-mo-old L1, there was a decline in anti-ChAT and p75NTR staining, decreased number of ir-cells and atrophy of these cholinergic neurons. We also observed a significantly lower intensity of VAchT and AChE staining in cortex and hippocampus in L1 than in NMRI at both ages. However, we did not detect any neuronal degeneration in hippocampus and cortex with the Fluoro-Jade C staining.
In L1 tauopathic mice there was no degeneration of cholinergic neurons. However, their neurotransmitter phenotype was lost and their projection to hippocampus and cortex was also impaired. This deficiency in cholinergic function may be related to pathological short oligomers of tau present in L1 mice.


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