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[P1–197]: CHARACTERISING THE CHOLINERGIC PHENOTYPES IN TRANSGENIC MODELS FOR ALZHEIMER's DISEASE AND FRONTOTEMPORAL LOBAR DEGENERATION BY CHAT, P75 NTR , P‐TRKA AND NGF PROTEINS STAINING
Author(s) -
Wysocka Adrianna,
Zadrozny Maciej,
Hyatt James,
Steczkowska Marta,
Palasz Ewelina,
Folcik Radoslaw,
Niewiadomska Grazyna
Publication year - 2017
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2017.06.017
Subject(s) - basal forebrain , cholinergic neuron , cholinergic , choline acetyltransferase , tropomyosin receptor kinase a , tauopathy , neuroscience , low affinity nerve growth factor receptor , neurotrophin , frontotemporal lobar degeneration , biology , hippocampus , alzheimer's disease , nerve growth factor , medicine , endocrinology , receptor , frontotemporal dementia , neurodegeneration , disease , dementia
Background: Alzheimer’s disease (AD) is associated with severe loss of cholinergic markers in the brain, and such loss may be due to the toxic interaction of tau with muscarinic receptors. So far, significance of tau signaling through muscarinic receptor in solely in vivo tauopathic models remains uncertain. Methods: In this study, we evaluated cholinergic neurons morphology in two tauopathic mouse models: Line 1 (L1), with mild AD-like tauopathy and Line 66 (L66) with severe frontotemporal lobar degeneration-like tauopathy (FTLD), and wild-type mice as controls (Melis et al. 2015). Analysis was performed in 3-(young), 6-(aging) and 9month-old (aged) mice. Immunohistochemical staining against cholinergic markers ChAT, p75, p-TrkA and NGF, as well as ELISA for NGF in cortex and hippocampus were performed. Results: We found that ChAT and p75 immunostainings were decreased in the basal forebrain cholinergic neurons only in L1. Decreased number of immunopositive cells and atrophic changes in cholinergic neurons morphology of L1 mice were observed in 3-mo-old animals before tauopathic symptoms developed. Alterations of the normal cholinergic phenotypewere observed in striatal interneurons, as well as in projective neurons of medial septum, horizontal and vertical limbs of diagonal band and in magnocellular basal nucleus. Changes in cholinergic neurons number and morphology were not observed in L66. NGF level reduction was the largest in line L1, what corresponds with the changes in intensity of stainings against p-TrkA and p75 in most structures by the age of 3 months. Conclusions:Morphological changes in cholinergic system in line L1 correspond to those observed in AD. In opposite, the lack of changes in cholinergic system in line L66 is compatible with the data that there is no cholinergic deficit in FTLD patients and in animal models of the disease. Phenotype impairment of cholinergic neurons may be related to the type of pathological forms of tau protein short oligomers or low aggregated forms such as PHF in L1, in contrast to the highly aggregated strands of NFTtype in L66, forming in brain due to the use of different tau constructs during transgenisation. Sponsored by NCN UMO-2014/15/B/NZ4/05041 grant and WisTa Laboratories Ltd.