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P1‐190: Acceleration of aging‐dependent changes in adult neural stem cell populations in the 3XTg mouse model of Alzheimer's disease
Author(s) -
Hamilton Laura K.,
Aumont Anne,
Julien Carl,
Vadnais Alexandra,
Calon Frédéric,
Fernandes Karl J.L.
Publication year - 2010
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.2010.05.740
Subject(s) - neurogenesis , dentate gyrus , neural stem cell , subventricular zone , subgranular zone , neuroscience , neuroblast , doublecortin , hippocampal formation , biology , stem cell , lateral ventricles , hippocampus , granule cell , forebrain , central nervous system , microbiology and biotechnology
neurotransmitter in learning and memory processes. Alterations in 5-HT neurotransmission have been recently implicated in AD, however, it is not clear how hippocampal 5-HT innervation is modified. Methods: We studied the hippocampal 5-HT input by analyzing (i) the expression, density and distribution of serotonin transporter immunoreactive fibres (SERT-IRF); (ii) the specific morphological characteristics of serotonergic fibres and their relation to amyloid plaques; (iii) the distribution and synaptic connectivity of serotonergic terminals and unmyelinated axons (SERT-Te/Ax) and (iv) the total number of serotonin neurones within the raphe nuclei in the triple transgenic mouse model of Alzheimer’s disease (3xTg-AD). We used quantitative light and electron microscopy immunohistochemistry to analyze the differences between 3xTg-AD and non-transgenic animals (non-Tg) at different ages (3, 6, 9, 12 and 18 months). Results: 3xTg-AD showed a significant increase in SERT-IRF density in the hippocampus in a subfield, strata and age specific manner. The increase in SERT-IRF was specific to the CA1 stratum lacunosum moleculare. Increase in SERT-IRF in 3xTg-AD was observed at 3 months (61%) and at 18 months (74%) when compared to non-Tg. Increased SERT-IRF density was more pronounced adjacent to amyloid plaques. Ultrastructural studies also revealed that the 3xTg-AD animals have an specific concomitant increase of SERT-Te/Ax in the CA1. This Increase in SERTTe/Ax in transgenic animals was observed also at 3 months (146 %) and at 18 months (153 %) of non-Tg values. In addition, SERTTe/Ax had a significant increased surface area these ages (67% and 50% respectively). However, no changes were found in the total number of raphe serotonin neurones at any age. Conclusions: Our results indicate that triple transgenic mice display increased SERT-IRF sprouting and increased SERT-Te density which may account for imbalanced serotonergic neurotransmission associated with Alzheimer’s disease cognitive impairment.