Abstract
Alzheimer's disease (AD) is a progressive neurodegenerative disease that deteriorates cognitive functions and associated brain regions such as the hippocampus. Serotonin (5-HT) widely distributed throughout the hippocampus, is a key neurotransmitter in learning and memory processes. Alterations in 5-HT neurotransmission have been implicated in AD, however, it is not clear how hippocampal 5-HT innervation is modified. Here, 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 SERT-IRF 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 5-HT neurons 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 study 3xTg-AD and non-transgenic animals (non-Tg) at different ages (3, 6, 9, 12 and 18 months). 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%) compared to non-Tg controls. Increased SERT-IRF density was more pronounced adjacent to amyloid plaques. Ultrastructural studies also revealed that the 3xTg-AD animals have a specific concomitant increase of SERT-Te/Ax in the CA1 at these ages (146% and 153% respectively). However, no changes were found in the total number of raphe serotonin neurons at any age. 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.
| Original language | English |
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| Publication status | Published - 5 Jul 2010 |
| Event | 7th FENS Forum of European Neuroscience - Amsterdam, The Netherland Duration: 3 Jul 2010 → 7 Jul 2010 |
Conference
| Conference | 7th FENS Forum of European Neuroscience |
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| City | Amsterdam, The Netherland |
| Period | 3/07/10 → 7/07/10 |