| First Author | Adebakin A | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 10 | Pages | e45179 |
| PubMed ID | 23056194 | Mgi Jnum | J:192107 |
| Mgi Id | MGI:5464047 | Doi | 10.1371/journal.pone.0045179 |
| Citation | Adebakin A, et al. (2012) Impaired satiation and increased feeding behaviour in the triple-transgenic Alzheimer's disease mouse model. PLoS One 7(10):e45179 |
| abstractText | Alzheimer's disease (AD) is associated with non-cognitive symptoms such as changes in feeding behaviour that are often characterised by an increase in appetite. Increased food intake is observed in several mouse models of AD including the triple transgenic (3xTgAD) mouse, but the mechanisms underlying this hyperphagia are unknown. We therefore examined feeding behaviour in 3xTgAD mice and tested their sensitivity to exogenous and endogenous satiety factors by assessing food intake and activation of key brain regions. In the behavioural satiety sequence (BSS), 3xTgAD mice consumed more food after a fast compared to Non-Tg controls. Feeding and drinking behaviours were increased and rest decreased in 3xTgAD mice, but the overall sequence of behaviours in the BSS was maintained. Exogenous administration of the satiety factor cholecystokinin (CCK; 8-30 microg/kg, i.p.) dose-dependently reduced food intake in Non-Tg controls and increased inactive behaviour, but had no effect on food intake or behaviour in 3xTgAD mice. CCK (15 microg/kg, i.p.) increased c-Fos protein expression in the supraoptic nucleus of the hypothalamus, and the nucleus tractus solitarius (NTS) and area postrema of the brainstem to the same extent in Non-Tg and 3xTgAD mice, but less c-Fos positive cells were detected in the paraventricular hypothalamic nucleus of CCK-treated 3xTgAD compared to Non-Tg mice. In response to a fast or a period of re-feeding, there was no difference in the number of c-Fos-positive cells detected in the arcuate nucleus of the hypothalamus, NTS and area postrema of 3xTgAD compared to Non-Tg mice. The degree of c-Fos expression in the NTS was positively correlated to food intake in Non-Tg mice, however, this relationship was absent in 3xTgAD mice. These data demonstrate that 3xTgAD mice show increased feeding behaviour and insensitivity to satiation, which is possibly due to defective gut-brain signalling in response to endogenous satiety factors released by food ingestion. |
