Appearance of depression in triple transgenic mouse model of Alzheimer\’s disease
01/30/2020
Dóra Zelena1, 2, Dorottya Várkonyi1, Eszter Sipos1, 1
1 Institute of Experimental Medicine, Hungarian Academy of Science
2 Centre for Neuroscience, Szentágothai Research Centre, Institute of Physiology, Medical School, University of Pécs, Pécs, Hungary
Depression is often co-morbid with Alzheimer\’s disease (AD) contributing to cognitive decline. The triple-transgenic mouse model of AD (3xTg-AD, with human mutated presenilin-1, amyloid precursor and tau protein) shows the typical behavioural dysfunctions, but the timely appearance of its depressive-like co-morbidity symptoms is not well characterized. As the histological hallmarks appear around 6-month, 4- and 8-month-old male mice were compared. A behavioural test battery was used to examine locomotion (openfield, OF), anxiety-like (social interaction, SI), depressive-like (splash test; forced swim, FST) and cognitive (Morris Water Maze, MWM) behaviours. The presence of amyloid plaques were investigated by immunohistochemistry. The 3xTg-AD animals moved less in OF at both age groups, despite normal distanced swam during the MWM suggesting rather motivational, than fitness problem. The 3xTg-AD animals spent more time with grooming during OF in both age groups compared to controls. The duration of friendly social contact during SI test was lower only in 8-month-old 3xTg-AD group as sign of temporal development of anxiety. In splash test, 3xTg-AD mice neglected fur caring as sign of depressive-like behavior, but there was no difference in FST. The latency in finding platform of MWM was higher for 3xTg-AD mice than controls with more robust cognitive decline at 8-month-age. Amyloid plaque was not detected at both age groups. Behavioural tests proved anxiety- and depressive-like changes in some and temporal worsening of the symptoms in few cases. Further early markers of AD should be considered in later studies.