Impact of neuroprotectants on behavioural and cognitive loss in neurodegenerative diseases

Abstract

The discovery of amyloid precursor protein (APP), presenilin 1 (PS1), and presenilin 2 (PS2) mutations associated with hereditary Alzheimer’s disease (AD) was a fundamental step in the development of rodent models to investigate its underlying pathology. This project examined the effects of pre-treatment with photobiomodulation (PBM) or saffron on learning and memory of the APP/PS1 double transgenic mouse using the Intellicage system which allows fully automated continuous testing of behaviour in a home cage environment. Protocols covering exploration, place and place reversal learning, and drinking behaviours were used to characterize longitudinal behaviours. Transgenic mice were successful in learning and re-learning tasks and showed inconsistent effects from both saffron and PBM treatment which may have been influenced by group housing of transgenic and wild-type mice. In contrast when brains were examined by histological analysis at the conclusion of behavioural experiments, it was evident that both PBM and saffron treatment mitigated Aß deposition in the aging APP/PS1 mice. This correlated with reduced mitochondrial dysfunction and saffron pre-treatment also reduced oxidative damage. The mitigation of these three major pathological hallmarks of Alzheimer’s disease – amyloid-ß plaque pathology, oxidative stress and mitochondrial dysfunction, by PBM and saffron treatment reinforces their potential as viable neuroprotective treatments for chronic neurodegenerative conditions. This work emphasises the importance of behavioural testing of animal models in the assessment of treatments and that dietary saffron and PBM are effective, safe, easily administered and minimally invasive interventions to treat chronic neurodegenerative disease.