Memory interference in APPswe/PS1dE9 mice: Role of astrocytic β‐adrenoreceptors

Abstract

AbstractBackgroundPrevious studies have reported that long‐term β‐adrenoceptor (β‐AR) agonist, isoproterenol hydrochloride (IPE), treatment brings about beneficial effects in an induced model of Alzheimer’s disease (AD) by neutralizing microglial inflammatory morphology against soluble amyloid β oligomers (PMID: 30093491). However, we do not have a clear understanding of how such treatment impacts astrocyte morphology, and whether that afford beneficial effects. Introducing a proactive memory interference step to the classical novel object recognition (NOR) paradigm impairs long‐term memory formation in 2‐month‐old familial model of AD ‐ APPswe/PS1dE9 (APP/PS1) mice. Long‐term IPE treatment rescued long‐term memory. In this study we attempt to understand the impact of long‐term IPE treatment on astrocyte morphology, and how they bring about the reversal in cognitive deficits.Method(1) Mice were taken through a proactive interference step in which they were exposed to objects of varied shape, size and colour before taking them through NOR paradigm. (2) Mice were treated with β‐AR agonist IPE at P26 (0.05g/litre) in drinking water for 21 days till P47. (3) They were sacrificed at 2‐months of age by transcardial perfusion and 100µm coronal sections of hippocampus were stained with astrocytic markers GFAP and S100β by immunohistochemistry. The number and morphology of astrocytes were analysed using ImageJ, SMorph (PMID: 34137444) and Imaris software.ResultOur observations suggest that NOR memory is intact in 2‐month‐old APP/PS1. However, introducing an object‐based short‐term interference before NOR leads to recognition memory deficits in APP/PS1 but not in wild‐type mice. Treatment with IPE restored long‐term memory of APP/PS1 mice to normal levels, thereby protecting them from the effects of interference during the NOR task. Our preliminary findings indicate that IPE impacts the morphology of astrocytes and thus contribute to the reversal of recognition deficits in APP/PS1 at 2 months of age.Conclusionβ‐AR activation can bring about morphological changes in astrocytes that in turn can modulate memory representations.