Anxiety, Impaired Social and Aggressive Behaviour Correlates With Cognitive Decline Accompanied by Molecular Alterations in Older SAMP8 Males

Abstract

Alzheimer’s disease (AD) is characterized by cognitive impairment and different non-cognitive deficits called “Behavioural and psychological symptoms of dementia” (BPSD) related to neurotrophin alterations, which differ from those presented in normal aging. Mouse models, both transgenics and inbreed mice models of AD, are a useful tool in understanding the underlying mechanisms of the disease. The SAMP8 (senescence-accelerated mouse prone 8) mice line was generated from AKR/J strain by Professor Toshio Takeda at the University of Kyoto. This strain exhibited a particular early-onset and accelerated aging phenotype. The present study characterizes and provides information regarding the non-cognitive and cognitive states as well as molecular alterations and their relationship, demonstrating the AD-like symptoms presented in older SAMP8 males. The cognitive impairment presented was accompanied by a reduction in sociability and an increase in aggressive as well as anxiety behaviours. Furthermore, changes in three of the most important neurotrophins, such as NT3, BDNF, and NGF as well as their receptors TrkA and TrkB, were found. Thus, the present results reveal new insights in this useful inbred mouse model of neurodegeneration and AD, demonstrating the potential relationship between neurotrophin alterations, cognitive impairment and neuropsychiatric disorders (ND).

Impact of Brain Endothelial Senescence on Neurogenesis: Application of Novel Strategies for Age-Related Senescence Detection

“…At the age of 7 months, we observed a generalised dysfunction in SAMP8 mice that was accentuated at older ages. Moreover, we identified increased anxious behaviour as a hallmark of functional ageing in this strain, which was also present during natural ageing in C57BL/6 mice, suggesting that anxiety could be a robust indicator of increasing age (Yanai and Endo, 2021;Vasilopoulou et al, 2021). To accurately associate agerelated deficits with an increased senescence burden, we set out to measure global β-Gal levels at this age.…”