Olfactory Signatures in the Food Finding Test in Mice With Normal and Alzheimer’s Disease-Pathological Aging With Special Concerns on the Effects of Social Isolation

Abstract

The temporal course and the severity of the involution of sensory systems through aging can be critical since they ensure the ability to perceive and recognize the world. In older people, sensory impairments significantly increase their risk of biological, psychological, and social impoverishment. Besides this, olfactory loss is considered an early biomarker in Alzheimer’s disease (AD) neurodegenerative process. Here we studied olfactory ethograms in middle-aged male and female gold-standard C57BL/6 mice and 3xTg-AD mice, a genetic model of AD that presents cognitive dysfunction and a conspicuous neuropsychiatric-like phenotype. A paradigm involving 1-day food deprivation was used to investigate the ethological patterns shown in the olfactory inspection of a new cage and the sniffing, finding, and eating of hidden food pellets. The sniffing–find–eat temporal patterns were independent of the loss of weight and unveiled (fast) olfactory signatures in Alzheimer’s disease, differing from those (slow progressive) in normal aging. Male 3xTg-AD mice exhibited an early signature than female mice, opposite to animals with normal aging. The sequence of actions was correlated in male and female 3xTg-AD mice in contrast to control mice. Social isolation, naturally occurring in male 3xTg-AD due to the death of cage mates, emphasized their olfactory patterns and disrupted the behavioral correlates. The paradigm provided distinct contextual, sex, and genotype olfactory ethogram signatures useful to investigate olfactory function in normal and AD-pathological aging. Isolation had an impact on enhancing the changes in the olfactory signature here described, for the first time, in the 3xTg-AD model of Alzheimer’s disease.

Crosstalk of Alzheimer’s disease-phenotype, HPA axis, splenic oxidative stress and frailty in late-stages of dementia, with special concerns on the effects of social isolation: A translational neuroscience approach

“…Thus, like in humans ( Gerst-Emerson and Jayawardhana, 2015 ), housing/social conditions can significantly impact animal behavior, morbidity, and mortality outcomes. However, only a few laboratories have studied the effects of poor social housing in AD models, despite reporting worsened cognition and neuropathology ( Pietropaolo et al, 2009 ; Huang et al, 2015 ; Muntsant and Giménez-Llort, 2020 ; Peterman et al, 2020 ), enhancement of olfactory patterns ( Marín-Pardo and Giménez-Llort, 2021 ), body and organs weight loss, and increased asymmetric atrophy of the hippocampus ( Muntsant and Giménez-Llort, 2020 ). Interestingly, the present work shows that even short isolation could increase the activity in 3xTg-AD mice and counteract the low activity levels associated with the AD-genotype.…”

Temporal Appearance of Enhanced Innate Anxiety in Alzheimer Model Mice

“…However, sixmonth-old 3xTg-AD mice did not show olfactory deficit to social and non-social (almond and banana) odors [37]. The outcome of experiments evaluating olfaction by finding buried food [35,38] can be deeply confounded by metabolic/motivational processes, known to be altered in the 3xTg-AD mice [39]. In another case, sex-related olfactory function was measured, which can be influenced by sexual drive [36].…”

Electroacupuncture ameliorates cerebrovascular impairment in Alzheimer's disease mice via melatonin signaling

“… 37 , 50 Thus, our results further suggested more vascular network is to be mature and engaged in blood circulation after 8‐weeks EAST36 treatment. Considering that olfactory dysfunction and neuropsychiatric symptoms mutually interact with AD progression and precede the vast neurodegeneration in the brain, 27 , 51 , 52 , 53 treatment of olfactory dysfunction and neuropsychiatric symptoms is not only the issue of life quality improvement for the patient but also the intervention of AD progression. Excitedly, our data suggested that EAST36 treatment worked in this position by relieving early neurological symptoms and Aβ accumulation in cerebral vessels in AD mice, greatly downregulating the risks of progressive cognitive decline in AD.…”

“…Food‐finding test, 27 elevated‐plus maze (EPM), 28 and Morris‐water maze test 29 were applied to assess the olfactory symptoms, anxiety‐like symptoms, and cognitive deficit in mice, respectively. The detailed performance was described in the Appendix S1 .…”