Abstract
In order to address pathological cognitive decline effectively, it is critical to adopt early preventive measures in individuals considered at risk. It is therefore essential to develop approaches that identify such individuals before the onset of irreversible dementia. A deficient cholinergic system has been consistently implicated as one of the main factors associated with a heightened vulnerability to the aging process. In the present study we used mice lacking high affinity nicotinic receptors (β2-/-), which have been proposed as an animal model of accelerated/premature cognitive aging. Our aim was to identify behavioral signs that could serve as indicators or predictors of impending cognitive decline. We used test batteries in order to assess cognitive functions and additional tasks to investigate spontaneous behaviors, such as species-specific activities and exploration/locomotion in a novel environment. Our data confirm the hypothesis that β2-/- animals exhibit age-related cognitive impairments in spatial learning. In addition, they document age-related deficits in other areas, such as recognition memory, burrowing and nesting building, thereby extending the validity of this animal model for the study of pathological aging. Finally, our data reveal deficits in spontaneous behavior and habituation processes that precede the onset of cognitive decline and could therefore be useful as a non-invasive behavioral screen for identifying animals at risk. To our knowledge, this is the first study to perform an extensive behavioral assessment of an animal model of premature cognitive aging, and our results suggest that β2-nAChR dependent cognitive deterioration progressively evolves from initial subtle behavioral changes to global dementia due to the combined effect of the neuropathology and aging.
Highlights
Age-related cognitive impairment and dementia are increasingly problematic both for individuals and for societies (Fratiglioni et al, 2000), emphasizing the need for understanding the mechanisms that distinguish normal from pathological aging and designing appropriate therapeutic interventions
Having confirmed a deficit in spatial learning consistent with an accelerated/premature/pathological cognitive aging phenotype, we explored whether other aspects of cognition were affected
Given that activities of daily living (ADL) are often good predictors of cognitive decline in humans (De Vriendt et al, 2015), we examined a variety of species-specific spontaneous behaviors in our experimental groups, including hoarding, marble burying, burrowing, and nesting (Deacon, 2006a,b,c,d)
Summary
Age-related cognitive impairment and dementia are increasingly problematic both for individuals and for societies (Fratiglioni et al, 2000), emphasizing the need for understanding the mechanisms that distinguish normal from pathological aging and designing appropriate therapeutic interventions. The alternative approach is to develop strategies to prevent, or delay age-associated cognitive decline before it becomes settled, thereby increasing the chances to produce longer lasting effects (Galeano et al, 2014; Wisniewski and Drummond, 2015). Such strategies may include pharmacological treatments and changes in diet and lifestyle to modify brain function before the onset of irreversible dementia (Mangialasche et al, 2012). In order to pursue the latter approach it is essential to use animal models that exhibit ageassociated cognitive impairments and examine them earlier in life in order to identify risk factors for pathological cognitive aging
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
