Neuronal and behavioural effects of social isolation in old age

Abstract

Social isolation in humans is marked by fewer quality social relationships and is agravated after retirement, widowhood and the loss of close friends. Thus, social isolation is particularly prevalent in elderly people and is becoming an increasing problem in countries with a longer average lifespan. At present, there is epidemiological evidence indicating that social isolation is a risk factor for the development of various diseases such as cardiovascular disorders, depression, cognitive decline and even increased mortality. While many animal studies have investigated the eff ects of social isolation during the pre-weaning and juvenile period on behavior, only a few studies have investigated the behavioural and cognitive consequences of social isolation in adulthood or in old age. The main hypothesis of this work is that social isolation can be considered a stressful situation that, when occurs at late adulthood or in old age, induces changes in certain physiological and neurobiological processes aff ecting behavior and exacerbating agerelated cognitive decline. In the first part of this study we used adult female Octodon degus to investigate the effects of long-term social isolation on contextual and cued fear conditioning, and the possible modulation of the synaptic levels of NCAM and PSA-NCAM in the hippocampus. After 6½ months of social isolation, adult female degus showed a normal auditory-cued fear memory, but a deficit in contextual fear memory, a hippocampal dependent task. Subsequently, we observed reduced hippocampal synaptic levels of PSA-NCAM in isolated compared to grouped-housed female degus. Interestingly, social isolation reduced the volume of the hippocampal CA1 subfield, without aff ecting the volume of the CA3 subregion or the total hippocampus. Moreover, attenuated body weight gain and reduced number of granulocytes were detected in isolated animals. Our findings indicate for the first time, that long-term social isolation of adult female animals induces a specific shrinkage of CA1 and a decrease in synaptic levels of PSA-NCAM in the hippocampus. These effects may be related to the deficit in contextual fear memory observed in isolated female degus. Our studies with male Wistar rats, carried out in the second part of the study, indicate that social isolation at aging progressively alters sympathetic activity, and increases anxiety and depressive- like behaviour. In addition, long-term isolated rats showed elevated plasmatic corticosterone levels and displayed morphological, electrophysiological and biochemical changes in the hippocampus that may lead to the spatial memory impairment observed in these animals. After long term social isolation, systemic administration of a synthetic peptide that mimics some neural cell adhesion activities was able to revert isolation-induced spatial memory impairment, indicating that this pharmacological treatment may be of therapeutic relevance.