Social isolation (SI) predicts morbidity and mortality in a multitude of diseases, including cancer and cardiovascular disease. Patients with high levels of social support or large social networks have lower risks of developing neurodegenerative diseases such as Alzheimer's Disease (AD) and progress more slowly once diagnosed. Whether this is also true in other amyloid related diseases such as the increasingly common disorder of cerebral amyloid angiopathy (CAA), is not known. Social interaction overcomes the detrimental effects of SI by promoting adaptive behaviors and favorable neuroendocrine responses to biological stressors. We hypothesize that social interaction will reduce inflammation, enhance amyloid clearance/phagocytosis, and increase microRNA that regulate neurotrophins such as BDNF. Despite the huge impact of SI on human disease, no study has attempted to mitigate the detrimental effects of isolation on neurobehavioral outcomes using target-based approaches. MicroRNAs (miRNAs) are short non-coding RNAs that are emerging as a powerful intervention tool for many diseases including Alzheimer's Disease (AD). They regulate a broad spectrum of biological pathways through fine-tuning of protein expression levels and altering gene expression levels. They have the ability to concurrently target multiple effectors of pathways involved in disease pathology. Very recent studies have found that microRNAs mediate many aspects of social interaction, leading us to hypothesize that miRNA regulation is involved in the detrimental effects of social isolation in neurodegenerative diseases. In this supplement we will determine which miRNAs are differentially expressed in in a mouse model of CAA during social isolation. Both male and female mice will be used. The overall goal of this proposal is to determine if social isolation reduces the time to symptom onset or enhances the progression of cerebral amyloid angiopathy by effects on microRNA expression.
Social factors have a profound effect on health; loneliness and social isolation are recognized as important contributors to morbidity and mortality from many diseases, including neurodegenerative diseases. Cerebral amyloid angiopathy (CAA) is an increasingly prevalent neurodegenerative disease in which amyloid is deposited in the walls of the brain's blood vessels, leading to white matter degeneration, intracerebral hemorrhage, and cognitive decline. The work in this supplement will determine if social isolation influences the onset and progression of disease in a mouse model of CAA in the hope of identifying targetable pathways that can be developed for human use.
|Verma, Rajkumar; Ritzel, Rodney M; Harris, Nia M et al. (2018) Inhibition of miR-141-3p Ameliorates the Negative Effects of Poststroke Social Isolation in Aged Mice. Stroke 49:1701-1707|