Effects of long-term social isolation on central, behavioural and metabolic parameters in middle-aged mice.

Social isolation gained discussion momentum due to the COVID-19 pandemic. Whereas many studies address the effects of long-term social isolation in post-weaning and adolescence and for periods ranging from 4 to 12 weeks, little is known about the repercussions of adult long-term social isolation in middle age. Thus, our aim was to investigate how long-term social isolation can influence metabolic, behavioural, and central nervous system-related areas in middle-aged mice. Adult male C57Bl/6 mice (4 months-old) were randomly divided into Social (2 cages, n = 5/cage) and Isolated (10 cages, n = 1/cage) housing groups, totalizing 30 weeks of social isolation, which ended concomitantly with the onset of middle age of mice. At the end of the trial, metabolic parameters, short-term memory, anxiety-like behaviour, and physical activity were assessed. Immunohistochemistry in the hippocampus (ΔFosB, BDNF, and 8OHDG) and hypothalamus (ΔFosB) was also performed. The Isolated group showed impaired memory along with a decrease in hippocampal ΔFosB at dentate gyrus and in BDNF at CA3. Food intake was also affected, but the direction depended on how it was measured in the Social group (individually or in the group) with no alteration in ΔFosB at the hypothalamus. Physical activity parameters increased with chronic isolation, but in the light cycle (inactive phase), with some evidence of anxiety-like behaviour. Future studies should better explore the timepoint at which the alterations found begin. In conclusion, long-term social isolation in adult mice contributes to alterations in feeding, physical activity pattern, and anxiety-like behaviour. Moreover, short-term memory deficit was associated with lower levels of hippocampal ΔFosB and BDNF in middle age.

COVID-19 in age-related neurodegenerative diseases: is there a role for vitamin D3 as a possible therapeutic strategy?

The coronavirus disease (COVID-19), identified in Wuhan, China, on December 2019, was declared a pandemic by the World Health Organization, on March, 2020. Since then, efforts have been gathered to describe its clinical course and to determine preventive measures and treatment strategies. Adults older than 65 years of age are more susceptible to serious clinical symptoms and present higher mortality rates. Angiotensin-converting enzyme 2 (ACE2) is a major receptor for some coronavirus infection, including SARS-COV-2, but is also a crucial determinant in anti-inflammation processes during the renin-angiotensin system (RAS) functioning - converting angiotensin II to angiotensin 1-7. The decline in ACE2 expression that occurs with aging has been associated to the higher morbidity and mortality rates in older adults. These observations highlight the importance of investigating the association between COVID-19 and age-related neurodegenerative disorders, i.e., Parkinson's and Alzheimer's diseases. A possible option to reduce the risk of COVID-19 is vitamin D supplementation, due to its anti-inflammatory and immune-system-modulating effects. It has also been suggested that vitamin D supplementation plays a role in slowing progression of Parkinson and Alzheimer. The present study is a literature review of articles published on the theme COVID-19, Parkinson and Alzheimer's diseases, and the role played by vitamin D. PUBMED, MEDLINE, and EMBASE databases were consulted. Results confirm neurodegenerative and neuroinflammatory effects of COVID-19, aggravated in Parkinson's and Alzheimer's patients, and the important role of vitamin D as a possible therapeutic strategy. Nevertheless, randomized controlled trials and large population studies are still warranted.