Relationships of depressive behavior and sertraline treatment with walking speed and activity in older female nonhuman primates

Abstract

Depression is the most common mental health problem in aging persons and is a leading risk factor for physical disability, especially in women. Though antidepressant drugs such as serotonin reuptake inhibitors (SSRI) are commonly prescribed, epidemiological evidence reveals mixed effects of long-term antidepressant use on physical function and activity, possibly depending on depressive status. The purpose of this preclinical trial was to determine the relationships of depressive behavior and the potential for an SSRI treatment to modulate walking speed and activity patterns in older adult female cynomolgus monkeys (Macaca fascicularis). We evaluated the effects of depression and a commonly prescribed SSRI, sertraline HCl (20 mg/kg/day p.o.), on (a) walking speed, (b) accelerometry-derived activity (counts) and sedentariness (daytime 60-s sedentary epochs), and (c) observed locomotor and sedentary behaviors (% time) in adult female depressed and nondepressed monkeys (n = 42; 17.2 ± 1.8 years) during an 18 month pretreatment phase and an 18 month treatment phase using a longitudinal, stratified placebo-control study design. Monkeys that were depressed prior to treatment (19/42) subsequently had slower walking speeds (F D [1, 38] = 4.14; p ≤ 0.05) and tended to be more sedentary during the daytime (F D [1, 38] = 3.63; p ≤ 0.06). Sertraline did not affect depressive behaviors, walking speed, accelerometry-derived physical activity or sedentariness, or time observed in total locomotor or sedentary behavior (all p > 0.10). This study provides the first experimental demonstration of relationships between nonhuman primate behavioral depression and walking speed, activity, and sedentariness and provides evidence for a lack of an effect of SSRI treatment on these phenotypes.

Inflammaging phenotype in rhesus macaques is associated with a decline in epithelial barrier-protective functions and increased pro-inflammatory function in CD161-expressing cells

“…Thus, despite a pathogenic role in certain disease settings, IL17 and IL-22 have key roles in gut mucosal homeostasis, suggesting that the decreased production in older macaques could contribute to the leaky gut phenotype based on plasma biomarkers of epithelial breach and microbial translocation. Future studies to explore the relationship of leaky gut-mediated inflammation with the impaired cognitive functions in older macaques as demonstrated by previous studies (Justice et al 2017;Robinson et al 2018;Shobin et al 2017) will provide key insights into the role of imbalance in gut mucosal immunity and the gut-brain axis in morbidity of aging individuals.…”

Walking speed declines with age in male and female baboons (Papio sp.): Confirmation of findings with sex as a biological variable

“…Other papers have studied female macaques (Macaca sp. ), [5][6][7] vervets (Chlorocebus aethiops), 6,8 and baboons (Papio sp.). 3 Second, our new formula predicts age from walking speed and sex.…”

“…Third and fourth, walking speed is noninvasive, can be repeatedly tested without harm, and works in humans 1,2 and NHP. 3,[5][6][7] Future studies should address how baboon walking speed relates to morbidity and mortality, factors contributing to individual variation, and underlying mechanisms, with state-of-the-art imaging 10 and molecular 15 techniques. 14 Establishing how gait phenotypes correlate with age-related disease will enable earlier and easier identification of at-risk individuals.…”

Cerebral venous congestion promotes blood-brain barrier disruption and neuroinflammation, impairing cognitive function in mice

“…6). New investigations using transgenic animal models and rodent and primate animal models of aging (Fulop et al 2018;Reglodi et al 2018;Deepa et al 2017;Fang et al 2017;Ashpole et al 2017;Justice et al 2017;Bernier et al 2016;Mattison et al 2012;Mattison et al 2014) are needed to better understand the relationships among cerebral venous congestion, neuroinflammation and neuronal dysfunction and/or the pathogenesis of specific age-related diseases (e.g., Alzheimer's disease). Both rodent (Adamski et al 2018) and canine models of age-related heart failure could be quite relevant in that regard (Urfer et al 2017;Labinskyy et al 2007;Lei et al 2004;Lionetti et al 2005).…”