Abstract

Social isolation (SI) is well established as an environmental factor that negatively influences different behavioral parameters, including cognitive function, anxiety, and social interaction, depending on the age of isolation. Aging is a physiological process that is associated with changes in cognitive function, locomotor activity, anxiety and emotional responses. Few studies have investigated the effect of SI in senescence, or possible interventions. In the current study, we investigated the possible complementary effects of melatonin (MLT) and exercise (Ex) in improving SI-related behavioral changes in aged rats. Forty aged Wistar rats (24 months old) were randomly divided into five groups (n = 8 per group): Control (group housing), SI (individual housing for 7 weeks), SI + MLT (SI rats treated with 0.4 mg MLT/ml in drinking water), SI + Ex (SI rats treated with 60 min of swimming), and SI + MLT + Ex (SI rats treated with both MLT and Ex). Different behavioral tasks were conducted in the following sequence: open field test, elevated plus maze test, sucrose preference test, Y maze test, and Morris water maze test. Locomotor activities measured by total distance moved and velocity revealed that SI + Ex (P = 0.0038; P = 0.0015) and SI + MLT + Ex (P = 0.0001; P = 0.0003) significantly improved the locomotor activity compared with SI rats but SI + MLT (P = 0.0599; P = 0.0627) rats showed no significant change. Anxiety index score was significantly improved in SI + MLT + Ex (P = 0.0256) compared with SI rats while SI + MLT (P > 0.9999) and SI + Ex (P = 0.2943) rats showed no significant change. Moreover, latency to reach the platform in Morris water maze was significantly reduced at day 5 in SI + MLT + Ex (P = 0.0457) compared with SI rats but no change was detected in SI + MLT (P = 0.7314) or SI + Ex (P = 0.1676) groups. In conclusion, this study supports the possible potential of MLT in combination with Ex in improving physical activity, anxiety, and cognitive functions in aging population.

Highlights

  • Aging is a normal physiological process and a known profounding factor for several disorders

  • The effects of MLT and Ex on weight among groups were measured as the percentage of body weight change

  • A series of behavioral tests was conducted to investigate the effects of a long period of Social isolation (SI) (7 weeks) on aging and brain function in terms of locomotor function (TDM, velocity, rearing, immobility), anxiety, depression (SPT) and cognitive function [Y maze, and MWM]

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Summary

Introduction

Aging is a normal physiological process and a known profounding factor for several disorders. Expansion of aging population raised many challenges and several concerns at national and international levels Alzheimer’s disease (AD) is one of the most known age-associated disease and a leading cause of dementia (Xia et al, 2018). According to AD association (2020), 10% of the American population age 65 and older has Alzheimer’s dementia (Jayaraj et al, 2020). The risk of AD is exponentially rise with age to affect one every three people with age over 85 (Abyad, 2016; Jayaraj et al, 2020). Geriatric research is expanding to reflect the importance of understanding the aging process and investigating some possible intervention of age-linked diseases. several studies have reported age-associated learning and memory impairment in different maze tests (Rapp et al, 1987; Gallagher et al, 1993; ShukittHale et al, 2004; Robitsek et al, 2008; Mizoguchi et al, 2009) and high anxiety-related behavior in the open field and elevated plus maze (EPM) tests (File, 1990; Rowe et al, 1998; Darwish et al, 2001; Boguszewski and Zagrodzka, 2002; Bessa et al, 2005) compared with adulthood

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