Supplementation with N-Acetyl Cysteine Affects Motor and Cognitive Function in Young but Not Old Mice

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ABSTRACT

Background

N-acetyl cysteine (NAC) is a thiolic antioxidant that is thought to increase cellular glutathione (GSH) by augmenting the concentration of available cysteine, an essential precursor to GSH production. Manipulating redox status can affect brain function, and NAC intake has been associated with improving brain function in models of neurodegenerative diseases.

Objectives

The objective of the study was to determine if short-term dietary supplementation with NAC could ameliorate functional impairment associated with aging.

Methods

C57BL/6J male mice aged 6, 12, or 24 mo were fed a control diet or the control diet supplemented with 0.3% NAC for a total of 12 wk. After 4 wk of dietary supplementation, mice began a series of behavioral tests to measure spontaneous activity (locomotor activity test), psychomotor performance (bridge-walking and coordinated running), and cognitive capacity (Morris water maze and discriminated active avoidance). The performance of the mice on these tests was analyzed through the use of analyses of variance with Age and Diet as factors.

Results

Supplementation of NAC improved peak motor performance in a coordinated running task by 14% (P < 0.05), and increased the time spent around the platform by 24% in a Morris water maze at age 6 mo. However, the supplementation had no to minimal effect on the motor and cognitive functions of 12- and 24-mo-old mice.

Conclusions

The findings of this preclinical study support the claim that NAC has nootropic properties in 6-mo-old mice, but suggest that it may not be useful for improving motor and cognitive impairments in older mice.

Keywords

NAC
N-acetyl cysteine
aging
motor
cognitive

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Supported by the following grants: Training in the Neurobiology of Aging (T32 AG020494) and National Institute of Health/National Institute on Aging (P01 AG022550 and R01 AG027353).