Probiotic treatment with subsp. LKM512 + arginine improves cognitive flexibility in middle-aged mice.

Cognitive flexibility, the ability of adapting to an ever-changing environment, declines with aging and impaired in early stages of dementia. Although recent studies have indicated there is a relationship between the intestinal microbiota and cognitive function, few studies have shown relationships between intestinal microbiota and cognitive flexibility because of limited behavioural tasks in mice. We recently established a novel cognitive flexibility task for mice using a touchscreen operant apparatus and found that probiotic treatment with a mixture of subsp. LKM512 and arginine improved cognitive flexibility in young adult mice. To confirm the effects of the probiotic treatment on cognitive flexibility and to determine whether it is effective even in older age, we here examined the effects of long-term treatment with subsp. LKM512 and arginine on cognitive flexibility in middle-aged mice. From 8 to 15 months of age, mice received LKM + Arg or vehicle (controls) orally three times per week and were subjected to the cognitive flexibility task at 13-15 months old. In one of indices of cognitive flexibility, both subsp. LKM512 and arginine-treated mice and vehicle-treated mice showed progressively improved performance by repeating reversal tasks, with a small trend that subsp. LKM512 and arginine-treated mice showed better learning performance through reversal phases. With respect to the other index of cognitive flexibility, subsp. LKM512 and arginine-treated mice showed significantly fewer error choices than control mice at the reversal phase, i.e. subsp. LKM512 and arginine improved the performance of behavioural sequencing acquired in the previous phase, which allowed subsp. LKM512 and arginine-treated mice to show an early onset of shift to reversal contingency. Taken together, long-term treatment with subsp. LKM512 and arginine was found to improve cognitive flexibility in middle-aged mice, indicating that probiotic treatment might contribute to prevention of age-related cognitive decline.