Japanese researchers designed a novel behavioural sequencing reverse task with a touchscreen device and pellet dispenser to assess cognitive flexibility in mice administered a Bifal and Arg mixture.
Spot sequences were displayed on screen and mice rewarded when active spots on the correct diagonal were selected, while incorrect responses went unrewarded. The same tests were repeated with active and inactive spots reversed to compare response parameters.
Mice in the test group switched to the new diagonal correct move after reversal faster than the control, which demonstrates the mixture’s ability to improve cognitive flexibility, the authors assert.
“The present results clearly demonstrate the possibility of enhanced cognitive flexibility with the administration of Bifal + Arg in mice,” they write in the report published in 'Frontiers in Nutrition'.
“We conclude that the administration of Bifal + Arg improves cognitive flexibility. This study provides the first evidence that intestinal environmental control using functional food can improve cognitive flexibility.”
Influence of gut-brain axis
Cognitive flexibility describes the ability to “organise appropriate goal-directed actions in an ever-changing environment”, the authors explain.
“Difficulties in cognitive flexibility are observed in various neuropsychiatric diseases such as autism, attention deficit hyperactivity disorder, obsessive-compulsive disorder, schizophrenia, and dementia during all life stages.
“In the case of dementia, an impairment in cognitive flexibility appears during the early stages as a delay in adaptation to a changing environment, which may be recoverable; hence, cognitive flexibility may be considered a therapeutic target for preventing the onset and/or progression of dementia.”
Intestinal microbiota dysbiosis affects bi-directional signalling to the brain via the nervous system and neurotransmitters, which impairs cognitive flexibility. Furthermore, cognitive decline is exacerbated by age-related decreased polyamine concentrations in tissues and organs (including the brain).
Earlier research found Bifal + Arg promote production of intestinal bacteria-derived polyamines and improved spatial learning memory in aged mice, but effects on cognitive flexibility have not yet been reported, they explain.
Trial mice (9-23 weeks old) were randomly assigned to the test or control group. Test mice were treated with Bifidobacterium animalis subsp. lactis LKM512 suspended in Dulbecco’s phosphate-buffered saline (D-PBS) solution containing L-Arg (0.1 mg/g body weight). Control mice were treated with D-PBS only.
Behavioural sequencing tasks was performed in 10 sessions with each comprising 150 trials of 60 minutes.
Behaviour was assessed in relation to percentage of incorrect diagonal spot choices; rate of three choosing patterns after correct spot choice in the acquisition phase, and cumulative diagonal correct or error move count.
Statistical analyses were performed using SPSS Statistics version 22 and behavioural data compared using a two-way repeated measure ANOVA (Bonferroni correction).
Based on findings, the team speculate that Bifal + Arg may influence brain function through the intestinal microbiota-gut-brain axis via polyamines. They note that antibiotic-induced dysbiosis impaired brain function, “suggesting that metabolite-derived microbiota, including polyamines, are probably involved in cognitive flexibility”.
The test group showed gradually decreasing 1st choice incorrect diagonal rate in the first sessions in each stage, which suggests Bifal + Arg promotes the formation of reversal learning-set, the team writes.
Moreover, Bifal + Arg “induced the early onset of the optimal behaviour upon a change from past experiences through repeated reversal tasks, that is, enhanced cognitive flexibility,” although the detailed underlying mechanism remains unclear, they say.
This is the first study to demonstrate the effect of intestinal microbial control on cognitive flexibility and offers compelling evidence to support therapeutic intervention with probiotics, prebiotics or synbiotics to prevent onset and/or progression of dementia, they add.
Source: Frontiers in Nutrition
Published online, June 6, 2023: http://doi/10.3389/fnut.2023.1164809
‘Bifidobacterium animalis subsp. lactis and arginine mixture intake improves cognitive flexibility in mice’
Authors: Kayo Ikuta, Daisuke Joho, Masaki Kakeyama and Mitsuharu Matsumoto
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