The Lab4 and Memory Improvement Study

Long-term multi-species Lactobacillus and Bifidobacterium dietary supplement enhances memory and changes regional brain metabolites in middle-aged rats

SUMMARY

The main aim of the memory improvement study was to examine the impact of long-term dietary supplementation with a multi-species live Lactobacillus and Bifidobacteria mixture (Lab4) on tests of memory and behavioural flexibility in male rats.
Lab4 probiotics showed a significant improvement in long-term recognition memory in an in vivo model.
An improvement in short-term memory was observed in relation to object location.
The beneficial effects on memory were further confirmed with changes in brain metabolite profiles with Lab4 probiotic supplementation.

Aim

To examine the impact of a long-term Lab4 probiotics supplementation on memory and learning in aged rats.

Method

• The female mothers received their standard food top-dressed with Lab4 probiotics daily at dose of 100 million cfu/rat during both the gestation and postnatal period to weaning.
• 16 male pups received the same dose of Lab4 probiotics in their food from weaning until the end of the experiments.
• 16 male pups in the control group received their standard food.
• The testing commenced when the rats were 15-17 months old (equivalent to human age of 38-43 years)
• All tests were performed in accordance with the UK Animals Act and associated guidelines and EU directive 2010/63/EU. The ethical review committee at Cardiff University approved the work.

Results

Novel Object Recognition Memory

• Two identical objects were placed at equal distances from surrounding walls of the arena
• Rats were left to familiarise themselves with the objects for 4 minutes (Sample Phase)
• Rats were removed from the arena for 5 minutes (Test A)
• One object was replaced with a novel object and rats were placed back in to the arena for 4 minutes (Test Phase).
• Time spent ‘showing interest’ in the objects (familiar vs. novel) was measured
• Rats were removed from the arena for 1 hour (Test B) and then placed back in to the arena to record the contact time with the objects

The Lab4 probiotic group showed a significant improvement in long-term object novelty detection (greater preference for exploring the novel versus familiar objects, *P<0.05).

Object-in-place Memory

• Four different objects were placed at equal distances from surrounding walls of the arena
• Rats were left to familiarise themselves with the objects for 4 minutes (Sample Phase)
• Rats were removed from the arena for 5 minutes
• Two of the objects that were diagonally opposite each other were switched and rats were placed back in to the arena for 4 minutes (Test Phase).
• Time spent ‘showing interest’ in the objects (same vs. different location) was measured

The Lab4 probiotic group showed a significant improvement in short term memory for object-in-place associations (greater preference for the objects in the different spatial locations, *P<0.05).

Brain metabolites

(analysed by 1H-NMR spectroscopy at Imperial College London)
Metabolite profiles of Lab4 probiotic group and controls are clearly different in both brain regions.
The analysis showed brain region specific changes in metabolites with Lab4 probiotic supplementation suggesting changes in pathways modulating neuronal signalling.

Conclusion

Long-term supplementation with Lab4 probiotics appears to have beneficial effects on memory.

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