Increased cortical neuronal responses to NMDA and improved attentional set-shifting performance in rats following prebiotic (B-GOS®) ingestion

• Published in: European neuropsychopharmacology 2018-01, Vol.28 (1), p.211-224
• Main Authors: Gronier, Benjamin, Savignac, Helene M., Di Miceli, Mathieu, Idriss, Sherif M., Tzortzis, George, Anthony, Daniel, Burnet, Philip W.J.
• Format: Article
• Language: English
• Subjects: Animals; Attention - physiology; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Cognition; Dietary Supplements; Electrophysiology; Executive Function - physiology; Glutamate; Male; Membrane Potentials - drug effects; Membrane Potentials - physiology; Microbiota; N-Methylaspartate - metabolism; Neurons - drug effects; Neurons - metabolism; Neurotransmitter Agents - pharmacology; Prebiotics - administration & dosage; Random Allocation; Rats, Sprague-Dawley; Short-chain fatty acid; Triglycerides - administration & dosage
• ISSN: 0924-977X; 1873-7862
• DOI: 10.1016/j.euroneuro.2017.11.001

We have previously shown that prebiotics (dietary fibres that augment the growth of indigenous beneficial gut bacteria) such as Bimuno™ galacto-oligosaccharides (B-GOS®), increased N-methyl-D-aspartate (NMDA) receptor levels in the rat brain. The current investigation examined the functional correlates of these changes in B-GOS®-fed rats by measuring cortical neuronal responses to NMDA using in vivo NMDA micro-iontophoresis electrophysiology, and performance in the attentional set-shifting task. Adult male rats were supplemented with B-GOS® in the drinking water 3 weeks prior to in vivo iontophoresis or behavioural testing. Cortical neuronal responses to NMDA iontophoresis, were greater (+30%) in B-GOS® administered rats compared to non-supplemented controls. The intake of B-GOS® also partially hindered the reduction of NMDA responses by the glycine site antagonist, HA-966. In the attentional set-shifting task, B-GOS® -fed rats shifted from an intra-dimensional to an extra-dimensional set in fewer trials than controls, thereby indicating greater cognitive flexibility. An initial exploration into the mechanisms revealed that rats ingesting B-GOS® had increased levels of plasma acetate, and cortical GluN2B subunits and Acetyl Co-A Carboxylase mRNA. These changes were also observed in rats fed daily for 3 weeks with glyceryl triacetate, though unlike B-GOS®, cortical histone deacetylase (HDAC1, HDAC2) mRNAs were also increased which suggested an additional epigenetic action of direct acetate supplementation. Our data demonstrate that a pro-cognitive effect of B-GOS® intake in rats is associated with an increase in cortical NMDA receptor function, but the role of circulating acetate derived from gut bacterial fermentation of this prebiotic requires further investigation.