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. 2016 Nov 16;11(11):e0166070.
doi: 10.1371/journal.pone.0166070. eCollection 2016.

Dietary 2'-Fucosyllactose Enhances Operant Conditioning and Long-Term Potentiation via Gut-Brain Communication Through the Vagus Nerve in Rodents

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Free PMC article

Dietary 2'-Fucosyllactose Enhances Operant Conditioning and Long-Term Potentiation via Gut-Brain Communication Through the Vagus Nerve in Rodents

Enrique Vazquez et al. PLoS One. .
Free PMC article

Abstract

2´-fucosyllactose (2´-FL) is an abundant human milk oligosaccharide (HMO) in human milk with diverse biological effects. We recently reported ingested 2´-FL stimulates central nervous system (CNS) function, such as hippocampal long term potentiation (LTP) and learning and memory in rats. Conceivably the effect of 2´-FL on CNS function may be via the gut-brain axis (GBA), specifically the vagus nerve, and L-fucose (Fuc) may play a role. This study had two aims: (1) determine if the effect of ingested 2´-FL on the modulation of CNS function is dependent on the integrity of the molecule; and (2) confirm if oral 2´-FL modified hippocampal LTP and associative learning related skills in rats submitted to bilateral subdiaphragmatic vagotomy. Results showed that 2´-FL but not Fuc enhanced LTP, and vagotomy inhibited the effects of oral 2´-FL on LTP and associative learning related paradigms. Taken together, the data show that dietary 2´-FL but not its Fuc moiety affects cognitive domains and improves learning and memory in rats. This effect is dependent on vagus nerve integrity, suggesting GBA plays a role in 2´-FL-mediated cognitive benefits.

Conflict of interest statement

We have the following interests: The study has been exclusively funded by Abbott Nutrition. Abbott Nutrition manufactures infant formulas. Enrique Vazquez, Alejandro Barranco, Maria Ramirez, Maria L Jimenez, Rachael Buck and Ricardo Rueda are employed by Abbott Nutrition. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.

Figures

Fig 1
Fig 1. The chronic administration of 2’-FL potentiated LTP evoked at the hippocampal CA3-CA1 synapse in behaving rats, but this positive effect was prevented by a bilateral vagotomy.
(A) The diagram illustrated how rats were prepared for the chronic recording of fEPSPs evoked at the hippocampal CA3-CA1 synapse. Bipolar stimulation electrodes were implanted on Schaffer collaterals, while a recording tetrode was aimed at ipsilateral stratum radiatum underneath the CA1 area. (B) A LTP test was carried out in three groups of animals (Control group, black circles; Fucose group, white circles; and 2’-FL group, red circles). After 15 min of baseline records (Day 1) animals were stimulated with a HFS protocol (vertical dotted line). Recording was carried out for 30 min after the HFS protocol. Additional recordings were carried out for 15 min during two additional days (Days 2 and 3). Illustrated data were collected from n ≥ 20 electrodes/group implanted in n ≥ 5 animals/group. Note that the 2'-FL group presented significantly (*, P ≤ 0.05) larger LTP values than the other two groups. (C) An additional LTP test was carried out for four groups of animals (Control-Sham group, white circles; Control-Vagotomized group, grey circles; 2’-FL-Sham group, red circles; and, 2’-FL-Vagotomized group, black circles). Animals were stimulated for two successive days with the same HFS protocol. Recording was carried out for 30 min after the two HFS (vertical dotted lines) protocols (Days 1 and 2). Additional recordings were carried out for 15 min during three additional days (Days 3–5). Illustrated data were collected from n ≥ 20 electrodes/group implanted in n ≥ 7 animals/group. Note that the 2'-FL-Sham group presented significantly larger LTP values than the Control-Sham (▲, P ≤ 0.05), Control-VG (#, P ≤ 0.05), and 2’-FL-VG (*, P ≤ 0.05) groups at the indicated recording times. In addition, the control-Sham group presented larger LTP values than the Control-VG (●, P ≤ 0.05), and the 2’-FL-VG ($, P ≤ 0.05) groups. Finally, the 2’-FL-VG group presented larger LTP values than the Control-VG (■, P ≤ 0.05) group for the 2nd recording day, although this situation was reversed during the 4th recording day.
Fig 2
Fig 2. Chronic administration of 2’-FL potentiates the acquisition of an operant conditioning task in behaving rats, but this positive effect was prevented by a bilateral vagotomy.
(A,B) Four (Control-Sham, white bar and circles; Control-Vagotomized, grey bar and circles; 2’-FL-Sham, red bar and circles; and, 2’-FL-Vagotomized, black bar and circles) groups of rats (n = 10 per group) were trained to press a lever to obtain a food pellet using a fixed-ratio (1:1) schedule. In this situation, animals have to press the lever just one time to obtain a pellet of food. A tone provided by a loudspeaker indicated the beginning and end of the session. Each session lasted for 20 min. (C) Time to reach criterion (see Methods) for the four experimental groups in the fixed-ratio (1:1) schedule. Although no significant differences were reached between groups, the 2’-FL-Sham group presented a tendency to acquire the task faster than the 2’-FL-Vagotomized (P = 0.053) and the Control-Vagotomized (P = 0.053) groups. (D) Daily performance in the Skinner box of animals included in the four groups during the fixed-ratio (1:1) schedule. Significant differences were observed between the 2’-FL-Sham group and the 2’-FL-Vagotomized (■, P ≤ 0.05) and the Control-Vagotomized (*, P < 0.05) groups.

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Grant support

The study has been exclusively funded by Abbott Nutrition. The funder provided support in the form of salaries for authors [EV, AB, MR, MLJ, RB, RR] as well as budget for expenses associated with experimental work. The funder did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section.
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