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Front. Aging Neurosci. | doi: 10.3389/fnagi.2018.00416

Probiotics and prebiotics as a therapeutic strategy to improve memory in a model of middle-aged rats

 Alejandra Romo-Araiza1, Gabriela Gutiérrez-Salmeán1, Emilio J. Galván2, Melissa Hernández-Frausto2, Gabriel Herrera-López2,  Hector Romo-Parra3,  Valentina García-Contreras1,  Ana M. Fernández-Presas4, Ricardo Jasso-Chávez5,  Cesar V. Borlongan6 and  Antonio Ibarra1*
  • 1Centro de Investigación en Ciencias de la Salud, FCS, Universidad Anáhuac México Campus Norte, Mexico
  • 2Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados (CINVESTAV), Mexico
  • 3Facultad de Psicología, Universidad Anáhuac México Campus Norte, Mexico
  • 4Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico
  • 5Departamento de Bioquímica, Instituto Nacional de Cardiología, Mexico
  • 6Center of Excellence for Aging and Brain Repair, Morsani College of Medicine, University of South Florida, United States

Aging is associated with morphological, physiological and metabolic changes, leading to multiorgan degenerative pathologies, such as cognitive function decline. It has been suggested that memory loss also involves a decrease in neurotrophic factors, including brain-derived neurotrophic factor (BDNF). In recent years, microbiota has been proposed as an essential player in brain development, as it is believed to activate BDNF secretion through butyrate production. Thus, microbiota modulation by supplementation with probiotics and prebiotics may impact cognitive decline. This study aimed to evaluate the effects of probiotics and prebiotics supplementation on the memory of middle-aged rats. Sprague-Dawley male rats were randomized in 4 groups (n=13 per group): control (water), probiotic (E. faecium), prebiotic (agave inulin), symbiotic (E. faecium + inulin), which were administered for 5 weeks by oral gavage. Spatial and associative memory were analyzed using the Morris Water Maze (MWM) and Pavlovian autoshaping tests, respectively. Hippocampus was obtained to analyze cytokines (IL-1β and TNF-α), BDNF and GABA by ELISA. Butyrate concentrations were also evaluated in feces. The symbiotic group showed a significantly better performance in MWM (p<0.01), but not in Pavlovian autoshaping test. It also showed significantly lower concentrations of pro-inflammatory cytokines (p<0.01) and the reduction in IL-1β correlated with a better performance of the symbiotic group in MWM (p<0.05). Symbiotic group also showed the highest BDNF and butyrate levels (p<0.0001). Finally, we compared the electrophysiological responses of control (n=8) and symbiotic (n=8) groups. Passive properties of CA1 pyramidal cells exhibited changes in response to the symbiotic treatment. Likewise, this group showed an increase in the N-methyl-D-aspartate receptor (NMDA)/AMPA ratio and exhibited robust long-term potentiation (LTP) (p<0.01). Integrated results suggest that symbiotics could improve age-related impaired memory.

Keywords: Associative Memory, BDNF (brain derived neurotrophic factor), butirate, Spacial memory, Symbiotic

Received: 10 Sep 2018; Accepted: 03 Dec 2018.

Edited by:

Ashok Kumar, University of Florida, United States

Reviewed by:

Tom V. Smulders, Newcastle University, United Kingdom
Brittney Yegla, University of Florida, United States  

Copyright: © 2018 Romo-Araiza, Gutiérrez-Salmeán, Galván, Hernández-Frausto, Herrera-López, Romo-Parra, García-Contreras, Fernández-Presas, Jasso-Chávez, Borlongan and Ibarra. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Antonio Ibarra, Centro de Investigación en Ciencias de la Salud, FCS, Universidad Anáhuac México Campus Norte, Huixquilucan,, 52786, Estado de Mexico, Mexico,