Abstract
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 four 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 was analyzed using the Morris Water Maze (MWM) and Pavlovian autoshaping tests, respectively. Hippocampus was obtained to analyze cytokines [interleukin (IL-1β) and tumor necrosis factor (TNF-α)], BDNF and γ-aminobutyric acid (GABA) by enzyme-linked immunosorbent assay (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 (PCs) 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.
Highlights
Aging is associated with multiorgan degenerative changes, including those of the central nervous system; cerebral aging leads to cognitive decline that affects explicit memory and learning, which are dependent of the hippocampus (Moreno Fernández et al, 2013).Mild cognitive impairment (MCI) is often referred as an intermediate stage between healthy aging and dementia, and it is estimated that 30%–100% of patients with MCI will evolve to the latter (Alberca Serrano and López Pousam, 2011)
Our results revealed a significant increase in the absolute concentration of butyrate after inulin and symbiotic supplementation
The present study showed that symbiotic therapy was able to diminish inflammatory markers like IL-1β and tumor necrosis factor (TNF)- α, in addition, the decrease of this cytokines significantly correlated with a better performance in memory and learning tests
Summary
Aging is associated with multiorgan degenerative changes, including those of the central nervous system; cerebral aging leads to cognitive decline that affects explicit memory and learning, which are dependent of the hippocampus (Moreno Fernández et al, 2013).Mild cognitive impairment (MCI) is often referred as an intermediate stage between healthy aging and dementia, and it is estimated that 30%–100% of patients with MCI will evolve to the latter (Alberca Serrano and López Pousam, 2011). MCI is associated with neuronal loss among the hippocampus, which, in turn, might be related with mitochondrial alterations and oxidative stress that leads to increased concentrations of pro-inflammatory cytokines such as interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α (Mufson et al, 2012; Butterfield, 2014; Baierle et al, 2015) These changes lead to neuroinflammation with an increased activity of microglia (Cevenini et al, 2013). Neuroinflammation is associated with cognitive impairment and memory decline, as the hippocampus is prone to develop alterations in synaptic transmission and plasticity during inflammation (Di Filippo et al, 2013) The latter leads to poor assembly of glutamate with N-methyl-D-aspartate receptor (NMDAR), reducing the number of such receptors within the dentate gyrus and CA1 and CA3 regions of the hippocampus (Kumar, 2011). Neuroinflammation negatively affects hippocampal gene expression of the brain-derived neurotrophic factor (BDNF), a molecule that is closely related to synaptic plasticity and, to memory consolidation (Ryan and Nolan, 2016; Mora, 2013; Moreno Fernández et al, 2013)
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