Elsevier

Neuroscience

Volume 170, Issue 4, 10 November 2010, Pages 1179-1188
Neuroscience

Cognitive, Behavioral, and Systems Neuroscience
Research Paper
Effects of the probiotic Bifidobacterium infantis in the maternal separation model of depression

https://doi.org/10.1016/j.neuroscience.2010.08.005Get rights and content

Abstract

The concept that intestinal microbial composition not only affects the health of the gut, but also influences centrally-mediated systems involved in mood, is supported by a growing body of literature. Despite the emergent interest in brain-gut communication and its possible role in the pathogenesis of psychiatric disorders such as depression, particularly subtypes with accompanying gastrointestinal (GI) symptoms, there are few studies dedicated to the search for therapeutic solutions that address both central and peripheral facets of these illnesses. This study aims to assess the potential benefits of the probiotic Bifidobacterium infantis in the rat maternal separation (MS) model, a paradigm that has proven to be of value in the study of stress-related GI and mood disorders. MS adult rat offsprings were chronically treated with bifidobacteria or citalopram and subjected to the forced swim test (FST) to assess motivational state. Cytokine concentrations in stimulated whole blood samples, monoamine levels in the brain, and central and peripheral hypothalamic-pituitary-adrenal (HPA) axis measures were also analysed. MS reduced swim behavior and increased immobility in the FST, decreased noradrenaline (NA) content in the brain, and enhanced peripheral interleukin (IL)-6 release and amygdala corticotrophin-releasing factor mRNA levels. Probiotic treatment resulted in normalization of the immune response, reversal of behavioral deficits, and restoration of basal NA concentrations in the brainstem. These findings point to a more influential role for bifidobacteria in neural function, and suggest that probiotics may have broader therapeutic applications than previously considered.

Section snippets

Animals and housing

Pregnant Sprague–Dawley dams weighing 250–300 g were bred in the animal housing facility, University College Cork. Litters were housed in large breeding cages in a temperature- and humidity-controlled room on a 12-h light, 12-h dark cycle (lights on from 0700–1900 h). At weaning, male rats were group-housed (5–7 rats) in large cages (38×54×26 cm3). Approximately one week prior to drug treatment [postnatal day (P) 40–45], animals were singly housed in smaller polycarbonate cages (25×38×26 cm3)

Body weight

Body weights were significantly reduced in the juvenile MS rats (P35) relative to non-separated controls (effect of MS: 68.27±2.96 g vs. 83.55±3.79 g, t(31)=3.07, P<0.01; see Fig. 1). MS did not affect adult weights at P60 (159.3±12.57 g vs. 177.3±11.49 g, t(16)=0.98, P=0.34; see Fig. 1). At the end of the first week, treatment had a significant effect on body weight gain (effect of treatment: F3,32=3.59, P<0.05). Analysis showed that bifidobacteria-treated MS rats gained less weight relative

Discussion

The present data confirm, and extend, previous findings demonstrating long-term maladaptive alterations to the adult phenotype in rats exposed to repeated MS stress. The impact of MS stress was visible as early as the juvenile period (age 1 month), as evidenced by the reduced body weight in these rats relative to controls. In adulthood (2–4 months), MS induced a decrease in swim behavior and a concomitant increase in immobility in the FST, features considered to reflect a state of behavioral

Conclusion

In summary, this study provides preliminary evidence to suggest that chronic bifidobacteria treatment beneficially affects neuronal systems and behaviors relevant to depression in rats exposed to MS stress in early life, and also identifies some potential mediators of these effects. MS rats treated with the probiotic exhibit a normalization of the peripheral immune response, a reversal of behavioral deficits, and a restoration of basal NA concentrations in the pons area of the brainstem.

Acknowledgments

This study was made possible by a Centre grant (Alimentary Pharmabiotic Centre) from Science Foundation Ireland and a grant from the Higher Education Authority (PRTLI).

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