Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 108, Issue 7, Pages 3047-3052Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1010529108
Keywords
developmental programming; microbiome; basal ganglia; cognitive behavior; synapse
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Funding
- Swedish Research Council, Vinnova
- Swedish Foundation for Strategic Research
- Soderberg Foundation
- EU
- Foundation Olle Engkvist Byggmastare
- Foundation Frimurare Barnhuset
- AasterickSTAR Singapore
- AasterickSTAR
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Microbial colonization of mammals is an evolution-driven process that modulate host physiology, many of which are associated with immunity and nutrient intake. Here, we report that colonization by gut microbiota impacts mammalian brain development and subsequent adult behavior. Using measures of motor activity and anxiety-like behavior, we demonstrate that germ free (GF) mice display increased motor activity and reduced anxiety, compared with specific pathogen free (SPF) mice with a normal gut microbiota. This behavioral phenotype is associated with altered expression of genes known to be involved in second messenger pathways and synaptic long-term potentiation in brain regions implicated in motor control and anxiety-like behavior. GF mice exposed to gut microbiota early in life display similar characteristics as SPF mice, including reduced expression of PSD-95 and synaptophysin in the striatum. Hence, our results suggest that the microbial colonization process initiates signaling mechanisms that affect neuronal circuits involved in motor control and anxiety behavior.
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