Adult microbiota-deficient mice have distinct dendritic morphological changes: differential effects in the amygdala and hippocampus

作者：Luczynski Pauline; Whelan Sean O; O' Sullivan Colette; Clarke Gerard; Shanahan Fergus; Dinan Timothy G; Cryan John F

来源：European Journal of Neuroscience, 2016, 44(9): 2654-2666.

DOI：10.1111/ejn.13291

<jats:title>Abstract</jats:title><jats:p>Increasing evidence implicates the microbiota in the regulation of brain and behaviour. Germ‐free mice (<jats:styled-content style="fixed-case">GF</jats:styled-content>; microbiota deficient from birth) exhibit altered stress hormone signalling and anxiety‐like behaviours as well as deficits in social cognition. Although the mechanisms underlying the ability of the gut microbiota to influence stress responsivity and behaviour remain unknown, many lines of evidence point to the amygdala and hippocampus as likely targets. Thus, the aim of this study was to determine if the volume and dendritic morphology of the amygdala and hippocampus differ in <jats:styled-content style="fixed-case">GF</jats:styled-content> versus conventionally colonized (<jats:styled-content style="fixed-case">CC</jats:styled-content>) mice. Volumetric estimates revealed significant amygdalar and hippocampal expansion in <jats:styled-content style="fixed-case">GF</jats:styled-content> compared to <jats:styled-content style="fixed-case">CC</jats:styled-content> mice. We also studied the effect of <jats:styled-content style="fixed-case">GF</jats:styled-content> status on the level of single neurons in the basolateral amygdala (<jats:styled-content style="fixed-case">BLA</jats:styled-content>) and ventral hippocampus. In the <jats:styled-content style="fixed-case">BLA</jats:styled-content>, the aspiny interneurons and pyramidal neurons of <jats:styled-content style="fixed-case">GF</jats:styled-content> mice exhibited dendritic hypertrophy. The <jats:styled-content style="fixed-case">BLA</jats:styled-content> pyramidal neurons of <jats:styled-content style="fixed-case">GF</jats:styled-content> mice had more thin, stubby and mushroom spines. In contrast, the ventral hippocampal pyramidal neurons of <jats:styled-content style="fixed-case">GF</jats:styled-content> mice were shorter, less branched and had less stubby and mushroom spines. When compared to controls, dentate granule cells of <jats:styled-content style="fixed-case">GF</jats:styled-content> mice were less branched but did not differ in spine density. These findings suggest that the microbiota is required for the normal gross morphology and ultrastructure of the amygdala and hippocampus and that this neural remodelling may contribute to the maladaptive stress responsivity and behavioural profile observed in <jats:styled-content style="fixed-case">GF</jats:styled-content> mice.</jats:p>

• 出版日期2016-11