Luczynski Pauline, Whelan Seán O, O'Sullivan Colette, Clarke Gerard, Shanahan Fergus, Dinan Timothy G, Cryan John F
APC Microbiome Institute, University College Cork, Room 3.86, Western Gateway Building, Cork, Ireland.
Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland.
Eur J Neurosci. 2016 Nov;44(9):2654-2666. doi: 10.1111/ejn.13291. Epub 2016 Jul 8.
Increasing evidence implicates the microbiota in the regulation of brain and behaviour. Germ-free mice (GF; 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 GF versus conventionally colonized (CC) mice. Volumetric estimates revealed significant amygdalar and hippocampal expansion in GF compared to CC mice. We also studied the effect of GF status on the level of single neurons in the basolateral amygdala (BLA) and ventral hippocampus. In the BLA, the aspiny interneurons and pyramidal neurons of GF mice exhibited dendritic hypertrophy. The BLA pyramidal neurons of GF mice had more thin, stubby and mushroom spines. In contrast, the ventral hippocampal pyramidal neurons of GF mice were shorter, less branched and had less stubby and mushroom spines. When compared to controls, dentate granule cells of GF 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 GF mice.
越来越多的证据表明微生物群参与大脑和行为的调节。无菌小鼠(GF;从出生起就缺乏微生物群)表现出应激激素信号改变和焦虑样行为,以及社会认知缺陷。尽管肠道微生物群影响应激反应性和行为的潜在机制尚不清楚,但许多证据表明杏仁核和海马体可能是其作用靶点。因此,本研究的目的是确定在GF小鼠与常规定殖(CC)小鼠中,杏仁核和海马体的体积和树突形态是否存在差异。体积估计显示,与CC小鼠相比,GF小鼠的杏仁核和海马体明显增大。我们还研究了GF状态对基底外侧杏仁核(BLA)和腹侧海马体单个神经元水平的影响。在BLA中,GF小鼠的无棘中间神经元和锥体神经元表现出树突肥大。GF小鼠的BLA锥体神经元有更多细的、短粗的和蘑菇状棘突。相比之下,GF小鼠的腹侧海马体锥体神经元较短,分支较少,短粗的和蘑菇状棘突也较少。与对照组相比,GF小鼠的齿状颗粒细胞分支较少,但棘突密度没有差异。这些发现表明,微生物群是杏仁核和海马体正常大体形态和超微结构所必需的,这种神经重塑可能导致在GF小鼠中观察到的适应不良的应激反应性和行为特征。
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