Environmental enrichment improves metabolic and behavioral health in the BTBR mouse model of autism
Environmental enrichment improves metabolic and behavioral health in the BTBR mouse model of autism
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DOI：
10.1016/j.psyneuen.2019.104476
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发表时间：
2020-01-01
影响因子：
3.7
通讯作者：
Cao, Lei
中科院分区：
文献类型：
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作者：
Queen, Nicholas J.;Boardman, Amber A.;Cao, Lei
BTBR T + Itpr 3 tf/J（BTBR）小鼠是自闭症谱系障碍（ASD）样模型，其表现出与在ASD患者中观察到的那些类似的行为和生理缺陷。虽然行为疗法是ASD患者的一线治疗，但在鼠模型中较少探索类似的非药物治疗。在这里，我们通过环境富集（EE）的方式对BTBR小鼠进行生物行为干预-一种先前显示可改善C57 BL/6小鼠全身代谢，学习/记忆，焦虑行为，神经发生，运动和免疫能力的实验性住房范例。将幼年BTBR小鼠随机分配至标准或EE圈养，并进行代谢和行为评估长达17周。EE暴露后，我们报告EE诱导的代谢和行为表型。雄性BTBR小鼠对EE有代谢反应，表现出肥胖减少、瘦体重增加、血糖控制改善和循环瘦素减少。脑源性神经营养因子（Bdnf）及其受体（Ntrk 2/TrkB）的基因表达在EE-BTBR男性的几个脑区上调。EE-BTBR雌性动物显示肥胖适度减少，血糖控制、循环瘦素或Bdnf/Ntrk 2基因表达无变化。在行为方面，EE导致焦虑减少，社会关系增加。总之，这些结果表明EE改善了BTBR小鼠的代谢和行为健康。
BTBR T + Itpr3tf/J (BTBR) mice are an Autism Spectrum Disorder (ASD)-like model that exhibit behavioral and physiological deficits similar to those observed in patients with ASD. While behavioral therapy is a first line of treatment in ASD patients, comparable non-pharmacological treatments are less explored in murine models. Here, we administer a bio-behavioral intervention for BTBR mice by way of environmental enrichment (EE) - an experimental housing paradigm previously shown to improve systemic metabolism, learning/memory, anxious behavior, neurogenesis, locomotion, and immunocompetence in C57BL/6 mice. Juvenile BTBR mice were randomized to standard or EE housing and were subjected to metabolic and behavioral assessments up to 17 weeks. Following EE exposure, we report an EE-induced metabolic and behavioral phenotype. Male BTBR mice responded metabolically to EE, displaying reduced adiposity, increased lean mass, improved glycemic control, and decreased circulating leptin. The gene expressions of brain-derived neurotrophic factor (Bdnf) and its receptor (Ntrk2/TrkB) were upregulated in several brain areas in EE-BTBR males. EE-BTBR females showed modest reduction of adiposity and no changes in glycemic control, circulating leptin, or Bdnf/Ntrk2 gene expression. With regard to behavior, EE resulted in decreased anxiety, and increased social affiliation. Together, these results suggest that EE improves metabolic and behavioral health in BTBR mice.