Fast-acting antidepressant-like effects of Reelin evaluated in the repeated-corticosterone chronic stress paradigm
Fast-acting antidepressant-like effects of Reelin evaluated in the repeated-corticosterone chronic stress paradigm
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DOI：
10.1038/s41386-020-0609-z
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发表时间：
2020-01-11
影响因子：
7.6
通讯作者：
Kalynchuk, Lisa E.
中科院分区：
文献类型：
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作者：
Brymer, Kyle J.;Johnston, Jenessa;Kalynchuk, Lisa E.
本报告探讨了重复或单次海马内Reelin输注对重复皮质酮（CORT）范式中抑郁样行为、认知和海马神经发生的影响。大鼠接受皮下注射CORT 3周，并在CORT注射的第7、14和21天或仅在第21天通过插入的套管在左侧海马中输注Reelin。CORT增加了强迫游泳测试中的不动性，并损害了物体位置记忆。值得注意的是，这些作用被重复和单次Reelin输注逆转。CORT降低了齿状回颗粒下区中双皮质素标记的成熟新生神经元的数量和复杂性，并且单Reelin输注增加了新生神经元的数量但不增加其复杂性，而重复的Reelin输注恢复了两者。注射AMPA拮抗剂CNQX阻断了Reelin对行为表型的拯救，但完全阻断了Reelin对海马神经发生的影响。Reelin能够挽救由CORT引起的AMPA、NMDA、GABA（A）受体、mTOR和p-mTOR的缺陷。这些新的结果表明，一个单一的海马内Reelin输注到背海马具有快速作用的抗抑郁样作用，这些影响中的一些可能是至少部分独立的Reelin行动海马神经发生。
The present report examines the effects of repeated or single intrahippocampal Reelin infusions on measures of depressive-like behavior, cognition, and hippocampal neurogenesis in the repeated-corticosterone (CORT) paradigm. Rats received subcutaneous injections of CORT for 3 weeks and Reelin was infused through an inserted canula in the left hippocampus on days 7, 14, and 21, or only on day 21 of CORT injections. CORT increased immobility in the forced-swim test and impaired object-location memory. Notably, these effects were reversed by both repeated and single-Reelin infusions. CORT decreased both the number and complexity of doublecortin-labeled maturing newborn neurons in the dentate gyrus subgranular zone, and a single-Reelin infusion increased the number but not complexity of newborn neurons, while repeated Reelin infusions restored both. Injection of the AMPA antagonist CNQX blocked the rescue of the behavioral phenotype by Reelin but did completely block the effects of Reelin on hippocampal neurogenesis. Reelin is able to rescue the deficits in AMPA, NMDA, GABA(A) receptors, mTOR and p-mTOR induced by CORT. These novel results demonstrate that a single intrahippocampal Reelin infusion into the dorsal hippocampus has fast-acting antidepressant-like effects, and that some of these effects may be at least partially independent of Reelin actions on hippocampal neurogenesis.