Inhibition of progesterone receptor activity during development increases reelin-immunoreactivity in Cajal-Retzius cells, alters synaptic innervation in neonatal dentate gyrus, and impairs episodic-like memory in adulthood.
Inhibition of progesterone receptor activity during development increases reelin-immunoreactivity in Cajal-Retzius cells, alters synaptic innervation in neonatal dentate gyrus, and impairs episodic-like memory in adulthood.
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DOI：
10.1016/j.yhbeh.2020.104887
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发表时间：
2021-01
影响因子：
3.5
通讯作者：
Wagner CK
中科院分区：
文献类型：
--
作者：
Newell AJ;Chung SH;Wagner CK
孕激素受体（PR）在出生后（P1-28）在齿状回（DG）分子层的Cajal-Retzius（CR）细胞中表达，这是齿状回及其回路发育的关键阶段。CR细胞分泌糖蛋白reelin，这是DG及其连接的典型发育所必需的，特别是来自穿通通路的传入输入。该通路调节来自内嗅皮层的感觉信息的处理，并整合这些信息以形成情景记忆。为了评估PR活性对这些连接和相关行为的发展的潜在作用，从P1到7每天用PR拮抗剂RU 486处理大鼠。RU 486处理增加了reelin-ir细胞的数量，表明reelin的积累，并暗示PR调节CR细胞的主要发育功能。RU 486还改变了突触终扣标记，突触素-IR，在性别特异性的方式，这表明PR活动的分子层（MOL）的穿通通路神经支配的发展中的作用。最后，对照组和RU 486治疗组大鼠在相对近因任务中与时间上遥远的物体一起花费了显著更多的时间，这表明两组中对物体身份和时间顺序的完整联想记忆。相反，与对照组相比，相同的RU 486处理的大鼠在类似情节的记忆任务中受损，无法整合对象身份（“什么”）、时间（“何时”）和对象位置（“哪里”）。这些发现揭示了PR在调节MOL内CR细胞功能方面的新作用，从而改变DG连接和行为功能的发展。
Progesterone receptor (PR) is expressed in Cajal-Retzius (CR) cells of the dentate gyrus (DG) molecular layer during the postnatal period (P1–28), a critical stage of development for the dentate gyrus and its circuitry. CR cells secrete the glycoprotein, reelin, which is required for typical development of the DG and its connections, particularly afferent input from the perforant path. This pathway regulates the processing of sensory information arriving from entorhinal cortex and integrates this information to form episodic memories. To assess the potential role of PR activity on the development of these connections and associated behavior, rats were treated daily from P1 to 7 with the PR antagonist, RU486. RU486 treatment increased the number of reelin-ir cells, suggesting an accumulation of reelin, and implicating PR in the regulation of a principle developmental function of CR cells. RU486 also altered the synaptic bouton marker, synaptophysin-ir, in a sex-specific manner, suggesting a role for PR activity in the development of perforant path innervation of the molecular layer (MOL). Finally, both control and RU486 treated rats spent significantly more time with a temporally distant object in the Relative Recency task, suggesting an intact associative memory for object identity and temporal order in both groups. In contrast, the same RU486 treated rats were impaired in an episodic-like memory task compared to controls, failing to integrate object identity (‘what’), time (‘when’), and object position (‘where’). These findings reveal a novel role for PR in regulating CR cell function within the MOL, thereby altering development of DG connectivity and behavioral function.