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产后单次静脉注射Reelin可恢复皮质酮诱导的母鼠神经化学和行为改变。

A single intravenous reelin injection restores corticosterone-induced neurochemical and behavioral alterations in dams during the post-partum period.

作者信息

Sánchez-Lafuente Carla L, Johnston Jenessa N, Reive Brady S, Scheil Kaylene K A, Halvorson Ciara S, Jimenez Mariana, Colpitts Darian, Kalynchuk Lisa E, Caruncho Hector J

机构信息

Division of Medical Sciences, University of Victoria, Victoria, BC, Canada.

出版信息

Front Mol Neurosci. 2024 Aug 20;17:1442332. doi: 10.3389/fnmol.2024.1442332. eCollection 2024.

Abstract

INTRODUCTION

Treatment with the synaptic plasticity protein reelin has rapid antidepressant-like effects in adult corticosterone (CORT)-induced depressed rats, whether administered repeatedly or acutely. However, these effects remain unexplored in the context of post-partum depression (PPD).

METHODS

This study investigated the antidepressant-like effect of a single injection of reelin in a CORT-induced model of PPD. Long-Evans female dams received either daily subcutaneous CORT (40 mg/kg) or saline injections (controls) from the post-partum day (PD) 2 to 22, and on PD22 were treated with a single intravenous reelin (3 μg) or vehicle injection.

RESULTS

Reelin treatment fully normalized to control levels the CORT-induced increase in Forced Swim Test (FST) immobility and the decrease in reelin-positive cells in the subgranular zone of the intermediate hippocampus. It also increased the number of oxytocin-positive cells in the paraventricular nucleus (PVN), the number of reelin-positive cells in the dorsal and ventral hippocampus, and the dendritic complexity of newborn neurons in the intermediate hippocampus, causing a partial recovery compared to controls. None of these changes were associated with fluctuations in estrogen levels measured peripherally.

DISCUSSION

This study brings new insights into the putative antidepressant-like effect of peripherally administered reelin in an animal model of PPD. Future studies should be conducted to investigate these effects on a dose-response paradigm and to further elucidate the mechanisms underlying the antidepressant-like effects of reelin.

摘要

引言

无论重复给药还是急性给药,用突触可塑性蛋白reelin治疗成年皮质酮(CORT)诱导的抑郁大鼠均具有快速的抗抑郁样作用。然而,在产后抑郁症(PPD)的背景下,这些作用尚未得到研究。

方法

本研究调查了单次注射reelin在CORT诱导的PPD模型中的抗抑郁样作用。Long-Evans雌性母鼠从产后第2天(PD)至第22天每天接受皮下注射CORT(40mg/kg)或生理盐水(对照组),并在PD22接受单次静脉注射reelin(3μg)或溶剂注射。

结果

reelin治疗使CORT诱导的强迫游泳试验(FST)不动时间增加以及海马中间亚颗粒区reelin阳性细胞减少完全恢复到对照水平。它还增加了室旁核(PVN)中催产素阳性细胞的数量、背侧和腹侧海马中reelin阳性细胞的数量以及海马中间新生神经元的树突复杂性,与对照组相比有部分恢复。这些变化均与外周测量的雌激素水平波动无关。

讨论

本研究为外周给予reelin在PPD动物模型中假定的抗抑郁样作用带来了新的见解。未来应进行研究以调查这些作用的剂量反应模式,并进一步阐明reelin抗抑郁样作用的潜在机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/140b/11369980/a701f595091d/fnmol-17-1442332-g001.jpg

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