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

IF 3.5 3区 医学 Q2 NEUROSCIENCES Frontiers in Molecular Neuroscience Pub Date : 2024-08-20 eCollection Date: 2024-01-01 DOI:10.3389/fnmol.2024.1442332
Carla L Sánchez-Lafuente, Jenessa N Johnston, Brady S Reive, Kaylene K A Scheil, Ciara S Halvorson, Mariana Jimenez, Darian Colpitts, Lisa E Kalynchuk, Hector J Caruncho
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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.

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单次静脉注射胰岛素可恢复产后母体由皮质酮诱导的神经化学和行为改变。
简介用突触可塑性蛋白realin治疗成年皮质酮(CORT)诱导的抑郁大鼠,无论是反复给药还是急性给药,都能迅速产生类似抗抑郁的效果。然而,这些作用在产后抑郁症(PPD)中仍未得到探讨:本研究调查了在 CORT 诱导的 PPD 模型中单次注射卷曲素的抗抑郁样作用。从产后第2天到第22天,长伊凡雌性母鼠每天皮下注射CORT(40毫克/千克)或生理盐水(对照组),并在第22天接受单次静脉注射reelin(3微克)或载体治疗:结果:胰岛素治疗可将CORT诱导的强迫游泳试验(FST)不动性增加和中间海马亚颗粒区胰岛素阳性细胞减少完全恢复到对照组水平。它还增加了室旁核(PVN)中催产素阳性细胞的数量、海马背侧和腹侧缰索素阳性细胞的数量以及中间海马新生神经元树突的复杂性,使其与对照组相比得到部分恢复。这些变化均与外周测量的雌激素水平波动无关:本研究为在PPD动物模型中外周给药Relin的抗抑郁样作用带来了新的见解。今后的研究应根据剂量-反应范式对这些效应进行调查,并进一步阐明胰岛素抗抑郁样效应的机制。
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来源期刊
CiteScore
5.70
自引率
2.10%
发文量
669
审稿时长
14 weeks
期刊介绍: Frontiers in Molecular Neuroscience is a first-tier electronic journal devoted to identifying key molecules, as well as their functions and interactions, that underlie the structure, design and function of the brain across all levels. The scope of our journal encompasses synaptic and cellular proteins, coding and non-coding RNA, and molecular mechanisms regulating cellular and dendritic RNA translation. In recent years, a plethora of new cellular and synaptic players have been identified from reduced systems, such as neuronal cultures, but the relevance of these molecules in terms of cellular and synaptic function and plasticity in the living brain and its circuits has not been validated. The effects of spine growth and density observed using gene products identified from in vitro work are frequently not reproduced in vivo. Our journal is particularly interested in studies on genetically engineered model organisms (C. elegans, Drosophila, mouse), in which alterations in key molecules underlying cellular and synaptic function and plasticity produce defined anatomical, physiological and behavioral changes. In the mouse, genetic alterations limited to particular neural circuits (olfactory bulb, motor cortex, cortical layers, hippocampal subfields, cerebellum), preferably regulated in time and on demand, are of special interest, as they sidestep potential compensatory developmental effects.
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