大鼠早期蛋白质限制诱导成年后代产生失认症:BDNF-TrkB 信号在核团外壳中的关键作用。

IF 4.6 2区 医学 Q1 NEUROSCIENCES
María C. Gutiérrez , María C. Perondi , Gisella L. Tortoni , Andrea B. Cragnolini , Gabriel R. Cuadra , Analía Valdomero
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引用次数: 0

摘要

临床证据表明,早期营养不良会诱发日后与精神障碍有关的症状。然而,营养损伤诱发抑郁症的分子机制仍然未知。本研究的目的是通过关注抑郁症的核心症状--失乐症,评估围产期蛋白质限制是否会增加成年后出现抑郁样行为的脆弱性。为此,研究人员对围产期限制蛋白质摄入的雄性成年 Wistar 大鼠(PR-rats)进行了蔗糖偏好试验(SPT)、新物体识别试验(NORT)、强迫游泳试验(FST)和高架加迷宫试验(EPM),并将其与正常蛋白质饮食喂养的动物进行了比较。为了研究与早期蛋白质营养不良促进抑郁样行为相关的神经生物学底物,我们评估了脑源性神经营养因子(BDNF)及其受体TrkB在纳氏核(NAc)中的水平,并通过注入ANA-12评估了厌食样行为的逆转情况。我们发现,早期营养不良会降低蔗糖偏好,损害NORT的表现,增加FST的不动时间。此外,围产期蛋白质限制诱发的失神与 NAc 中 BDNF 和 p-TrkB 蛋白水平的升高有关,而 NAc 是奖赏回路中与失神有关的核心结构。最后,将TrkB拮抗剂ANA-12双侧注入NAc外壳可改善PR大鼠对蔗糖偏好的降低。总之,这些研究结果表明,妊娠期和哺乳期的蛋白质限制会促进日后的抑郁样行为,并可能通过改变NAc外壳中的BDNF-TrkB而增加患失张力症的风险。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Early protein restriction in rats induces anhedonia in adult offspring: A key role of BDNF-TrkB signaling in the nucleus accumbens shell

Clinical evidence suggests that early malnutrition promotes symptoms related to psychiatric disorders later in life. Nevertheless, the molecular mechanisms underpinning nutritional injury induce depression remains unknown. The purpose of the present study was to evaluate whether perinatal protein restriction increases vulnerability to developing depressive-like behavior in adulthood by focusing on anhedonia, a core symptom of depression. To this, male adult Wistar rats submitted to a protein restriction schedule at perinatal age (PR-rats), were subjected to the sucrose preference test (SPT), the novel object recognition test (NORT), the forced swim test (FST), and the elevated plus maze (EPM), and compared to animals fed with a normoprotein diet. To investigate neurobiological substrates linked to early protein undernutrition-facilitated depressive-like behavior, we assessed the levels of brain-derived neurotrophic factor (BDNF) and its receptor TrkB in the nucleus accumbens (NAc), and evaluated the reversal of anhedonic-like behavior by infusing ANA-12. We found that early malnutrition decreased sucrose preference, impaired performance in the NORT and increased immobility time in the FST. Furthermore, perinatal protein-restriction-induced anhedonia correlated with increased BDNF and p-TrkB protein levels in the NAc, a core structure in the reward circuit linked with anhedonia. Finally, bilateral infusion of the TrkB antagonist ANA-12 into the NAc shell ameliorated a reduced sucrose preference in the PR-rats.

Altogether, these findings revealed that protein restriction during pregnancy and lactation facilitates depressive-like behavior later in life and may increase the risk of developing anhedonia by altering BDNF-TrkB in the NAc shell.

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来源期刊
Neuropharmacology
Neuropharmacology 医学-神经科学
CiteScore
10.00
自引率
4.30%
发文量
288
审稿时长
45 days
期刊介绍: Neuropharmacology publishes high quality, original research and review articles within the discipline of neuroscience, especially articles with a neuropharmacological component. However, papers within any area of neuroscience will be considered. The journal does not usually accept clinical research, although preclinical neuropharmacological studies in humans may be considered. The journal only considers submissions in which the chemical structures and compositions of experimental agents are readily available in the literature or disclosed by the authors in the submitted manuscript. Only in exceptional circumstances will natural products be considered, and then only if the preparation is well defined by scientific means. Neuropharmacology publishes articles of any length (original research and reviews).
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