Early-life experiences altered the maturation of the lateral habenula in mouse models, resulting in behavioural disorders in adulthood.
Early-life experiences altered the maturation of the lateral habenula in mouse models, resulting in behavioural disorders in adulthood.
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DOI：
10.1503/jpn.200226
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发表时间：
2021-08-04
期刊：
影响因子：
--
通讯作者：
Ichijo H
中科院分区：
文献类型：
--
作者：
Nakamura T;Kurosaki K;Kanemoto M;Sasahara M;Ichijo H
在动物实验模型中，外侧缰的异常高活动会导致焦虑或抑郁样行为。在人类中也有报道称，早期生活中的过度压力与成年人精神疾病的发作有关。这些发现提出了一个问题，即外侧缰的成熟是否受到早期生活经历的影响，这可能会影响一生的行为。我们研究了成熟的外侧缰在小鼠的基础上的神经元活动标记物和塑料组件：Zif 268/Egr 1，parvalbumin和perineuronal网。我们使用反复的母亲剥夺来研究早期生活压力的影响。首先，我们发现外侧缰在应力作用下有一个短暂的高度敏感期。外侧缰的发育经历4个时期：出生后1-9天（P1-9）、P10-20、P35前后和P35后。P10-20时外侧缰核对应力高度敏感。我们还观察到外侧缰的经验依赖性成熟。只有暴露于P10-20慢性应激的小鼠在P60表现出外侧缰特异性的变化：Zif 268/Egr 1显示出异常高的应激反应性和较少的小清蛋白神经元。这些小鼠在明暗箱测试和强迫游泳测试中表现出焦虑或抑郁样行为。外侧缰核中的小清蛋白神经元对行为改变的影响尚不清楚。了解外侧缰核神经元回路的“敏感期”以及P10-20期与P9或更早、P35或更晚的神经元回路有何不同将是非常重要的。在小鼠中，P10-20期间的早期生活压力导致成年期的晚期效应：外侧缰的过度活跃和焦虑或抑郁，表明外侧缰成熟阶段之间的神经元可塑性差异。
Abnormally high activity in the lateral habenula causes anxiety- or depression-like behaviours in animal experimental models. It has also been reported in humans that excessive stress in early life is correlated with the onset of psychiatric disorders in adults. These findings raise the question of whether maturation of the lateral habenula is affected under the influence of early-life experiences, which could govern behaviours throughout life. We examined the maturation of the lateral habenula in mice based on neuronal activity markers and plastic components: Zif268/Egr1, parvalbumin and perineuronal nets. We examined the effect of early-life stress using repeated maternal deprivation. First, we found a transient highly sensitive period of the lateral habenula under stress. The lateral habenula matured through 4 stages: postnatal days 1–9 (P1–9), P10–20, around P35 and after P35. At P10–20, the lateral habenula was highly sensitive to stress. We also observed experience-dependent maturation of the lateral habenula. Only mice exposed to chronic stress from P10–20 exhibited changes specific to the lateral habenula at P60: abnormally high stress reactivity shown by Zif268/Egr1 and fewer parvalbumin neurons. These mice showed anxiety- or depression-like behaviours in the light–dark box test and forced swim test. The effect of parvalbumin neurons in the lateral habenula on behavioural alterations remains unknown. It will be important to understand the “sensitive period” of the neuronal circuits in the lateral habenula and how the period P10–20 is different from P9 or earlier, or P35 or later. In mice, early-life stress in the period P10–20 led to late effects in adulthood: hyperactivity in the lateral habenula and anxiety or depression, indicating differences in neuronal plasticity between stages of lateral habenula maturation.
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影响因子：
4.6
作者：
Laine MA;Sokolowska E;Dudek M;Callan SA;Hyytiä P;Hovatta I
通讯作者：
Hovatta I
影响因子：
3.7
作者：
Aisa, Barbara;Tordera, Rosa;Ramirez, Maria J.
通讯作者：
Ramirez, Maria J.
影响因子：
4.6
作者：
Blume, Shannon R.;Padival, Mallika;Rosenkranz, J. Amiel
通讯作者：
Rosenkranz, J. Amiel
DOI：
10.1017/s1461145703003729
发表时间：
2003-12-01
影响因子：
4.8
作者：
MacQueen, GM;Ramakrishnan, K;Young, LT
通讯作者：
Young, LT
影响因子：
3
作者：
Pena, Catherine Jensen;Nestler, Eric J.;Bagot, Rosemary C.
通讯作者：
Bagot, Rosemary C.