The aggression and behavioral abnormalities associated with monoamine oxidase A deficiency are rescued by acute inhibition of serotonin reuptake.
The aggression and behavioral abnormalities associated with monoamine oxidase A deficiency are rescued by acute inhibition of serotonin reuptake.
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DOI：
10.1016/j.jpsychires.2014.04.014
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发表时间：
2014-09
影响因子：
4.8
通讯作者：
Shih, Jean C.
中科院分区：
文献类型：
--
作者：
Godar, Sean C.;Bortolato, Marco;Castelli, M. Paola;Casti, Alberto;Casu, Angelo;Chen, Kevin;Ennas, M. Grazia;Tambaro, Simone;Shih, Jean C.
5-羟色胺（5-hydroxytryptamine，5-HT）神经传递的终止受5-HT转运蛋白（5-HTT）的摄取以及单胺氧化酶（monoamine oxidase，MAO）-A的降解调节。MAO-A缺乏导致广泛的行为改变，包括持续行为和社交缺陷。这些异常可能与5-HTT能稳态失衡有关;然而，5-HTT在这些异常中的作用尚不清楚。为了确定5-HTT在与MAO-A缺乏相关的行为异常中的作用，我们测试了其阻断剂氟西汀对具有亚纯型或空等位基因MAO-A突变的转基因动物的持续性、社会性和攻击性行为的行为影响。用5-HTT阻断剂氟西汀（10 mg/kg，i. p.）MAO-A敲除（KO）小鼠中的攻击行为减少，以及低形态MAO-ANeo小鼠中的社交缺陷减少。此外，这种治疗也减少了持续反应（包括大理石掩埋和水雾诱导理毛）在两个MAO-A突变基因型。两种MAO-A突变株在前额叶皮层、杏仁核和纹状体的5-HTT表达均显著降低，通过免疫组织化学检测进行定量;然而，MAO-ANeo小鼠中5-HTT的下调比KO小鼠中更普遍和广泛，可能表明低形态株在5-HT稳态方面制定代偿机制的能力更强。总之，这些发现表明，与低MAO-A活性相关的行为缺陷可能反映了5-HTT能神经元内5-HTT的发育改变。此外，翻译的影响，我们的研究结果强调5-HT再摄取抑制作为一个有趣的方法，用于控制MAO-A缺乏个体的侵略性爆发。
The termination of serotonin (5-hydroxytryptamine, 5-HT) neurotransmission is regulated by its uptake by the 5-HT transporter (5-HTT), as well as its degradation by monoamine oxidase (MAO)-A. MAO-A deficiency results in a wide set of behavioral alterations, including perseverative behaviors and social deficits. These anomalies are likely related to 5-HTergic homeostatic imbalances; however, the role of 5-HTT in these abnormalities remains unclear. To ascertain the role of 5-HTT in the behavioral anomalies associated to MAO-A deficiency, we tested the behavioral effects of its blocker fluoxetine on perseverative, social and aggressive behaviors in transgenic animals with hypomorphic or null-allele MAO-A mutations. Acute treatment with 5-HTT blocker fluoxetine (10 mg/kg, i.p.) reduced aggressive behavior in MAO-A knockout (KO) mice and social deficits in hypomorphic MAO-ANeo mice. Furthermore, this treatment also reduced perseverative responses (including marble burying and water mist-induced grooming) in both MAO-A mutant genotypes. Both MAO-A mutant lines displayed significant reductions in 5-HTT expression across the prefrontal cortex, amygdala and striatum, as quantified by immunohistochemical detection; however, the down-regulation of 5-HTT in MAO-ANeo mice was more pervasive and widespread than in their KO counterparts, possibly indicating a greater ability of the hypomorphic line to enact compensatory mechanisms with respect to 5-HT homeostasis. Collectively, these findings suggest that the behavioral deficits associated with low MAO-A activity may reflect developmental alterations of 5-HTT within 5-HTergic neurons. Furthermore, the translational implications of our results highlight 5-HT reuptake inhibition as an interesting approach for the control of aggressive outbursts in MAO-A deficient individuals.
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影响因子：
5.3
作者：
Coccaro, Emil F.;Lee, Royce J.;Kavoussi, Richard J.
通讯作者：
Kavoussi, Richard J.
影响因子：
--
作者：
Bortolato, Marco;Shih, Jean C.
通讯作者：
Shih, Jean C.
影响因子：
4.8
作者：
Coccaro, Emil F.;Noblett, Kurtis L.;McCloskey, Michael S.
通讯作者：
McCloskey, Michael S.
影响因子：
56.9
作者：
Caspi, A;McClay, J;Poulton, R
通讯作者：
Poulton, R
影响因子：
10.6
作者：
Coccaro, Emil F.;Sripada, Chandra Sekhar;Phan, K. Luan
通讯作者：
Phan, K. Luan