Drosophila mutants lacking the glial neurotransmitter-modifying enzyme Ebony exhibit low neurotransmitter levels and altered behavior.
Drosophila mutants lacking the glial neurotransmitter-modifying enzyme Ebony exhibit low neurotransmitter levels and altered behavior.
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DOI：
10.1038/s41598-023-36558-7
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发表时间：
2023-06-27
影响因子：
4.6
通讯作者：
Shirasu-Hiza, Mimi
中科院分区：
文献类型：
--
作者：
Pantalia, Meghan;Lin, Zhi;Tener, Samantha J.;Qiao, Bing;Tang, Grace;Ulgherait, Matthew;O'Connor, Reed;Delventhal, Rebecca;Volpi, Julia;Syed, Sheyum;Itzhak, Nissim;Canman, Julie C.;Fernandez, Maria de la Paz;Shirasu-Hiza, Mimi
抑制多巴胺神经递质（多巴胺，血清素）的酶，如儿茶酚-O-甲基转移酶（COMT）和单胺氧化酶（MAO），被认为可以增加神经递质水平，并被广泛用于治疗帕金森病和精神疾病，但这些酶在调节行为中的作用仍不清楚。在这里，我们调查了一个类似的酶在模式生物果蝇的遗传损失。由于酶乌木修改和失活胺神经递质，它的损失被认为是增加神经递质水平，增加行为，如侵略和求爱，减少睡眠。事实上，自1960年以来，乌木突变体被描述为“侵略性突变体”，尽管这种行为尚未被量化。使用基于自动化机器学习的分析，我们定量地证实了乌木突变体表现出增加的攻击性行为，如拳击，但也减少了求偶行为和增加了睡眠。通过组织特异性敲除，我们发现乌木在这些行为中的作用是胶质细胞特有的。出乎意料的是，对乌木大脑中胺神经递质的直接测量显示，它们的水平没有增加，而是减少了。因此，增加的攻击性是这种神经递质谱的异常行为。我们进一步发现，乌木突变体只有在相互战斗时才表现出更强的攻击性，而不是在与野生型对照组战斗时。此外，乌木突变体之间的战斗不太可能以一个明确的赢家结束，而不是控制之间的战斗或乌木突变体和控制之间的战斗。在乌木与控制的战斗中，乌木突变体更有可能获胜。总之，这些结果表明，乌木突变体只在特定的环境中表现出长期的攻击行为，与同样占主导地位的对手。
Inhibitors of enzymes that inactivate amine neurotransmitters (dopamine, serotonin), such as catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO), are thought to increase neurotransmitter levels and are widely used to treat Parkinson's disease and psychiatric disorders, yet the role of these enzymes in regulating behavior remains unclear. Here, we investigated the genetic loss of a similar enzyme in the model organism Drosophila melanogaster. Because the enzyme Ebony modifies and inactivates amine neurotransmitters, its loss is assumed to increase neurotransmitter levels, increasing behaviors such as aggression and courtship and decreasing sleep. Indeed, ebony mutants have been described since 1960 as "aggressive mutants," though this behavior has not been quantified. Using automated machine learning-based analyses, we quantitatively confirmed that ebony mutants exhibited increased aggressive behaviors such as boxing but also decreased courtship behaviors and increased sleep. Through tissue-specific knockdown, we found that ebony’s role in these behaviors was specific to glia. Unexpectedly, direct measurement of amine neurotransmitters in ebony brains revealed that their levels were not increased but reduced. Thus, increased aggression is the anomalous behavior for this neurotransmitter profile. We further found that ebony mutants exhibited increased aggression only when fighting each other, not when fighting wild-type controls. Moreover, fights between ebony mutants were less likely to end with a clear winner than fights between controls or fights between ebony mutants and controls. In ebony vs. control fights, ebony mutants were more likely to win. Together, these results suggest that ebony mutants exhibit prolonged aggressive behavior only in a specific context, with an equally dominant opponent.
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影响因子：
64.8
作者：
CROSSLEY, S;ZUILL, E
通讯作者：
ZUILL, E
影响因子：
2.8
作者：
Borycz, J.;Borycz, J. A.;Meinertzhagen, I. A.
通讯作者：
Meinertzhagen, I. A.
影响因子：
5.8
作者：
Gilestro, Giorgio F.;Cirelli, Chiara
通讯作者：
Cirelli, Chiara
DOI：
10.1073/pnas.082102599
发表时间：
2002-04-16
影响因子：
11.1
作者：
Chen, S;Lee, AY;Kravitz, EA
通讯作者：
Kravitz, EA
影响因子：
4.5
作者：
Andrews JC;Fernández MP;Yu Q;Leary GP;Leung AK;Kavanaugh MP;Kravitz EA;Certel SJ
通讯作者：
Certel SJ