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研究者は、無脊椎動物の主要な神経伝達物質であり、哺乳動物に少量存在するオクトパミンが、哺乳動物の脳内の細胞と相互作用して細胞死を防ぐ方法を明らかにしました。 科学者たちは、オクトパミンがマウスの大脳皮質からの星状細胞培養物に特定のレベルで導入されると、乳酸産生を引き起こし、細胞の生存を促進することを発見しました. これらの発見は、哺乳類の脳におけるオクトパミンの機能に光を当てるため、非常に重要です。これは、ATP 不足による細胞死を防ぐために星状細胞にエネルギーを生成させる SOS シグナルに例えられます。 この発見は、アルツハイマー病、パーキンソン病、双極性障害など、すべてオクトパミン レベルの不均衡に関連する症状の治療法の開発に貢献する可能性があります。 クレジット: ノースウェスタン大学
Northwestern Medicine の科学者は、哺乳類に微量に存在する神経伝達物質であるオクトパミンが脳細胞と相互作用して細胞死を防ぐことを発見しました。 この研究では、アストロサイト培養にオクトパミンを導入すると、乳酸産生が誘発され、細胞の生存が促進されることがわかりました。 オクトパミンの役割に関するこの理解は、次のような調節不全のオクトパミンレベルに関連する神経変性疾患および精神障害の将来の治療法に役立つ可能性があります。[{” attribute=””>Alzheimer’s, Parkinson’s, and bipolar disorder.
Northwestern Medicine scientists have discovered how octopamine, the major “fight-or-flight” neurotransmitter in invertebrates, communicates with other cells in mammalian brains to prevent cell death, according to a study published in the Proceedings of the National Academy of Sciences.
Although octopamine is still found in the mammalian brain in trace amounts, its function has been replaced by epinephrine. Long thought to have been an evolutionary leftover in mammals, the role of octopamine in the human brain has not previously been well understood.
In the current study, investigators first set out to understand how astrocytes, which make up the majority of cells in the human central nervous system, contribute to brain dysfunction in neurodegenerative diseases. In astrocyte cultures from the cerebral cortex of mice, scientists found that introducing octopamine at certain levels prompted the production of lactate in the astrocytes, promoting cell survival.
“Our findings are significant because we found a way in which this trace amine, octopamine, operates in the mammalian brain,” said Gabriela Caraveo Piso, PhD, assistant professor in the Ken and Ruth Davee Department of Neurology Division of Movement Disorders. “Think of it like an SOS signal; Neurons that are stressed send out this signal to astrocytes to send them energy, to send lactate. At the right level, octopamine allows astrocytes to read this distress signal and start making energy which will protect the cells from death by lack of ATP. If there’s too much octopamine, it’s sort of like smoke getting in the way of the SOS. It can’t be read by the astrocytes.”
The findings could help inform future therapies for Alzheimer’s disease, Parkinson’s, and bipolar disorder, all of which have been associated with dysregulated levels of octopamine in the brain, Caraveo Piso said.
“Lactate was thought of as a waste product for a long time. But it turns out that it is not, it is a very important fuel that the neurons need to convert to higher forms of energy,” Caraveo Piso said. “We think this is important because this can impact other diseases where octopamine levels are altered, including Alzheimer’s disease and psychiatric disorders.”
Moving forward, Piso and her collaborators hope to better understand how octopamine operates in healthy brains.
“What we want to know now is: Does this only happen under disease-like conditions? Or does octopamine play a role under physiological conditions such as learning and memory, where neurons also experience high energic demands?” Caraveo Piso said. “Given that octopamine can harness lactate metabolism in astrocytes, we are also interested in understanding the role of lactate metabolism in the brain in this context of memory and learning and aging.”
Reference: “Octopamine metabolically reprograms astrocytes to confer neuroprotection against α-synuclein” by Andrew Shum, Sofia Zaichick, Gregory S. McElroy, Karis D’Alessandro, Milad J. Alasady, Michaela Novakovic, Wesley Peng, Ekaterina A. Grebenik, Daayun Chung, Margaret E. Flanagan, Roger Smith, Alejandro Morales, Laetitia Stumpf, Kaitlyn McGrath, Dimitri Krainc, Marc L. Mendillo, Murali Prakriya, Navdeep S. Chandel and Gabriela Caraveo, 17 April 2023, Proceedings of the National Academy of Sciences.
DOI: 10.1073/pnas.2217396120
This study was supported by the Northwestern University Clinical and Translational Sciences Institute, the Parkinson’s Foundation, and the National Institute of Neurological Disorders and Stroke Grant R01 NS117750.
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