Newswise — Tohoku University scientists have made a groundbreaking discovery concerning the essential role of lactate in the development of neural stem cells into specialized neurons, a process known as neuronal differentiation. Through their research, they have also identified the mechanism by which lactate communicates with cells, contributing to the modification and strengthening of neuronal functions.
The study's findings were published in the Journal of Biological Chemistry on June 10, 2023.
Lactate, a byproduct of exercise and metabolism, plays a crucial role in the brain's energy supply when oxygen to cells is limited, as glucose is converted into lactate. Interestingly, during fetal brain development, lactate levels increase from the middle stages of gestation, underscoring its significant role in brain maturation and the process of neuronal differentiation.
Recent studies and reports have highlighted the vital importance of lactate in our nervous system. Lactate has been found to function as a crucial signaling molecule within the nervous system, and its metabolism is closely linked to various neuronal functions, such as neuroplasticity and memory consolidation. Nonetheless, until this recent discovery, the specific role of lactate signaling in neuronal cells had remained a mystery.
"We postulated that given the mounting evidence demonstrating lactate's role in signal-regulatory functions across various cell types under both physiological and pathological conditions, lactate may influence neuronal function by altering comprehensive gene expression," explains Professor Ryoichi Nagatomi, head of the research team and affiliated with Tohoku University's Graduate School of Biomedical Engineering. The team also includes PhD student Yidan Xu and Associate Professor Joji Kusuyama from Tokyo Medical and Dental University.
To test their hypothesis, the researchers conducted experiments focusing on gene regulation in cells treated with lactate. They specifically examined neuroblastoma cell line SH-SY5Y, where the NDRG3 protein, known to mediate gene regulation in the presence of lactate, was removed. Surprisingly, they discovered that lactate facilitates neural differentiation through pathways that rely on NDRG3 as well as independent pathways. Furthermore, the study identified two specific transcription factors, TEAD1 and ELF4, that are jointly regulated by lactate and NDRG3 during neuronal differentiation.
The research team believes that their findings not only enhance our fundamental understanding of lactate but also have the potential to be utilized as a foundation for leveraging lactate signaling to promote exercise or design drugs for preventing or managing cognitive diseases. Professor Nagatomi says, "Our discoveries offer a fresh perspective on the mechanisms by which elevated serum lactate levels induced by exercise can positively influence the nervous system. Moreover, as changes in lactate levels resulting from human exercise can be measured, considering such changes may provide better insights into adaptational alterations in brain functions, including cognition and memory function."
Looking ahead, the team plans to delve deeper into exploring the regulatory functions of lactate in neuron and brain development, aiming to uncover further valuable insights in this exciting field.
Looking ahead, the team plans to further investigate the regulatory function of lactate in neuron and brain development.
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