When we learn new things, our brain cells communicate with each other through electrical and chemical signals, strengthening connections between neurons known as long-term potentiation (LTP). However, when the brain is deprived of oxygen, anoxia-induced long-term potentiation (aLTP) can occur, impairing learning and memory. Scientists at the Okinawa Institute of Science and Technology (OIST) studied the aLTP process and found that it requires the amino acid glutamate to trigger nitric oxide (NO) production, forming a positive feedback loop. This continuous presence of aLTP could hinder the brain’s memory strengthening processes, potentially explaining memory loss in stroke patients.
During a lack of oxygen, glutamate is released from neurons, leading to the production of NO in both neurons and brain blood vessels. This amplifies glutamate release in neurons during aLTP, creating a glutamate-NO-glutamate loop that persists even after oxygen levels return to normal. Understanding how oxygen depletion affects the brain is crucial, especially in conditions like stroke where memory loss can occur as a symptom. Dr. Han-Ying Wang, lead author of the study, emphasized the importance of unraveling the mechanism behind nitric oxide’s role in releasing glutamate during oxygen deficiency.
Brain tissues from mice were used to study the effects of oxygen deprivation, with cells placed in a saline solution resembling the brain’s natural environment. By replacing oxygen with nitrogen, the researchers could precisely control the duration of oxygen deprivation. They found that aLTP requires NO production in neurons, blood vessels, and astrocytes, another type of brain cell that supports communication between neurons and blood vessels. Prof. Tomoyuki Takahashi explained that sustained NO synthesis is necessary for long-term maintenance of aLTP and blocking steps in NO production or glutamate release disrupts the loop, stopping aLTP.
The cellular processes supporting aLTP overlap with those involved in memory and learning, suggesting that aLTP may hinder memory formation by hijacking molecular activities necessary for LTP. Removing aLTP can potentially restore memory enhancement mechanisms, indicating a possible link between aLTP and memory loss in stroke patients. Prof. Takahashi highlighted the significance of the positive feedback loop formed between glutamate and NO during oxygen deprivation, offering insights into how long-lasting aLTP may contribute to memory loss and suggesting potential strategies to address memory loss caused by lack of oxygen.
The study conducted by OIST researchers sheds light on the complex mechanisms underlying aLTP and its potential impact on memory and learning processes. By uncovering the role of glutamate and NO in the formation and maintenance of aLTP, the researchers have provided valuable insights into how oxygen deprivation can disrupt normal brain function. Understanding these processes may pave the way for developing new treatments for conditions like stroke that can lead to memory loss. Further research in this area could lead to innovative approaches for addressing memory deficits associated with oxygen deficiency in the brain.
