Our brain cells communicate through electrical and chemical signals, strengthening their connections in long-term potentiation (LTP), which helps us learn and remember. However, another type of LTP occurs when the brain temporarily lacks oxygen, called anoxia-induced long-term potentiation (aLTP). This can impair learning and memory, possibly contributing to memory problems seen after a stroke.
Researchers at the Okinawa Institute of Science and Technology found that aLTP relies on the amino acid glutamate, which produces nitric oxide (NO), creating a feedback loop that maintains aLTP. Their study suggests that aLTP might disrupt normal memory processes, explaining memory loss in stroke patients.
When the brain lacks oxygen, neurons release large amounts of the neurotransmitter glutamate. This triggers the production of nitric oxide (NO), further increasing glutamate release and creating a glutamate-NO-glutamate loop that persists even after oxygen levels normalize.
Dr. Han-Ying Wang from the Okinawa Institute of Science and Technology (OIST) explained that while it’s known that NO helps release glutamate during oxygen shortage, the exact mechanism was unclear. During a stroke, this process can lead to memory loss or amnesia.
Brain tissues from mice were placed in a saline solution to simulate their natural environment. Usually, this solution contains oxygen, but researchers replaced it with nitrogen to deprive the cells of oxygen for specific periods.
They then examined the tissues under a microscope. They used electrodes to record the electrical activity of individual cells, stimulating them as they would be in living mice.
The scientists found that maintaining aLTP requires nitric oxide (NO) production in neurons and brain blood vessels. Researchers at OIST also discovered that astrocytes, which support neuron and blood vessel communication, are necessary for aLTP.
The continuous synthesis of NO, supported by the NO-glutamate loop, is essential for aLTP. Blocking the NO synthesis or glutamate release steps can disrupt this loop and stop aLTP.
The processes that support aLTP are similar to those involved in standard memory strengthening (LTP). When aLTP is present, it interferes with LTP, but removing aLTP can restore these memory-enhancing mechanisms. This might explain memory loss after a short stroke.
Professor Takahashi highlighted the importance of the glutamate-NO feedback loop formed during temporary oxygen deprivation. This finding explains the persistence of aLTP and may offer a solution for memory loss due to low oxygen.
Journal reference:
- Han-Ying Wang, Hiroshi Takagi, et al., Anoxia-induced hippocampal LTP is regeneratively produced by glutamate and nitric oxide from the neuro-glial-endothelial axis. iScience. DOI: 10.1016/j.isci.2024.109515.