TANCHA: A recent study published in iScience by researchers from the Okinawa Institute of Science and Technology (OIST) and collaborators has found critical insights into how temporary oxygen deprivation impacts memory formation in the brain, shedding light on conditions like stroke.
The study focuses on anoxia-induced long-term potentiation (aLTP), a phenomenon where the brain responds to oxygen deprivation by triggering mechanisms that mimic those involved in long-term potentiation (LTP), crucial for memory strengthening and learning.
According to the findings, during episodes of oxygen deprivation, neurons release excessive amounts of the neurotransmitter glutamate. This glutamate surge leads to the production of nitric oxide (NO) in both neurons and brain blood vessels. Intriguingly, the researchers discovered that NO, in turn, amplifies the release of glutamate from neurons, creating a self-sustaining feedback loop of glutamate-NO-glutamate.
Dr. Han-Ying Wang, lead author of the study, explained, “We aimed to understand how oxygen depletion affects the brain and the underlying mechanisms. Nitric oxide’s role in glutamate release during oxygen shortage was known, but the exact mechanism remained unclear.”
Importantly, the study highlights that aLTP, sustained by this glutamate-NO feedback loop, could interfere with the brain’s normal memory consolidation processes. This hijacking of memory mechanisms potentially explains the memory loss often observed in patients following a stroke, where oxygen supply to the brain is disrupted.
Prof. Tomoyuki Takahashi, former leader of the Cellular and Molecular Synaptic Function Unit at OIST, elaborated on the implications, stating, “Continuous nitric oxide synthesis is essential for maintaining aLTP. However, disrupting steps in NO synthesis or glutamate release can halt this loop and cease aLTP.”
Stroke, a condition characterized by oxygen deprivation in the brain, frequently leads to symptoms such as amnesia, affecting recent memory recall. The researchers suggest that persistent aLTP during and after a stroke may impair the brain’s ability to strengthen memories, exacerbating memory deficits in affected individuals.
Dr. Patrick Stoney, a scientist in OIST’s Sensory and Behavioral Neuroscience Unit, underscored the potential therapeutic implications of the findings: “Understanding the malfunctioning processes in oxygen-deprived neurons could guide new strategies for treating stroke-related memory impairments.”
Prof. Takahashi emphasized the significance of establishing a positive feedback loop between glutamate and NO during oxygen deprivation. The research not only explains the prolonged effects of aLTP but also offers a pathway towards developing interventions to mitigate memory loss associated with conditions like stroke.
