Neonatal brain injuries may be prevented or treated by using a gene-targeted strategy
Neonatal brain damage can now be better understood, prevented, and treated thanks to the findings of fresh preclinical study, which were published on June 15 in The Journal of Neuroscience. Throughout pregnancy, the baby typically grows with little oxygen. Prematurely born babies are forced into a high-oxygen environment that may be too much for the infant to bear. These preterm neonates frequently require aid breathing due to their undeveloped lungs. Oxygen-free radicals might form and kill cells if they receive an excessive amount of oxygen.
Premature infants often have weak antioxidant defenses that stop or delay a variety of kinds of cell damage. In the absence of appropriate therapies or preventative measures, these immature defenses cannot adequately protect against oxidative stress in a high oxygen environment, leading to damage to multiple brain regions.
According to the preclinical study, researchers from Children's National Hospital discovered that oxidative stress excessively stimulates the glucose metabolism enzyme GSK3β, changing hippocampus interneuron growth and decreasing learning and memory. These cellular and cognitive abnormalities were reversed by the researchers by inhibiting GSK3β in hippocampal interneurons.
“I am thrilled that we identified a defect in a specific cell population in the hippocampus for memory development,” stated Vittorio Gallo, Ph.D., the Children's National Research Institute's temporary chief academic officer, interim director, and the center's primary investigator for research on intellectual and developmental disabilities in the District of Columbia. “I did not think we would be able to do it at a refined level, identifying cell populations sensitive to oxidative stress and its underlying signaling pathway and molecular mechanism.”
It has not yet been determined how oxidative stress affects the developing hippocampus or how GSK3β is related to the cognitive deficiencies and neurodevelopmental abnormalities that are brought on by oxidative stress. According to Goldstein et al., the study opens up the area as a practical strategy to enhance functional recovery following newborn brain damage.
The researchers recreated prenatal brain damage by briefly raising oxygen levels in a pre-clinical animal in order to comprehend the processes underlying it better. Through this investigation, the pathophysiology and molecular processes of oxidative damage in the developing hippocampus were revealed, illuminating the causes of the cognitive abnormalities.
The researchers utilized a gene-targeted strategy to lower GSK3β levels in POMC-expressing cells or Gad2-expressing interneurons after determining what caused cellular harm. Inhibitory neurotransmission was markedly enhanced and memory problems brought on by high oxygen levels were restored by controlling the levels of GSK3β in interneurons but not in POMC-expressing cells.
Reference: “Oxidative Stress-Induced Damage to the Developing Hippocampus Is Mediated by GSK3β” by Joseph Abbah, Claire-Marie Vacher, Evan Z. Goldstein, Zhen Li, Srikanya Kundu, Brooke Talbot, Surajit Bhattacharya, Kazue Hashimoto-Torii, Li Wang, Payal Banerjee, Joseph Scafidi, Nathan A. Smith, Li-Jin Chew and Vittorio Gallo, 15 June 2022, The Journal of Neuroscience.
