Transforming a neural circuit to function without oxygen or glucose delivery : balancing energy supply and demand in the brain
- UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
- Nikolaus Bueschke (Creator)
- Institution
- The University of North Carolina at Greensboro (UNCG )
- Web Site: http://library.uncg.edu/
- Advisor
- Santin Joseph
Abstract: Inadequate delivery of oxygen and glucose to the brain leads to disruption in circuit function and behavior that ultimately results in irreversible excitotoxicity and neuronal death. Due to the prominence of these energetic insults in ischemic strokes, drug overdoses, cardiac arrest, and other medical cases, there is an increasing interest in how to overcome these significant energetic stressors on the brain. One such method of insight has been to observe adaptations in vertebrate species that have evolved to survive low-oxygen environments. Although many hypoxia tolerant species have been identified and thoroughly studied, hypoxia tolerance is largely “hard-wired” in these species. Here, we demonstrate an animal, the American bullfrog (Lithobates catesbeianus), that is capable of massively improving its ability to survive during hypoxia and ischemia upon emergence from aquatic overwintering. Cold-acclimation induces prolonged fictive respiratory motor output in hypoxia and ischemia, where function until energetic failure shows a >20-fold improvement from warm-acclimated controls. Because network activity continues despite the apparent loss of energy delivery, we have sought to determine the different types of plasticity that occur during aquatic overwintering from both energetic and physiological standpoints to improve tolerance to energetic stress. Through a series of pharmacological experiments, we determined that energy was primarily supplied by anaerobic glycolysis, fueled in tandem by localized brain glycogen stores. In addition, the main Ca2+ permeable glutamate receptor involved in synaptic transmission, NMDA receptors, decreased Ca2+ permeability and increased desensitization in neurons following aquatic overwintering. These results suggest that energetic demands are being decreased for costly neuronal processes to compensate for reduced ATP yield. In sum, the metabolic plasticity we observe may serve as a roadmap to improve tolerance of the brain to energetic stress in other species thought to be intolerant of hypoxia. [This abstract may have been edited to remove characters that will not display in this system. Please see the PDF for the full abstract.]
Transforming a neural circuit to function without oxygen or glucose delivery : balancing energy supply and demand in the brain
PDF (Portable Document Format)
4553 KB
Created on 8/1/2022
Views: 115
Additional Information
- Publication
- Thesis
- Language: English
- Date: 2022
- Keywords
- Amphibian, Hypoxia Tolerance, Metabolism, NMDA Receptor
- Subjects
- Cerebral anoxia $x Animal models
- Cerebral ischemia $x Animal models
- Bullfrog