Current Projects: Neurodevelopment
Our ongoing research and clinical interests focus upon how mild, perhaps even “subclinical,” events that occur during the perinatal period of critical brain development lead to disorders of minimal brain dysfunction. Our specific interests focus upon defining hypoxia-induced changes within neural pathways and processes that lead to symptoms of fatigue, hypersomnolence, executive dysfunction, and impaired response to stress.
Our ongoing lines of scientific inquiry explore the following questions:
- Which neurochemical pathways are most vulnerable to hypoxia during the perinatal period?
- At what point in life do changes in brain neurochemistry/function, induced by perinatal hypoxic insults, become apparent?
- How do we maximize remaining function within those brain circuits that are impaired?
- How do we confer neuroprotection to the fetal or newborn brain “at–risk” for adverse events?
Our program of research has identified previously unrecognized reductions in brain neurotransmitter levels within adolescent and adult (model organisms) that experienced brief, perhaps even subclinical, hypoxic insults shortly after birth. Specifically, we have observed a persistently “hypodopaminergic” state within the post-hypoxic brain that is accompanied by “symptoms” of increased sleep, impaired working memory, enhanced responsiveness to novelty and locomotor hyperactivity. These and other findings suggest that mild hypoxic events occurring the perinatal period do indeed induce neuropathology consistent with disorders of minimal brain dysfunction.
Relevant Neurodevelopment Publications
- Decker M.J., Jones K.A., Solomon I.G., Keating G.L., Rye D.B. Reduced Extracellular Dopamine and Increased Responsiveness to Novelty: Neurochemical and Behavioral Sequelae of Intermittent Hypoxia. SLEEP 2005, 28(2);169-176. Accompanying Editorial SLEEP 28;2 165-167.
- Boss V., Sola A. Wen T.C., Decker M.J. Mild Intermittent Hypoxia Does Not Induce Stress Responses in the Neonatal Rat Brain. Biol Neonate 2005;88:313-320
- Decker M.J., Hue G.E., Caudle W.M., Miller G.W., Keating G.L., Rye D.B. Episodic neonatal hypoxia evokes executive dysfunction and regionally specific alterations in markers of dopamine signaling (Neurosci, 2003 117:417-4252).
- Decker M.J., Rye D.B. Emerging Research: Neonatal intermittent hypoxia impairs dopamine signaling and executive functioning. Sleep Breath. 2002 Dec;6(4):205-10
- Berkeley JL, Decker M.J, and Levey AI. The Role of Muscarinic Acetylcholine Receptor-Mediated Activation of Extracellular Signal-Regulated Kinase 1/2 in Pilocarpine-Induced Seizures. J Neurochem, 82; 192-201, 2002.