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Neonatal Intermittent Hypoxia Impairs Dopamine Signaling and Executive Functioning

Abstract

Mesotelencephalic dopamine (DA) pathways are exquisitely vulnerable to ischemic-anoxic insult. These insults are known to produce long-term derangements in DA signaling and have been hypothesized to contribute, at least in part, to pathologic behaviors such as cerebral palsy, schizophrenia, and attention deficit hyperactivity disorder (ADHD). Whether modest intermittent hypoxia, such as that encountered with repetitive apneas in premature infants, contributes to clinically significant impairments in DA signaling, and how these impairments manifest at a systems level, is unknown. To address these voids there is a need to develop animal models emulating features of a common disorder of prematurity, namely, apnea with hypoxia. Behavioral traits exhibited by such models include disturbed sleep-wake architecture, excessive locomotion, and impaired working memory persisting 1 to 2 months post-insult. Western-blot analysis of expression patterns of proteins involved in DA signaling (e.g., DA and vesicular monoamine transporters, tyrosine hydroxylase, and D1 receptors) are consistent with that which might be expected from hyper- or hypodopaminergic functioning in DA-responsive prefrontal cortex and striatal circuits, respectively. These novel observations suggest that intermittent hypoxia occurring during a period of critical brain development disrupts development of those mesotelencephalic pathways modulating the expression of sleep and wakefulness, locomotion, and executive functioning.

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Correspondence to Michael J. Decker Ph.D., R.N., R.R.T..

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Decker, M.J., Rye, D.B. Neonatal Intermittent Hypoxia Impairs Dopamine Signaling and Executive Functioning. Sleep Breath 6, 205–210 (2002). https://doi.org/10.1007/s11325-002-0205-y

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Keywords

  • Dopamine
  • hypoxia
  • attention deficit disorder