Microtubule-Associated Protein 2 and Synaptophysin in the Preterm and Near-Term Ovine Fetal Brain and the Effect of Intermittent Umbilical Cord Occlusion

Abstract

We have determined the change in immunoreactivity (IR) for microtubule-associated protein 2 (MAP-2) and synaptophysin (SYN) as markers for dendritic and presynaptic nerve development, respectively, in the ovine fetal brain with advancing gestation and in response to intermittent umbilical cord occlusion (UCO), which might then contribute to adverse neurodevelopment. Fetal sheep (control and experimental groups preterm at 111-115 and near term at 132-138 days of gestation; term = 145 days) were studied over 4 days with UCOs performed by inflation of an occluder cuff for 90 seconds every 30 minutes for 3 to 5 hours each day. Animals were then euthanized and fetal brains assessed for IR of MAP-2 and SYN. In control animals, the IR of SYN increased in the gray matter with advancing gestation consistent with a developmental increase in presynaptic vesicles and/or nerve terminals as expected; however, the IR of MAP-2 decreased in all brain regions studied, suggesting concurrent refinement in dendritic branching and spine development. Intermittent UCO as studied with marked but limited hypoxemia resulted in a decrease in IR of SYN for the brain regions of the preterm animals when protein turnover is higher and indicates decreased presynaptic vesicle formation; whereas, MAP-2 IR was selectively increased in the hippocampus CA1 and thalamus of the near-term animals, consistent with reactive dendritic change and heightened vulnerability for neuronal injury. As such, intermittent cord compressions in the ovine fetus can impact protein markers for dendritic and presynaptic nerve development depending on their timing, which might then lead to alterations in synapse formation and neuronal circuitry.