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Prof. Regino Perez-Polo: Department of Biochemistry and Molecular Biology, University of Texas Medical Branch (formerly Human Biological Chemistry and Genetics)
"Primary analysis of data collected in studies partly supported by the BSF grant has shed light on several pathways that may explain the connection between pre-natal and peri-natal hypoxia and psychiatric disorders occurring later in life. We plan to continue these analyses given their clinical importance."
While an increasing number of babies from at-risk pregnancies with very low birth weight (VLBW) now survive due to modern pediatric intensive care, many of them suffer from behavioral and cognitive deficits later in life, including cerebral palsy, epilepsy, psychopathy and mental retardation. Ischemia (lack of oxygen supply) is a major cause of such brain damage, and contributes to peri-natal morbidity/mortality, affecting 0.2 to 0.4% of full-term infants and up to 40-60% of premature infants. To date, there has been little success in developing recovery mechanisms to improve outcomes in these cases.
According to Prof. Perez-Polo and Dr. Golan’s working hypothesis, oxidative stress in the nervous system triggers inflammatory responses. As a result, gene networks responsible for cell viability and function become uncoupled, leading to neural deficits during development.
Better understanding of the mechanisms underlying neuronal cell death and the deficits associated with hypoxic trauma in the CNS (Central Nervous System) are expected to lead to new approaches for reducing cognitive defects and diseases among VLBW babies.
Cooperation Prof. Perez-Polo’s team uses genomic screening and validation applied to a mouse model of hypoxia characterized by Dr. Golan to determine which brain embryonic gene groups are affected by maternal hypoxia during late pregnancy (pre-eclampsia).
Findings
Dr. Golan’s team identified gene sets undergoing major changes as a result of maternal hypoxia. She also found changes in the GABA neurotransmitter pathways in mouse fetuses subjected to hypoxia. Treating mothers with magnesium sulfate was effective to some degree in reversing these deficits in newborns.
Parvalbumin was used for analysis by the means of Affymentrix DNA arrays. An example of the DNA array raw data and gene-set expression analysis is shown (green, red and gray represent decreased, increased and no change in gene expression, respectively). Confocal image of cortical neuron, showing molecular markers for various cellular structures and functions.
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Immuno-Stained RNA Extracted from Brain Cerebellar Tissue IImmuno-stained RNA extracted from brain cerebellar tissue mmuno-stained RNA extracted from brain cerebellar tissue |
