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vagoston@usuhs.mil
M.D. University Medical School Szeged, Hungary, 1976,
Ph.D. Max-Planck-Institute, Gottingen, Germany & Hungarian National Academy, Budapest, Hungary, 1992
Neurogenesis and regeneration in the developing and injured adult brain
The environment plays a critical role during both prenatal and postnatal brain development. Understanding how environmental signals alter the genetic code is critical to develop therapies to ameliorate the consequences of developmental brain disorders. Chromatin remodeling has emerged as a main molecular mechanism that can integrate environmental signals in the genetic control mechanism required for normal development. The Agoston Lab has found that there is a group of proteins that play essential role in this developmental regulation. These proteins link chromatin remodeling molecules (HDAC1, MTA2, etc.) to specific genomic sites thereby direct and localize their action only to specific genomic sites. We have identified several such "interfacing" molecules including SATB1, SATB2, AUF1, Ikaros. These proteins are specifically expressed in the developing brain and involved in regulating neurogenesis and neuronal differentiation. Deficits in these molecules result in abnormal brain development, causing seizures, mental retardation and other developmental brain disorders.
Current research focuses on the understanding of how genetic mutations can affect the functions of these molecules and how normal development can be restored in the absence of these regulator proteins.
The environment also plays an essential role in regulating neurogenesis in the adult brain. Intriguingly, environmental changes experienced by the entire organism can change the rate of stem / progenitor cell proliferation and de novo neurogenesis. In the adult hippocampus, de novo neurogenesis is increased by physical activity and by exposure to an enriched environment. Enhanced physical and social conditions provide the animals with opportunities for motor learning as they explore novel objects in their cages, for spatial learning as they acquire information on the place of water, food and other items in the cages and other kinds of learning as they interact with other animals. Studies strongly suggest that the previously observed positive "whole body experience" of enriched environment that causes increased memory performance and hippocampal neurogenesis also functional in the diseased brain. The Agoston Lab is currently working on to identify the molecular mechanism of how "enhanced environment" translates into increased adult neurogenesis and to develop a combinatorial therapy to increase neurogenesis and improve neuropsychiatric functions in various pathological conditions.
The Agoston Lab has been using a wide variety of techniques that include various protein- and nucleic acid based molecular assays, gene knock-out, histological and cell culture technologies.
Pubmed Search
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