The goal of the neuroanatomy core is to determine how the prenatal availability of choline and folate affects brain structure from development through old age. Characterization of these changes will be accomplished in collaboration with all five research projects. The core will use immunohistochemistry, in situ hybridization, and image analysis to define the organization of selected cellular classes and determine how they are affected by perinatal nutritional manipulations. Qualitative neuroanatomical analyses will include the definition of the spatial distribution, cellular morphology and the localization of relevant molecules in selected cell classes. Quantitative analyses will include measurements of cell size, volume, axonal and dendritic branching patterns and the computation of cell density and unbiased cell counts. This data will be stored in a relational database for the use of all investigators in correlational studies.
The specific aims of the neuroanatomy core are: 1) To facilitate the accomplishment of the scientific aims delineated in the individual projects of the program by providing expertise in quantitative structural techniques and other technical support as needed. Anatomical studies have been prioritized to concentrate on the most scientifically important topics in each project. These comprise the aims of the core listed below. 2) To determine the effects of prenatal choline and folate availability on the structure of the rat hippocampus, basal forebrain, and frontal cortex. The distribution and morphology of neurons containing development and aging. 3) To determine the localization of activated and non-activated mitogen activated protein kinase (MAPK) and Ca/calmodulin protein kinase II (CAMK22) in rat hippocampal slices. 4) To determine the effects of folate and choline availability on the morphology and distribution of cholinergic basal forebrain and availability on the timing and anatomical distribution of cell replication and apoptosis in fetal rat hippocampus and septum in wild type and ApoE knockout mice using BrDU and TUNEL. 6) To map the expression of brain genes that respond to the nutritional manipulations. Changes in the temporal and spatial patterns of gene expression related to changes in dietary choline and folate will be defined using DNA chip technology. Genes found to respond to dietary changes be mapped using in situ hybridization. These studies will contribute to the NIOH-supported gene expression database (GXD).
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