The broad, long-term objectives of this proposal are to understand factors involved in the regulation of brain growth and development. This research will use transgenic mice that overexpress somatostatin to study the neurobiologic consequences of increased endogenous somatostatin on brain growth and function.
The specific aims are 1) to assess the pattern of somatostatin overexpression in newborn and adult tissue 2) to study the consequences of regional overexpression on brain growth and development 3) to study the functional effects of somatostatin overexpression on receptor autoregulation, motor and avoidance behaviors, and neurotransmitter balance. The health-relatedness of the project is in the use of state-of-the-art techniques to test the hypothesis that overexpression of somatostatin during development results in disordered brain growth and/or function. The experimental design is to breed three unique lines of somatostatin transgenic mice to a homozygous state and then to study brain growth and function in transgenic and control mice. Expression analysis will be done at the message and peptide levels on dissected tissue from newborn and adult mice. The methods to be used are Southern blotting for DNA analysis, Northern blotting for RNA analysis, and radioimmunoassay, gel filtration and reverse phase high pressure liquid chromatography for peptide analysis. Tissue distribution of the peptide will be analyzed with immunocytochemistry. Brain growth will be examined by morphologic study of fetal and newborn brain. Motor activity and avoidance behavior will be assessed with standardized tests. Various pre- and post synaptic markers for cholinergic, catecholaminergic, serotonergic, and GABAergic transmitter systems will be measured.
| Wilson, M A; Kinsman, S L; Johnston, M V (1998) Expression of NMDA receptor subunit mRNA after MK-801 treatment in neonatal rats. Brain Res Dev Brain Res 109:211-20 |
| Chen, C K; Kinsman, S L; Holtzman, D M et al. (1994) A reverse transcription-polymerase chain reaction study of p75 nerve growth factor receptor gene expression in developing rat cerebellum. Int J Dev Neurosci 12:255-62 |
| Cha, J H; Kinsman, S L; Johnston, M V (1994) RNA editing of a human glutamate receptor subunit. Brain Res Mol Brain Res 22:323-8 |
