The major goal of this program project to develop drugs that may prove beneficial to Alzheimer's disease (AD) patients. However, paramount to the establishment of a drug or class of drugs that may have therapeutic applications in AD is the establishment of alterations (improvements or possibly further deterioration)in the neurochemical profile while undergoing drug therapy. It is therefore, the primary focus of this Neurochemical Core to establish a central laboratory facility which will support the various projects outlined in the program by providing assay service for a number of monoaminergic, amino acid and peptidergic neurochemical markers. The services provided will be as follows: To provide radioimmunoassay (RIA) and enzyme-linked immunoabsorbant assay (ELISA) service for various neuroactive peptides (corticotropin releasing hormone [CRH], neuropeptide Y [NPY], and somatostatin) and neuroactive peptides (mouse/rat beta-nerve growth factor [beta-NGF]) as well as anterior pituitary hormones (thyroid stimulating hormone [TSH]). To provide high performance liquid chromatography (HPLC) analysis of various monoaminergic neurotransmitters (norepinephrine, dopamine, epinephrine, serotonin) and their respective metabolites (homovanillic acid [HVA], 3,4-dihydroxyphenylacetic acid [DOPAC], 5-hydroxyindoleacetic acid [5- HIAA] or precursors (tryptophan [TRP]) and amino acid neurotransmitters (e.g. glutamate, glutamine, aspartate, glycine, gamma aminobutyric acid [GABA] and taurine). To provide radiometric analysis of various markers of cholinergic function (high affinity choline uptake, acetylcholine release and choline acetyltransferase [CAT] activity) in both synaptosomal preparations and cells from neuron-enriched cell cultures. To provide radioenzymatic analysis of glutamic acid decarboxylase (GAD) activity by monitoring the release of 14CO2 in both fresh and frozen brain tissue. To provide analysis of beta-adrenergic function following prolonged brain exposure to chemical delivery systems for analogues of catecholamines and beta-adrenergic agonists. Thus, the Neurochemistry Core will be integral to this program project by providing analytical service for the monitoring of the status of neurotransmitter systems while selected drugs undergo both preliminary and, perhaps, more detailed screening for potential therapeutic uses in the treatment of AD and related disorders.
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