The title of this Program Projects Application """"""""Excitatory Transmitters, Memory, Aging and Dementia"""""""" accurately identifies the several closely related themes that the proposed research addresses. The principal excitatory neurotransmitters in the mammalian CNS are glutamate (Glu) and acetylcholine (ACh). Both of these transmitters act at multiple receptor subtypes; either hyperstimulation or blockade of either Glu or ACh receptors is associated with neuropathological changes in animal brain and/or memory/cognitive disturbances in animals and humans. Within the framework of two cores and seven separate projects, the Principal Investigator, 11 Co-investigators and 7 Consultant/Collaborators will study mechanisms by which excitatory transmitters, either in early adulthood or old age, can contribute to normal memory/cognitive functions or to memory/cognitive impairment, neuronal degeneration and cell death. A major emphasis of the research will be on identifying mechanisms of neuronal degeneration that might help explain the pathophysiology of Alzheimer's disease. One project pertains to human subjects and will involve the measurement of excitotoxic amino acids (Glu, aspartate, glycine, cysteine) in cerebrospinal fluid and blood of clinically characterized AD patients in different stages of the illness. The remainder of the proposed research comprises either in vivo or in vitro animal experiments. A wide range of neurochemical, neuropharmacological, neurophysiological, neurobehavioral, neurohistological and molecular biological or immunobiological methods will be employed, including the use of nucleotide and immunological probes for studying subtypes of excitatory amino acid and muscarinic cholinergic receptors which have recently been cloned.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZAG1-BJS-3 (01))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Washington University
Schools of Medicine
Saint Louis
United States
Zip Code
Farber, Nuri B; Creeley, Catherine E; Olney, John W (2010) Alcohol-induced neuroapoptosis in the fetal macaque brain. Neurobiol Dis 40:200-6
Creeley, Catherine E; Wozniak, David F; Nardi, Anthony et al. (2008) Donepezil markedly potentiates memantine neurotoxicity in the adult rat brain. Neurobiol Aging 29:153-67
Wozniak, David F; Xiao, Maolei; Xu, Lin et al. (2007) Impaired spatial learning and defective theta burst induced LTP in mice lacking fibroblast growth factor 14. Neurobiol Dis 26:14-26
Nikizad, H; Yon, J-H; Carter, L B et al. (2007) Early exposure to general anesthesia causes significant neuronal deletion in the developing rat brain. Ann N Y Acad Sci 1122:69-82
Xiao, Maolei; Xu, Lin; Laezza, Fernanda et al. (2007) Impaired hippocampal synaptic transmission and plasticity in mice lacking fibroblast growth factor 14. Mol Cell Neurosci 34:366-77
Todorovic, Slobodan M; Jevtovic-Todorovic, Vesna (2006) The role of T-type calcium channels in peripheral and central pain processing. CNS Neurol Disord Drug Targets 5:639-53
Lu, Lucy X; Yon, Jun-Heum; Carter, Lisa B et al. (2006) General anesthesia activates BDNF-dependent neuroapoptosis in the developing rat brain. Apoptosis 11:1603-15
Creeley, Catherine; Wozniak, David F; Labruyere, Joanne et al. (2006) Low doses of memantine disrupt memory in adult rats. J Neurosci 26:3923-32
Yon, Jun-Heum; Carter, Lisa B; Reiter, Russel J et al. (2006) Melatonin reduces the severity of anesthesia-induced apoptotic neurodegeneration in the developing rat brain. Neurobiol Dis 21:522-30
Pathirathna, Sriyani; Covey, Douglas F; Todorovic, Slobodan M et al. (2006) Differential effects of endogenous cysteine analogs on peripheral thermal nociception in intact rats. Pain 125:53-64

Showing the most recent 10 out of 130 publications