Abstract

This grant is based on two hypotheses derived from our preliminary results: 1) that DMAB and its analog anabaseine act through one or more brain nicotinic receptor subtypes to exert behavioral, electrophysiological, cellular and biochemical actions that may have therapeutic benefits for Alzheimer's disease and related neuropathologies; and 2) that nicotinic receptors may exert a cytoprotective action in selected neurons in the neocortex or other regions by modulating intracellular calcium levels. The first hypothesis will be tested with several standard pharmacological approaches, e.g., dose response-correlations and receptor-antagonist studies involving electrophysiology, behavior, and neurochemistry, in normal and cholinergically hypofunctional animals. The second line of studies will also use a multidisciplinary approach involving electrophysiological recording of neuronal channels sensitive to intracellular calcium concentrations and primary neocortical neuronal cultures sensitive to a cytoprotective action of nicotine.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Program Projects (P01)
Project #
5P01AG010485-05
Application #
3726699
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
1995
Total Cost
Indirect Cost

  Institution

Name
University of Florida
Department
Type
DUNS #
073130411
City
Gainesville
State
FL
Country
United States
Zip Code
32611

  Publications

Richter, Frank; Koulen, Peter; Kaja, Simon (2016) N-Palmitoylethanolamine Prevents the Run-down of Amplitudes in Cortical Spreading Depression Possibly Implicating Proinflammatory Cytokine Release. Sci Rep 6:23481
Means, John C; Gerdes, Bryan C; Kaja, Simon et al. (2016) Caspase-3-Dependent Proteolytic Cleavage of Tau Causes Neurofibrillary Tangles and Results in Cognitive Impairment During Normal Aging. Neurochem Res 41:2278-88
Montgomery, Christa L; Keereetaweep, Jantana; Johnson, Heather M et al. (2016) Changes in Retinal N-Acylethanolamines and their Oxylipin Derivatives During the Development of Visual Impairment in a Mouse Model for Glaucoma. Lipids 51:857-66
Kaja, Simon; Payne, Andrew J; Singh, Tulsi et al. (2015) An optimized lactate dehydrogenase release assay for screening of drug candidates in neuroscience. J Pharmacol Toxicol Methods 73:1-6
Sarkar, Saumyendra; Jun, Sujung; Simpkins, James W (2015) Estrogen amelioration of A?-induced defects in mitochondria is mediated by mitochondrial signaling pathway involving ER?, AKAP and Drp1. Brain Res 1616:101-11
Kaja, Simon; Payne, Andrew J; Naumchuk, Yuliya et al. (2015) Plate reader-based cell viability assays for glioprotection using primary rat optic nerve head astrocytes. Exp Eye Res 138:159-66
Cheli, V T; Santiago González, D A; Spreuer, V et al. (2015) Voltage-gated Ca2+ entry promotes oligodendrocyte progenitor cell maturation and myelination in vitro. Exp Neurol 265:69-83
Kaja, Simon; Sumien, Nathalie; Shah, Vidhi V et al. (2015) Loss of Spatial Memory, Learning, and Motor Function During Normal Aging Is Accompanied by Changes in Brain Presenilin 1 and 2 Expression Levels. Mol Neurobiol 52:545-54
Kaja, S; Payne, A J; Nielsen, E Ø et al. (2015) Differential cerebellar GABAA receptor expression in mice with mutations in CaV2.1 (P/Q-type) calcium channels. Neuroscience 304:198-208
Grillo, Stephanie L; Koulen, Peter (2015) Psychophysical testing in rodent models of glaucomatous optic neuropathy. Exp Eye Res 141:154-63

Showing the most recent 10 out of 233 publications