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Nitric Oxide Synthase in Mouse Brain Tissue that Exhibits Alzheimer’s Disease

Nitric Oxide Synthase in Mouse Brain Tissue that Exhibits Alzheimer’s Disease. Patrick McCarthy 2003-04. http://www.nsrl.ttu.edu/tmot1/mus_musc.htm. Introduction. Alzheimer’s disease (AD) Future impact Characteristics:. Beta-amyloid plaque.

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Nitric Oxide Synthase in Mouse Brain Tissue that Exhibits Alzheimer’s Disease

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  1. Nitric Oxide Synthasein Mouse Brain Tissue that Exhibits Alzheimer’s Disease Patrick McCarthy 2003-04 http://www.nsrl.ttu.edu/tmot1/mus_musc.htm

  2. Introduction • Alzheimer’s disease (AD) • Future impact • Characteristics: Beta-amyloid plaque http://www.ahaf.org/alzdis/about/AmyloidPlaques.htm

  3. Introduction • Transgenic mouse model of Alzheimer’s disease using species, Mus musculus • Two genetically engineered mouse types: - Transgenic positive (Tg. +): with AD-expressing gene - Transgenic negative (Tg. -): without AD- expressing gene

  4. Introduction • Nitric oxide synthase (NOS) - Enzyme throughout body • 1989, NOS in brains - Bredt et al. • Early 2000s, NOS and AD relation strongly showed - de La Torre et al., Law et al.

  5. NOS-catalyzed production of NO via L-arginine to L-citrulline pathway NOS L-arginine L-citrulline

  6. Introduction • Three NOS isoforms - neuronal NOS (nNOS) - endothelial NOS (eNOS) - inducible NOS (iNOS)

  7. Hypothesis (1) • Luth et al. found iNOS and eNOS activity increased in AD • Luth et. al and Quinn et. al found nNOS activity increased in AD • First hypothesis: total NOS activity increased in AD brains

  8. Hypothesis (2) • Norris et al. found number of nNOS-containing neurons decreased • Fewer neurons, less total concentration of nNOS • Second hypothesis: nNOS concentrations in AD brains were lower

  9. Procedure • Tissuepreparation • Determining activity - Spectrophotometer to assay

  10. Results • NOS activity significantly different (p = 0.014) • Tg. + NOS activity 58 % greater than Tg. -

  11. Procedure • Concentrations - Slot Blot - Western Blot

  12. Results Tg. + Tg. - • Intensity of band corresponds to concentrations • Darker band, higher concentration • This test inconclusive

  13. Procedure • Concentrations -ELISA assay

  14. Results • nNOS concentrations significantly different (p = 0.008) • Tg. + 36% less nNOS concentration than Tg. -

  15. Conclusion (1) Total NOS was increased in Tg. + brains (2) Concentrations of nNOS lower in Tg. + brains

  16. Conclusion • Suggest neurons initially damaged or further degenerated by the toxicity of the free radical NO • Increase in NOS activity can most likely be attributed to increase in nNOS and/or eNOS • Support the role of NOS and nNOS in AD

  17. Potential Future Studies • Find concentrations of other two isoforms of NOS, iNOS and eNOS • Use different-aged brains to study the role of NOS activity and concentration before, during, and after the onset of AD • Further test certain areas of the brain (human and mice) to investigate role in AD

  18. Acknowledgements • Dr. Ian Armitage and Dr. Bruce Martin • Abigail Tolkheim and rest of the Armitage Lab team • Ms. Lois Fruen • Team Research

  19. The Role of Nitric Oxide Synthase in Alzheimer’s Disease • Patrick McCarthy 2003-04

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