1 / 19

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.

nardo
Download Presentation

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

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  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

More Related