Nitric Oxide Synthase in Mouse Brain Tissue that Exhibits Alzheimers Disease - PowerPoint PPT Presentation

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Nitric Oxide Synthase in Mouse Brain Tissue that Exhibits Alzheimers Disease

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Beta-amyloid plaque. http://www.ahaf.org/alzdis/about/AmyloidPlaques.htm. Introduction. Transgenic mouse model of Alzheimer's disease using species, Mus musculus ... – PowerPoint PPT presentation

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Title: Nitric Oxide Synthase in Mouse Brain Tissue that Exhibits Alzheimers Disease


1
Nitric Oxide Synthasein Mouse Brain Tissue that
Exhibits Alzheimers Disease
Patrick McCarthy 2003-04
http//www.nsrl.ttu.edu/tmot1/mus_musc.htm
2
Introduction
  • Alzheimers disease (AD)
  • Future impact
  • Characteristics

Beta-amyloid plaque
http//www.ahaf.org/alzdis/about/AmyloidPlaques.ht
m
3
Introduction
  • Transgenic mouse model of Alzheimers 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
  • Tissue preparation
  • 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 Alzheimers
Disease
  • Patrick McCarthy 2003-04
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