20110509_ISMRM 2011_Umer

Views:
 
     
 

Presentation Description

No description available.

Comments

Presentation Transcript

Aging impacts significantly on neuronal transport in normal mice but not in an accelerated mouse model of Amyloid Beta pathology.:

Aging impacts significantly on neuronal transport in normal mice but not in an accelerated mouse model of Amyloid Beta pathology. U. A. Khan1, A. Bertrand1,2, H. M. Dung1, D. Novikov1, L. K. Hill1, B. W. Little1, H. B. Rajamohamed Sait3, M. Shamsie1, E. M. Sigurdsson3, and Y. Z. Wadghiri1 1Radiology, New York University Langone Medical Center, New York, NY, United States, 2URA CEA-CNRS 2210, Mircen , Fontenay -Aux-Roses, France, 3Physiology & Neuroscience, New York University Langone Medical Center, New York, NY, United States

Declaration of Relevant Financial Interests or Relationships:

Declaration of Relevant Financial Interests or Relationships Umer Khan I have no relevant financial interest or relationship to disclose with regard to the subject matter of this presentation .

Manganese-enhanced MRI & neuronal transport:

Manganese-enhanced MRI & neuronal transport Mn uptake Ca 2+ channels Mn transport along microtubules - Mitochondria and transport vesicles Mn synaptic transmission Synaptic vesicles MRI 24h after instillation of MnCl in the nostril Lateral olfactory tract Olfactory epithelium Olfactory bulb MRI before Mn 2 + instillation Piriform cortex Pautler et al, MRM, 1998

PowerPoint Presentation:

MEMRI, Neuronal transport & Alzheimer’s disease Bertrand et al, ISMRM 2011 Cross et al, Neuroimage ,2008 Aging effects on transport speed Amyloid b and Tau pathology effects on transport speed Smith et al, Neuroimage 2007 P301L

Accelerated amyloid b mouse model: 5xFAD: Tg6799:

Accelerated amyloid b mouse model: 5xFAD : Tg6799 Cerebral A b 42 levels Model examined Model studied in Smith et al. Oakley et al, Neurobio of A. 2006

Oflactory Bulb Histology at 6 months:

Oflactory Bulb Histology at 6 months Amyloid plaques deposition in the olfactory bulb of Tg6799 mouse model 6E10-4G8 anti- A b Staining x5 magnification x40 magnification

Track Tracing-MEMRI in a mouse model of Amyloid pathology:

Track Tracing-MEMRI in a mouse model of Amyloid pathology 3 month old : 5 xFAD (n=5) and WT (n=7) 6 month old: 5xFAD (n=8) and WT (n=8) MEMRI of the olfactory tract Mn instillation : 1.5 microL of MnCl 2.5M in one nostril 9 MRI sessions 3D SPGR T1 (15 min) Spatial resolution : (150µm) 3 TR/TE=15/4 ms 2 regions of interest Glomerular layer Mitral cell layer H0 H1 H4 H8 H12 H24 H36 D7 H48 H0 H1 H4 H8 H12 H24 H36 H48 D7

Analysis of TT-MEMRI curves:

Analysis of TT-MEMRI curves Bertrand et al, Curr I R, 2011 Maximal Signal (Smax) Time to Smax (t2Smax) Maximal S lope (Vmax) Time to Vmax (t2Vmax) Normalized signal intensity as a function of time

Amyloid b and aging effect not seen in Tg Mice:

Amyloid b and aging effect not seen in Tg Mice M3, n = 5 M6, n = 8 Day 1 Day 2 Day 3 Day 7

Plaque and aging effect not seen in Tg Mice:

Plaque and aging effect not seen in Tg Mice Maximal Signal Not Significant Time to Max Signal Not Significant Maximal S lope Not Significant Time to Max Slope Not Significant Normalized signal intensity as a function of time Glomerular L Mitral C L

Significant decrease in Mn Transport with age in WT mice :

Significant decrease in Mn Transport with age in WT mice Day 1 Day 2 Day 3 Day 7 M3, n = 7 M6, n = 8

Significant decrease in Mn Transport with age in WT mice :

Significant decrease in Mn Transport with age in WT mice Maximal Signal p < 0.05 Time to Smax p < 0.05 Maximal S lope p < 0.01 Time to Vmax p < 0.05 Normalized signal intensity as a function of time

Conclusions:

We show for the first time an early age associated decrease Mn transport in WT (C57B6xSJL) mice while the 5XFAD mice appear to maintain their transport profiles Transport profile for different mouse models needs to be investigated and characterized Future Studies Direct applications in the field of Alzheimer’s disease research Characterization of animal models and establish baseline values Evaluation of treatments during preclinical phase Conclusions

Acknowledgments:

Acknowledgments Wadghiri Lab Anne Bertrand Minh D Hoang Susan Pun Amr Morsi Asad Baig Ben W Little Lindsay K Hill Youssef Z Wadghiri Sigurdsson Lab Pavan Krishnamurthy Hameetha Banu Allal Boutajangout Einar Sigurdsson Turnbull Lab Kamila Szulc Ben Bartelle Cesar Berrios - Otero Makis Parasoglu Giselle Suero - Abreu Helpern Lab Dmitry Novikov Dr Vivian S Lee Orlando Aristizabal Joe Rodriguez Anne Friedland Daniel H Turnbull

authorStream Live Help