Presentation made by Dr. Orly Lazarov at the Alzheimer Research Forum Live Webinar of March 20, 2013 - http://www.alzforum.org/res/for/journal/detail.asp?liveID=209

1. Effects of the environmental model depend on:
1. Experimental (animal) model
2. Type of intervention: enrichment, running, toys etc.
3. Duration
4. Age of animals
5. Gender

2. Environmental Enrichment:
1. Multiple effects= multiple signaling pathways?
1. If multiple pathways- do they all lead to the same
downstream effect?
3. If not, how do we identify the critical signal(s)?

3. Amelioration of pathology: Reduced amyloidosis in FAD transgenic
mice following an enriched environment
Standard Housing Enriched
Hippocampus
Cortex
Cortex Hippocampus
25
Relative level (Arbitrary Units)
Relative level (Arbitrary Units)
25
20
20
15 * 15
**
10 10
5 5
0 0
Standard Housing Enriched
Standard Housing Enriched

4. Amelioration of pathology: Reduced tau hyperphosphorylation in
FAD transgenic mice following an enriched environment
25 20
FL-APP (Arbitrary Units)
Tau5 (Arbitrary Units)
Hippocampus 20
15
15
Standard Housing Enriched 10
10
5
5
FLAPP
0 0
SH EN SH EN
Tau5 40 40
PHF1 (Arbitrary Units)
KHC (Arbitrary Units)
30 30
PHF1
20 20
KLC 10 10
0 0
KHC SH EN SH EN
30 20
Actin (Arbitrary Units)
Actin KLC (Arbitrary Units) 15
20
10
10
5
0 0
SH EN SH EN

5. Enhanced Cell Proliferation and neuronal differentiation in the dentate gyrus of
APPswe/PS1ΔE9 mice following environmental enrichment
* vs. nonTg SH Standard Housing Enrichment
8000 ** vs. APP/PS1 SH
*
NonTg
Total BrdU+ cells
6000 **
4000
APPSwe/PS1ΔE9
2000
0
NonTg APP/PS1
* vs. nonTg SH
Standard Housing
4000 ** vs. APP/PS1 SH Enriched BrdU/DCX
* **
BrdU+/DCX+ cells
3000
2000
1000
0
NonTg APP/PS1

6. More New Neurons in the dentate gyrus of
APPswe/PS1ΔE9 mice following environmental enrichment
800
* vs. Nontg SH BrdU/NeuN/GFAP
** vs. APP/PS1 SH
BrdU+/NeuN+ cells
**
600
*
400
200
0
NonTg APP/PS1
* vs. nonTg SH Standard Housing
500 ** vs. APP/PS1 SH Enriched
* ** BrdU/GFAP BrdU/S100β
BrdU+/GFAP+ cells
400
300
200
100
0
NonTg APP/PS1

7. Hippocampal LTP is enhanced following environmental enrichment

8. Does EE affect mainly the
hippocampus?

9. Increased connectivity between CA1 and cortical areas in FAD-linked mice
Following environmental enrichment
Regions that correlated with the extracted
time-course from left CA1 and right CA1 for
each individual animal.
Spin echo anatomical reference T1 weighted images
acquired in the coronal plane.
Molecularly mediated by cognition-associated signals
Little, Foxely and Lazarov, J Alz Dis, 2012