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Stress and Exercise Effects on Neuroplasticity

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Augustus Chang

on 4 May 2015

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Transcript of Stress and Exercise Effects on Neuroplasticity

Transgenic regulation of BMP signaling mirrors effects of exercise on SGZ niche cell lineage properties
Cidu/Idu = Cell Division
Sox2/DCX = Young Growing Neurons
Stress and Exercise Effects on Neuroplasticity
-Integral roles in memory formation and navigational spatial memory
-Important regions: CA3 (Cornu Ammonis) and Dentate Gyrus (DG)

Negative emotions: aggression, fear, and anxiety
Important region: BLA (Basolateral Amygdala)

Synaptic Remodeling:
Changes in neuronal pathways
Changes in synaptic strength
Due to:
behavior, environment, neural processes, thinking, emotions, insult (injury), entire metabolic processes
Synaptic Plasticity
Animals: Adult male Wistar rats
Stress protocol: Chronic Immobilization Stress (CIS) and Acute Immobilization Stress (AIS)
Corticosterone Measurements
Body Weight Measurements
Tissue Collection and BDNF Measurements
Materials and Methods
Chronic stress elicits opposite effects on BDNF levels in the BLA and area CA3
Recovery after chronic stress fails to reverse elevated levels of BDNF in the BLA, but not in area CA3
Augustus Chang, Ron Clearie, Dan Kerrigan, Shaan Sadhwani
What is plasticity?
What causes plasticity?
Where does it occur?
Why do you care?

Acute stress also differs in its impact on BDNF expression over time in the BLA and area CA3
Neuron Anatomy

Neural Stem Cells
Implicated in learning and memory
Neural Stem Cells
Located in 2 areas of brain
Subgranular Zone (SGZ) of the hippocampus - Dentate Gyrus (DG)
Neural Stem Cells
Correlation between number of new neurons and learning/memory
Correlation between learning new tasks and number of new neurons
Irradiation of neural stem cells results in impaired learning
BMP and Noggin
Bone Morphogenic Protein (BMP) known to promote neural stem cells differentation to astrocytic lineage
Noggin is BMP antagonist
More BMP = More astrocytes, Less neurons
More Noggin = Less BMP = More neurons, Less astrocytes
Shown to promote neurogenesis
Shown to enhance learning and memory
What we know:
1) Chronic stress causes an increase in BLA (amygdala) BDNF
-What behavioral change might one expect?
2) Chronic stress causes a decrease in CA3 (Hippocampus) BDNF
-What behavioral change might one expect?
What we know after 1 day

1)Chronic stress causes an increase in BLA BDNF
2) Chronic stress causes a decrease in CA3 BDNF
What we know after 21 days
1) Mice BDNF levels will return to normal in CA3
2)Mice BDNF levels will have increased by 21 days
Acute stress works a little different
-CA3 BDNF levels will initially drop but then return to normal after recovery
-BLA BDNF levels will rise but will not continue to increase after recovery
How can you tell when a mouse is actually stressed?
Elective exercise decreases BMP4 and increases noggin expression in the
More exercise = Higher Cognition
More exercise = More Noggin, Less BMP
Does this necessarily mean higher levels of noggin and lower levels of BMP cause higher cognition?
- Indicated connection between BMP regulation and cell proliferation
-Showed that both exercise and decreased BMP/increased Noggin can independently alter neurogenesis
- Correlated role of BMP signaling itself to neurogenesis in the hippocampus

BMP Signaling regulates cognitive performance on hippocampus-dependent behavioral and memory tasks
-These tests demonstrated the specificity of BMP signaling on aspects of cognition related to the hippocampus
- Y -Maze indicated spatial working memory
-Novel Object indicated recall ability

What did we learn today?
-Exercise stimulates neurogenesis and increased cognitive function in the hippocampus - i.e plasticity
-BMP Signaling plays a direct role in the mediation of this effect
-Reductions in BMP signaling via Noggin enable the effects of exercise

"Correlation does not imply causation."
HPA Axis (Hippocampal-Pituitary-Adrenal Axis)
Chronic Stress
What is BDNF?
10 Days

1 Day Later
Recovery Period
21 Days

Acute Stress
1 Day

1 Day Later

Recovery Period

10 Days Later

(Samples Taken)
Take Homes:
Amygdala Growth
Hippocampal Growth
Hippocampus Recovers to normal faster than Amygdala
Its a signaling protein
Stress = Hippocampus Size = BDNF

Stress = Amygdala Size = BDNF
Study of Expression at the Cellular Level
What we know:
-Exercise changes BMP/Noggin Levels
- Increase Noggin and Decrease BMP
-Exercise improves Cognition
What do we want to see?
- Based on changes in the levels of noggin or BMP specifically(taking out the exercise factor) look for:
Increased or decreased cell growth and same change in cognition
Confirm that changes in BMP itself are responsible for changes in the hippocampus

- Defined as genetically altering mice so that they express a protein regardless of a stimulus(exercise in this case)
- Mice that express BMP at high levels
- Mice that express Noggin at high levels
- Control: Wild Type mice that have not been altered
How? - Making Transgenic Mice
Next Step

- Use the transgenic mice to test aspects of learning and memory that are dependant on the hippocampus
- Spatial Learning and Recall
- What do we expect to find?
- Mice that express BMP showed less cell divison and growth
- Should have lowered cognitive ability
- Mice that express Noggin showed greater cell division and growth
-Show have increased cognitive ability
Behavioral test of cognitive ability
Cognitively intact mouse should show a tendency to enter a less recently visited arm
The number of arm entries recorded in order to calculate the percentage of alternation
Wild Type: Not Altered
Red Mice: Noggin
Blue Mice: BMP
Wild Type
Experimental Groups
6 Groups of mice each given access to a running wheel for different periods of time (0, 2, 4, 7, 10, 14 days)
Mice then underwent Y-Maze test to determine level cognition
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