Transcript MCB 135K: Discussion

MCB 135K: Discussion
March 9, 2005
GSI: Jason Lowry
Brain Plasticity and
CNS Regenerative Potential
• From the beginning of the 20th Century until the
1990s, it was stated that neurons DID NOT
proliferate.
• The fact that they COULD NOT proliferate did
not exclude the possibility of proliferation under
“specific conditions.”
• In fact, the CNS has a considerable regenerative
potential depending on the special conditions of
the neuronal environment.
Neurons that may proliferate into
adulthood include:
• Progenitor “precursor” neurons lining the
cerebral ventricules
• Neurons in the hippocampus
• Neurons usually “dormant” with potential for
neuron and glia proliferation
• Astrocytes and oligodentrocytes with the ability
to perpetually self renew and produce the three
types of neural cells
Regenerative potential depends on changes in
whole body and neural microenvironment
• Whole body changes:
–
–
–
–
–
–
Physical exercise
Appropriate nutrition
Good circulation
Education
Stress
others
•Neural microenvironment
changes:
–Brain metabolism (oxygen
consumption, free radicals,
circulatory changes)
–Hormonal changes
(estrogens, growth factors,
others)
–others
Mechanisms of Education Effects
Better access to medical care
Better access to recreational activity
Better nutrition
Higher income
Responsibility to health behaviors
No alcohol intake
No smoking
Increased brain reserve capacity?
More dendritic branching, cortical synapses?;
Better cerebral blood flow?;
Better neural cell efficiency, adaptability, redundancy, survival and growth
Evidence from several laboratories show:
• That in the brain there are neural cells which can divide
• These are cells located in:
olfactory bulbs
hippocampus
ependymal cells
(in proximity of the ventricles)
glial cells
(astrocytes which can de-differentiate & differentiate into neurons)
From Wong, R.J., Thung, E., et al., Keeping Cells Young: The role of growth factors in
restricting cell differentiation in cultured neuroglia, FASEB Journal, 17(5): A967, 2003.
Neural Cells
Common ectodermic derivation of neurons and neuroglia
Neural Epithelium
Neuroblast
Neuron
Spongioblast
Migratory Spongioblast
Oligodendrocyte
Astrocyte
• Astrocytes:
– Star shaped cells
– Support neurons metabolically
– Assist in neuronal transmission
• Oligodendrocytes: myelinate neurons
Astrocyte
Ependyma
Growth Curves Measuring Cell
Proliferation
FGF
EGF
Effects of EGF on Neuroglial Cells
Effects of FGF on Neuroglial Cells
600000
1200000
1000000
400000
Control
25 ng/ml
300000
50 ng/ml
100 ng/ml
200000
Number of cells per ml
Number of cells per ml
500000
800000
Control
FGF - 40
600000
FGF - 80
FGF - 160
400000
200000
100000
0
0
0
2
4
6
8
10
12
14
Length of Trial in Days
* Proliferation increased most
effectively with the 50 ng/ml dose
(193% over control cells) for EGF,
reaching a peak at day 10
0
2
4
6
8
10
12
14
Length of Trial in Days
* Proliferation increased most
effectively with the 80 ng/ml dose
(269% over control cells) for FGF,
reaching a peak at day 8
Tsonis, P.A., Stem Cells from Differentiated Cells, Mol. Interven.,4, 81-83, 2004
• From newt amputated limb,
terminally differentiated cells
de-differentiate by losing their
original characteristics. This dedifferentiation produces blastema
cells that then re-differentiate to
reconstitute the lost limb.
• After lentectomy de-differentiated
cells lose pigment and regenerate a
perfect lens.
• De-differentiated myotubes
produce mesenchymal progenitor
cells that are able to differentiate in
adipocytes and osteoblasts.
Also refer to: Brawley, C. and Matunis, E., Regeneration of male germ
line stem cells by spermatogonial de-differentiation in vivo. Science 304,
1331-1334. 2004
Aging of the Visual System
Aging of the Visual System
• Structural Changes (See handout)
– Tear Film:
• Dry eyes or tearing
– Sclera:
• Fat deposits – yellowing
• Thinning – blueing
– Cornea
• Diameter does not change after age 1
• Shape changes
– Retina
• Photoreceptor density decreases; other layers become
disordered
• Illuminance decreases with age
– Lens
• Increased size and thickness
• Becomes more yellow
Aging of the Visual System
• Function
– Corneal and Lens
•
•
•
•
•
Decreased accommodation power
Increased accommodation reflex latency
Refractive error becomes more hyperopic with age
Corneal sensitivity decreases
Scatter increases
– Retinal
•
•
•
•
•
•
•
Decreased critical flicker frequency
Visual acuity declines
Visual Field decreases
Color vision changes
Darkness adaptation is slowed
Increased glare problems
Decreased light reaches retina
Aging of the Visual System
• Recommendation to Accommodate Problems:
–
–
–
–
–
–
–
Wear appropriate optical correction
Increase ambient light
Make lighting even and reduce glare
Improve contrast in critical areas
Avoid rapid changes in light level
Avoid Pastel
Allow more time
Aging of Cardiovascular System
• Atherosclerosis
–
–
–
–
–
–
Characteristics
Disease Results
Arterial Changes
Atherogenesis
Contributing Factors
Age Changes in
Vascular Endothelium
Atherosclerosis
• Characteristics
–
–
–
–
Universal
Progressive
Deleterious
Irreversible …but (?)
Atherosclerosis
• Disease Manifestation
–
–
–
–
Myocardial Infarct
Stroke
Aneurysm
Gangrene
Arterial Changes
• Morphological Characteristics of the Arterial Wall
– Intima – inner most layer of endothelial cells
– Media
•
•
•
•
Elastica interna – formed by elastin fibers
Smooth Muscle cells
Vasa vasorum (penetrates media)
Elastica externa
– Adventitia – outer most layer of collagen bundles
• Vasa vasorum – provide blood
• Read Pages 287-289
Atherogenesis
• Fatty Streak (Intima)
– Increased LDL and oxidized
LDL
– Accumulation of LDL in
endothelial space
– Alter and breakdown of
Elastic fiber
– Alerts immune system
– Monocytes  macrophages
– Phagocytose LDL and
elastic fibers
– Macrophages become full of
LDL and appear as foam
cells after staining
Atherogenesis
• Fibrous Plaque (Intima
and Media)
– Damaged smooth
muscle cells take up
LDL
– Increase foam cells
– Defense mechanism
create scar tissue
– Problem for metabolic
exchange later
Atherogenesis
• Atheroma
– Alteration of
endothelial cells
– Decreased number of
cell
– Platelets seal off area
where there was a loss
of cells
• Increased growth factors
• Increased RBC
• Results in thrombus