Transcript Higher education

Regeneration, Repair, and
Plasticity
Chapters 6, 7, 8, 10
P.S. Timiras
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
• Neuroglia (astrocytes, oligodentrocytes) and
microglia (immune cells) 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
Death Rates in 1986 among Persons 25- 64 Years Old in Selected
Education and Income Groups According to Race and Sex.
________________________________________________________
Group
White
Men
Black
Women
Men
Women
deaths per 1000
Education- yr
Completed
School
0-11
12
College
1-3
4
7.6
4.3
3.4
2.5
4.3
2.8
2.1
1.8
5.0
6.0
3.2
2.2
Income-$
<9,000
9,000-14,999
15,000-18,999
19,000-24,999
>25,000
16.0
10.2
5.7
4.6
2.4
6.5
3.4
3.3
3.0
1.6
19.5
10.8
9.8
4.7
3.6
7.6
4.5
3.7
2.8
2.3
13.4
8.0
6.2
3.9
______________________________________________________________________________________
Pappas, G., Queen, S., Hadden, W., and Fisher, G. The increasing disparity in mortality between socioeconomic groups in the United
States, 1960 and 1986. N. Engl. J Med. 329, 103-109, 1993.
Proportion of Remaining Life Expected to be Lived with a Disability in
Activities of Daily Living and Death Rates
________________________________________________________
At Age
65
At Age
75
At Age
85
Death Rates
per 1,000
White men
Low education
.11
Higher education .10
.21
.19
.45
.37
7.6
2.8
White women
Low education
.15
Higher education .14
.24
.23
.45
.40
3.4
1.8
Black men
Low education
.13
Higher education .11
.22
.18
.36
.31
13.4
6.0
Black women
Low education
.15
.22
.36
6.2
Higher education .14
.21
.31
2.2
________________________________________________________________________
From: Guralink, J.M., et al., Educational status and active life expectancy among older blacks and whites, N Engl. J Med., July 8,
1993, Vol. 29:110-116
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
Fig. 7-4: “Denudation” of the neurons. Changes in
pyramidal neurons of the aging human cerebral cortex
Anatomical Correlates of Educational Protective Effects*
Educational Level
Anatomical Correlate
Increasing levels from <12 to >12
grades
total dendritic length
mean dendritic length
dendritic segment count
Location
Pyramidal cells in layer 2,3 of
Wernicke’s area
Variable Studied
Gender
Hemisphere
Education
Personal history
Hormonal Correlate
Thyroid Hormones
Glucocorticoids
______________
* From Jacobs et al., J Comp. Nuerol., 327, 97, 1993
dendritic number and length
reactive synaptogenesis
Table 3 -7 Percent of Perso ns 7 0 Years of Age and Older
who Report Spe ci fic Con ditio ns
as a C ause of Limit atio n in Act ivitie s of Daily Livin g:
Unit ed St ate s, 1995
Type of Condition
Art hritis
Heart disease
Stroke
Respirato ry
Diabetes
Percent
10.6
4.0
2.6
2.5
1.5
From t he1994 National Health Interview Survey , Second Suppleme nt on
Agin g, Centers for Disease Cont rol and Preventi on, National Center for
Health Stati stics
Perceived Functioning of Medicare Beneficiaries, by Gender and Age, 2002
100
Perform with difficulty
65-74 years
80
75-84 years
85 years and over
60
40
20
0
Women
Men
Mobility Limitation
Women
Men
ADL
Women
IADL
Source: Health & Health Care of the Medicare Population: Data from the 2002 Medicare Current
Beneficiary Survey. Rockville, MD: Westat, February 2006
Men
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
Neuroglial 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
Assays of enzymatic activity
(e.g. glutamine synthetase--a marker of
astrocytes)
show decreased activity
suggesting a loss of astrocytic specificity
From:
•
Proliferation
•Maturation
To:
•
Proliferation
•De-differentiation
Astrocyte
“Activated”
astrocyte
Proliferating
astrocytes
Neuroblast
migrate
From: Doetsch, F., et al., Neuron, 36:1021, 2002.
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
de-differentiation produces
blastema cells that then redifferentiate to reconstitute
the lost limb.
• After lentectomy dedifferentiated 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
Get Up and Move:
A Call to Action
for Older Men & Women
The brain regulates motor function
and, reciprocally,
Motor function influences brain activity
Throughout life,
One’s behavior can change the structure of the brain
And these changes
Can affect how we behave in our environment
Additional Studies
• To promote regeneration/repair
responses in aging muscle:
– Injection of growth hormone in aging
cardiac muscle
– Implantation of stem cells into
infarcted cardiac muscle