Regeneration, Repair, and Plasticity (continued) Chapters 6, 7, 8, 10 P.S. Timiras.
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Regeneration, Repair, and Plasticity (continued)
Regeneration, Repair, and Plasticity (continued)
Chapters 6, 7, 8, 10P.S. Timiras
Anatomical Correlates of Educational Protective Effects*Educational Level Increasing levels from <12 to >12
grades
Anatomical Correlate total dendritic length
mean dendritic length
dendritic segment count
Location Pyramidal cells in layer 2,3 of Wernicke’s area
Variable Studied GenderHemisphereEducationPersonal history
Hormonal Correlate Thyroid Hormones dendritic number and length Glucocorticoids reactive synaptogenesis ______________* From Jacobs et al., J Comp. Nuerol., 327, 97, 1993
Evidence from several laboratories show: That in the brain there are neural cells which can
divideThese are cells located in:
olfactory bulbshippocampus
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.
Common ectodermic derivation of neurons and neuroglia
Astrocytes:Star shaped cellsSupport neurons metabolicallyAssist in neuronal transmission
Oligodendrocytes: myelinate neurons
Neural Epithelium
Neuroblast Spongioblast
Neuron Migratory Spongioblast Astrocyte Ependyma
Oligodendrocyte Astrocyte
Neural Cells
Growth Curves Measuring Neuroglial Cell Proliferation
Effects of FGF on Neuroglial Cells
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Control
FGF - 40
FGF - 80
FGF - 160
Effects of EGF on Neuroglial Cells
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25 ng/ml
50 ng/ml
100 ng/ml
EGF FGF
* Proliferation increased most effectively with the 50 ng/ml dose (193% over control cells) for EGF, reaching a peak at day 10
* 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”
astrocyteProliferating
astrocytes Neuroblast
migrate
From: Doetsch, F., et al., Neuron, 36:1021, 2002.
Blue: DAPI (stains nucleus)Red: NeuN (a neuronal marker)
Untreated glia EGF treated glia FGF treated glia
Control: Neurons
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 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
Muscle cellsMuscle cells• Muscle cells, like neurons,
– do not usually divide– do not regenerate after
trauma/damage/old age.• This is interpreted as a
decline in regeneration/specific signaling.
• Special cells -- satellite cells -- act as myocyte’s progenitor cells.– When exposed to a young
systemic milieu, these cells upregulate specific genes and successfully regenerate/repair the damaged old tissue.
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 changesCan affect how we behave in our environment
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