Transcript Aging of the Nervous System: Structural Changes

Aging of the Nervous
System:
Structural Changes
Chapters 7, 8, 9
PS 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
Major Function of the
Nervous System
The major function of the CNS is to
communicate & to connect:
•with other CNS cells
•with peripheral tissues (outside CNS)
•with the external environment (including
physical and social environments)
Major Function of
the Nervous System, II
This communication regulates:
•Mobility
•Sensory information
•Cognition
•Affect and mood
•Functions of whole-body systems
Cogito Ergo Sum
“ I think, therefore I am”
-René Descartes (1596-1650)
Figure 3.2: Comparison of the
relationship of brain weight to life
span in vertebrates
Each neuron
has, on
average,
10,000
connections
ranging from
a few
thousand to
over
100,000.
The number of glial cells is 10-15x that of
neurons.
Fig. 7-4: “Denudation” of the neurons. Changes in
pyramidal neurons of the aging human cerebral cortex
In normal aging, the loss of
neurons is moderate & occurs in
specific brain areas:
 Locus ceruleus (catecholaminergic
neurons)
 Substantia nigra (dopaminergic
neurons)
 Nucleus basalis of Meynert
(cholinergic neurons)
 Hippocampus (cholinergic neurons)
Young
Fig. 7-6: Neuron
from 605 day old
rat
Old
Fig. 7-5: Free radical accumulation
(lipofuscin) in young rats and old rats
Fig. 7-7:
Magnification of
lipofuscin
granules of Fig.
7-6
C
A & B: Fibrillary tangles
Alterations of tau
protein and microtubule
assembly? Paired Helical
Filaments (PHF)
C: Neuritic plaque
Accumulation of amyloid
broken down PHFs
Fig. 7-8: Lewy Bodies. Aggregation of filaments,
vesicular profiles and poorly resolved granular
material
Pathological and Cellular
Changes with Normal Aging
 Increased intracellular deposits of
lipofuscin
 Intracellular formation of PHFs
 Accumulation of amyloid deposits in
the neuritic plaques and
surrounding the cerebral blood
vessels
 Accumulation of Lewy bodies
 Cell death (apoptosis, necrosis)
Fig. 7-1: Diagram of electrophysiological,
functional, and chemical sites for
changes in the brain with aging
Fig. 7-11: Diagrams
of established
CNS synapses
illustrating
presynaptic
synthesis,
storage,
metabolism,
synaptic release,
and postynaptic
binding.
See Table 7.2 Page 108
See Table 7.3 Page 109
For more details on
Neurotransmitters and
Synaptic Function
Acetylcholinesterase Inhibition
Presynaptic
nerve terminal
Muscarinic
receptor
Postsynaptic
nerve
terminal
Nordberg A, Svensson A-L. Drug Safety. 1998;19:465-480.