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PHYSIOLOGICAL CHANGES
OF THE CENTRAL NERVOUS
SYSTEM IN ELDERLY
Ginus Partadiredja
The Department of Physiology
Faculty of Medicine UGM
Learning Objectives
1. To understand the anatomical changes of the central
nervous system in elderly
2. To understand the physiological changes of the central
nervous system in elderly
THEORIES OF AGEING
Ageing What?
Why?
How?
5. Neuroendocrine Hypotheses
6. Neuroendocrine-immuno Hypothesis
FIG. 1. Production of oxygen and nitrogen free radicals and other reactive species in mammalian cells. AA, amino acid; Arg, L-arginine; BH4,
(6R)-5,6,7,8,-tetrahydro-L-biopterin; CH2O, formaldehyde; Cit, L-citrulline; DQ, diquat; ETS, electron transport system; FAD, flavin adenine
dinucleotide (oxidized); FADH2, flavin adenine dinucleotide (reduced); Gly, glycine; H2O2, hydrogen peroxide; HOCl, hypochlorous acid;
H•LOH, hydroxy lipid radical;IR, ionizing radiation; L•, lipid radical; LH, lipid (unsaturated fatty acid); LO•, lipid alkoxyl radical; LOO•, lipid peroxyl
radical; LOOH, lipid hydroperoxide;MPO, myeloperoxidase; NAD, nicotinamide adenine dinucleotide (oxidized); NADH, nicotinamide adenine
dinucleotide (reduced); NADP, nicotinamide adenine dinucleotide phosphate (oxidized); NADPH, nicotinamide adenine dinucleotide phosphate
(reduced); •NO, nitric oxide; O2, superoxide anion radical; •OH, hydroxyl radical; ONOO, peroxynitrite; P-450, cytochrome P-450; PDG,
phosphate-dependent glutaminase; Sar, Sarcosine; SOD, superoxide dismutase; Vit C, vitamin C; Vit E, vitamin E (-tocopherol).
FIG. 2. Removal of oxygen and nitrogen free radicals and other reactive species in mammalian cells. ADP, adenosine diphosphate; Arg, arginine;
BH4, (6R)-5,6,7,8,-tetrahydro-L-biopterin; Carn, carnosine; Cat, catalase; Cit, citrulline; Cyt C, cytochrome C; ETS, electron transport system; Glu,
L-glutamate; Gly, glycine; -Glu-CySH, -glutamyl-cysteine; GS-SG, oxidized glutathione (glutathione disulfide); GSH, glutathione (reduced form);
GSH-Px, glutathione peroxidases; GSH-R, glutathione reductase; GSH-T, glutathione S-transferase; GSNO, nitrosylated glutathione; HbO2,
oxyhemoglobin; Heme-NO, heme-nitric oxide; His, histidine; LOH, lipid alcohol; LOO•, lipid peroxyl radical; LOOH, lipid hydroperoxide; •NO, nitric
oxide; NO3, nitrate; O2, superoxide anion radical; ONOO, peroxynitrite; PC, pentose cycle; R•, radicals; R, non-radicals; R5P, ribulose 5-
phosphate; SOD, superoxide dismutase; Tau, taurine; Vit C, vitamin C (ascorbic acid); Vit C•, vitamin C radical; Vit E, vitamin E (-tocopherol); Vit
E•, vitamin E radical.
MEMORY
Types of Memory
• Explicit spatial memory (in rats)
• Episodic (events)
• Semantic (words, rules, language)
• Implicit
• Non-associative (single stimulus)
• Habituation
• Sensitization
• Associative (the relation of one stimulus to another)
• Classic conditioning
• Operant conditioning
• Skills & habits
• Priming (facilitation of recognition of objects by prior
exposure; recall word when presented first few letters)
Explicit memory:
- associated with awareness
- easily formed & easily forgotten
- hippocampus & medial temporal lobes (entorhinal cortex,
perirhinal cortex, parahippocampal cortex)
- can be converted into implicit memory (e.g. athlete training)
Implicit memory:
- does not involve awareness
- requires repetitive practice, longer time to form & store, but
not easily forgotten
- hippocampus; striatum (basal ganglia), cerebellum
- Skills (riding a bicycle, tying shoes, playing piano), habits,
conditioned reflexes
AGEING IN THE CENTRAL NERVOUS SYSTEM
• Effects of ageing on memory related to hippocampus
and medial temporal lobe structure variable among
individuals
• On average, explicit memory declines with age, but
marked variability occurs
• Spatial memory (explicit memory) in rats declines with
age (as measured in Morris water maze test), but variable
• Recognition memory declines with age in monkeys, but
variable
Morris water maze test
Neurobiology of Age-Related Memory Decline
Hippocampal Physiology
• Hippocampal physiology is affected selectively:
• Not affected:
• Resting potential, input resistance, amplitude &
duration of evoked potentials
• Percentage of neurons for location-specific firing &
spatial selectivity of place fields
• Affected:
• Intensity & frequency of stimulation required for LTP
(long-term potentiation) increase with age
• LTP decays more rapidly in aged subjects (rapid
forgetting)
• Long-term depression (LTD) changes
• Informational content of place (confuse familiar
environments sharing certain stimulus elements)
• Hippocampal encoding increasingly rigid (more
prevalent in the CA3 field than CA1)
Figure 2. A three-dimensional
organisation of the septo-
hippocampal system in the rat
brain. The hippocampus is the C-
shaped structure. Abbreviations: fx
= fornix; fi = fimbria; HC =
hippocampus; MS = medial septum
(modified from Amaral and Witter
1995).
CA1
CA2 S
ML
CA3 H GL
Treatment B
Volume = 2 units
Nv = 10/2
=5 Volume = 0,5 units
Nv = 10/ 0,5
= 20
The advent of Unbiased Stereology
• Methods in unbiased stereology:
• Physical disector hippocampus
• Physical fractionator
• Optical disector
• Optical fractionator hippocampus
• Single disector or ‘cheating disector’
• Double disector
• ‘Molecular’ or ‘golden’ disector average number of
molecules per cell in biological sections
A bv
prefrontal lobe