Brain (1975) 98, 49-64
TRACE ELEMENT CONCENTRATION IN HUMAN BRAIN ACTIVATION ANALYSIS OF COBALT, IRON, RUBIDIUM, SELENIUM, ZINC, CHROMIUM, SILVER, CESIUM, ANTIMONY AND SCANDIUM
A. HttCK, U. DEMMEL, H. SCHICHA, K. KASPEREK AND L. E. FEINENDEGEN {From the Institute of Medicine, Nuclear Research Centre Mich GmbH, D-517 Mich/Federal Republic of Germany, and the Institute of Anatomy, University of Cologne, D-5000 Cologne/Federal Republic of Germany) TRACE elements are distributed heterogeneously in biological tissues. This was shown by Schicha et al. (1972a) in subcellular structures as well as within macroscopic organ regions. This heterogeneous distribution is recognized to occur in parallel for various essential trace elements and can be interpreted as an expression of functional differences, at a given moment, in different parts of an organ. Specific biochemical reactions and/or structure variations may be involved (Bersin, 1963; Leuthard, 1963; Schiitte, 1965; Schwarz, 1972a). The brain is a particularly suitable organ for correlating trace element distribution to specific function because different regions have specific functions. Previous studies have shown that iron concentration in the brain increases during the first decade and then does not change until at least the age of 74 (Guizetti, 1915; Spatz, 1922a; Sundermann, 1961; Schicha et al., 1971). In this paper, the concentrations of some trace elements are shown to vary specifically in different regions of the human brain and to relate to certain functions associated with these regions. MATERIAL AND METHOD
In the first set of analyses (Group I) tissue samples were dissected from eight denned regions from the corresponding right and left side of six brains of humans aged from 5 hours to 74 years (Table I). In Group II 287 tissue samples were dissected from 7 human brains, the ages ranging from 23 to 60 years (Table I). There was no sign or symptom of disease of the central nervous system in any of the patients. Macroscopic examination of the brains showed no disease; the patients with tumours had no cerebral metastases. Samples were taken twenty to twenty-four hours after death (Table II). The tissue samples were dissected from corresponding sides of the brains with stainless steel instruments and were carefully rinsed with double distilled water. Immediately after dissection the samples were rinsed with double distilled water in order to remove blood contamination. They were then dried in quartz vials for a day at around 110° C. The weights of the dried tissue samples ranged from 10 to 200 mg. The dried samples 4
BRAIN—VOL. XCVm
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BY
50
A. HOCK, U. DEMMEL, H. SCfflCHA, K. KASPEREK AND L. E. FEINENDEGEN
GROUP I
GROUPn
TABLE I . — A G E , SEX AND CAUSE OF DEATH FROM PATIENT A TO M Diagnosis Age Stx 3h M M Congestive heart failure, secondary to congenital feptum defect of atrfam and 4y ventricle 34y C M Congettive heart failure, ncondary to pulmonary hypertension and chronic bronchial asthma D F Rupture of an aortic aneorysm My E F Pulmonary embolism, pelvic vein thrombosis, due to meustatk ca. of vagina 66y 74 y F M Intestinal hsmorrhage, secondary to metastatic ca. of colon
PatUnt A B
K L M
62y 61 y
F F M M
23y 23y 66y
M M M
My 66j
Pulmonary embolism, secondary to mammary ca. Upper respiratory obstruction, secondary to retrostemal goitre Acute myelocytlc leuksmla Arteriosclerotic heart disease and congestive heart failure after surgical removal of ca. of rectum Congenital cardiac malformation, congestive heart failure Circulatory failure following colectomy for ulcerative colitis Arteriosclerotic heart disease, congestive heart failure, ca. of larynx
TABLE n . — T H E DIFFERENT BRAIN REGIONS OF WHICH SAMPLES WERE TAKEN Rethn Groups I II X X (1) Gyrus pracentralis X (2) Gyrus postcentralis (3) Gyrus cuneiformls (4) Gyrus triangularis (3) Gyrus temporalis transversus anterior (6) Gyrus ocdpitalis laterals (7) Cortex around tukus calcarinus (8) Gyrus cingull (?) Centrum semlovale (10) Corpus callosum (11) Cruj fornicil
X X
(12) Nucleus caudatus (13) Putamcn
X X X
(14) Globus pallidus (15) Nucleus anterior thalami (16) Hypothalamus, medial, 0-5 cm below the sulcus hypothalamkus (17) Epiphyni (18) Colliculus rostralis (19) Colliculus caudalis (20)Insula (21) Hippocampus (22) Gyrus dentatus (23)Uncus (24) Corpus amygdaloideum (23) Corpus mamillare (26) Corpus geniculatum laterals (27) Pulvinar thalami (28) Substantia nlgra (29) Nucleus ruber (red nucleus) (30) Cerebellax cortex (31) CerebeUar tonsil (32) Nucleus dentatus cerebelli (33) Nucleus oliraris Inferior
X
X X X X X X X X X X X X X X X X X X X X X X X X X X
X X X
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G H I J
51
TRACE ELEMENTS IN HUMAN BRAIN
were irradiated for ten days in the nuclear research reactor FRJ-1 (KFA Julich) with a thermal neutron flux of approximately 5x 1013 neutrons per cms per sec, the accumulated neutron dose was about 5 x 1019 neutrons per cm8. At various times after activation the gamma-spectra of the samples were registered repeatedly by a germanium-lithium-semiconductor-detector linked to a multi-channel pulse height analyser. The spectra were then analysed by a computer IBM-360/75 (Siller and Kasperek, 1971). This procedure measured the concentration of Co, Fe, Rb, Se,|Zn, Cr, Ag, Cs, Sb and Sc without previous chemical separation. The data were expressed in terms of element weight per unit dried tissue. The relative analytical error amounted to less than 5 per cent for Co, Fe, Rb, Se and Zn and for the other elements up to 20 per cent. RESULTS
TABLE m . — M E A N ABSOLUTE TRACE ELEMENT CONCENTRATIONS IN CEREBRAL CORTEX (A) AND BASAL GANGLIA (B) OF THE BRAINS FROM PATIENTS A TO F WITH STANDARD ERRORS A—Ctrebral Cortex Co 1 0 - ' Fe 1 0 - ' Rb 1 0 - ' Se 1 0 - ' Zn 1 0 - ' Cr 1 0 - ' Ag 1 0 - ' Ci 1 0 - ' Sb 1 0 - ' Sc 10-' Pat. n X 7-86 12-0 2-47 2-86 1-55 0-30 2-35 914 7-64 2-45 8 A 0-50 2-39 0-75 0-97 0-34 0-15 016 0-68 0-50 0-56 sx t 2-21 1-87 1 83 B 2-40 8-38 3-08 0-69 912 33-88 X 7-95 0-27 0-67 019 1-08 0-41 118 1-72 012 0-08 3-79 sx C
8
X sx
2-98 0-20
2-39 017
1-42 Oil
6-73 0-67
4-93 0-46
214 0-31
8-88 2-68
7-70 0-92
2-76 1-29
112 0-61
D
8
X sx
2-18 017
319 Oil
0-63 018
8-70 0-21
6-50 0-46
9-45 1-38
9-54 4-24
4-62 0-41
11-62 2-84
1-97 1-39
E
8
X sx
2-09 0-20
3-08 018
1-32 0-25
7-06 0-50
5-69 0-47
8-89 116
6-58 2-22
6-69 0-36
17-07 814
0-93 0-17
F
8
X sx
4-22 0-29
2-51 0-32
0-60 019
1014 0-28
8-26 0-94
13-49 2-76
495-63 16-28
2-54 0-43
0-25 0-05
44-16 5-72
Fe 10- 4 Rb 10-• 2-23 0-84 0-23 0-08
B—Batal Ganglia Se 1 0 - ' Zn 1 0 - ' Cr 1 0 - ' Ag 1 0 - ' 8-34 6-24 1816 23-38 0-72 0-54 7-01 8-79
Q 1 0 - ' Sb 1 0 - ' 518 8-77 114 405
Sc 1 0 - ' 4-98 1-83
A
8
X sx
Co 10-• 2-69 0-73
B
8
X sx
40-49 819
413 0-32
2-11 0-36
9-03 0-68
9-43 1-22
4-34 0-99
19-50 8-02
314 0-88
2-52 1-55
1-58 0-92
C
8
X
4-25 0 41
7-80 1-31
1-93 0 31
8-06 0-69
5-69 0-34
5-89 0-73
14-43 513
9-38 118
12-36 3-83
1-21 013
ss D
8
X sx
3-78 0-48
7-21 1-08
0-98 0-25
7-93 0-59
6-79 0-67
65-23 18-43
13-41 3-65
5-95 0-87
15-56 4-30
4-74 1-26
E
8
X sx
3-94 0-91
6-39 0-69
2-54 0-45
7-70 0-88
6-38 0-93
161-10 113-29
8-88 2-47
6-68 1-20
18-71 3-59
413 1-17
F
8
X sx
4-60 0-30
7-76 0-74
1-06 0-20
10-38 0-97
8-26 0-95
74-63 46-69
431-88 60-89
2-03 0-56
1 58 1-08
17-36 10-04
x=mean values. S*=standard errors. n=number of samples. It is evident that the concentrations of the essential trace elements Co, Fe, Rb, Se and Zn with the exception of Cr show relatively smaller variations between patients and between regions of the brain than do the concentrations of the non-essential elements.
Downloaded from http://brain.oxfordjournals.org/ at Carleton University on June 11, 2014
Absolute Concentrations of Elements The mean absolute element concentrations from the first group of analyses of cerebral cortex (combined regions 1, 3, 4, 30) and of basal ganglia (combined regions 12, 13, 14, 29) with their standard errors are given in Table ILT.
52
A. HOCK, U. DEMMEL, H. SCfflCHA, K. KASPEREK AND L. E. FEINENDEGEN
TABLE IV.—MEAN ABSOLUTE TRACE ELEMENT CONCENTRATIONS IN THE VARIOUS BRAIN REGIONS FROM PATIENT G TO M WITH STANDARD ERRORS n O. pncccntnlli G. postcentralls Calcerioe cortex HeKhl'i transv. COOT. O. occlp. lot. O. dentatus Hippocampus Uncus Corpus caltosum Eplphysls Nucleus caudatus Putainen PalKdum N. am. thalaml Hypothalamus Corpus genie, lit. Nucleus amygdala Nucleus niger Nucleus rubcr Corpus mamillare Colliculus roatralu Colliculus caudalU Centrum semlovale, white mat. Crus fomicis Pulvinar thalaml Nucleus denutus rnrhfilll Insuia
Co 10- • X Si
13 4-24 0-84 13 360 1-75 14 4-98 0-72 12 4-10 0-61 11 5 03 0-84 7 3-J4 0-58 10 10-28 1-63 13 4-73 0-91 11 1-31 0 1 9 4 7-36 2-78 12 6-07 0-99 10 5-12 1-37 10 4-23 0-93 11 5 1 0 0-82 7 6-03 1-22 11 5-26 1-00 9 3-59 0-61 11 4-32 0-54 11 4 1 9 0-91 11 4-12 0-67 10 3-88 0-63 12 4-38 0-72 4 1-60 0-32 — — 11 5-27 1-08 6 5-40 1-48 3 4-44 0-14
n
Fe 1 0 - i Si X
14 3-28 0-22 13 3-03 0-22 14 3-34 0-1S 12 3-67 0-17 12 4-05 0 1 0 8 2-54 0-25 10 2-38 0 1 9 12 2-36 0 1 4 13 1-23 0 1 2 5 3-62 1-02 12 830 0-46 10 8-78 0-55 9 10-56 0-91 12 3-29 0-32 10 2 1 2 0-16 12 1-66 013 10 2-69 0 1 4 12 810 0-94 11 4-94 0-27 11 4-01 0-39 11 312 0-30 12 2-39 0-17 4 1-31 0-03 2 0 86 0-39 12 3-29 016 6 5-18 0-54 3 2-94 0-10
n 14 13 14 12 12 8 10 13 13 5 12 10 9 12 9 12 10 12 5 11 11 11 4 3 12 6 3
Rb 10- t X s* 113 1-15 1-40 1-62 1-04 1-41 211 1-60 0-85 9-75 2-27 2-63 1-98 1-82 1-54 112 1 54 1-49 115 1-08 1-09 1-19 111 0-73 1-77 1-82 1-97
0-12 011 010 0-11 014 0-25 0-33 0-13 0-08 0-44 013 0-28 0-12 0-24 0-23 015 010 015 0-15 0-10 012 0-18 012 0-07 0-28 0-45 018
n
Se 1 0 - ' X Si
14 7-56 1-04 12 7 1 0 1-02 14 7-51 0-69 12 7-58 0-78 12 8-40 0-91 8 6-38 0-53 10 8-57 0-96 13 7-49 0-68 10 2-83 0-44 4 8-66 3-43 12 8-60 0-83 10 10-93 0-85 10 7-04 0-54 12 9-02 1-19 9 8-49 0-73 11 8-46 2-47 10 7-95 0-56 12 7-47 0-61 11 4-72 0-67 11 7-56 1-07 10 7-32 0-77 12 7-03 0-67 4 312 0 1 2 1 113 12 8-60 0-99 6 718 1-41 3 3-78 1-65
n
Zn 10- • Si X
14 618 l-03| 13 3-92 0-46 14 6-58 0-26 12 6 91 0-51 12 7-54 0-50 3 10-60 1-58 10 9-63 0-47 13 8-83 0-49 13 2-43 0-11 6 22-58 3-81 12 8-63 0-36 10 7-86 0-41 9 5-23 0-35 12 5-98 0-58 10 6-45 0-49 12 4 1 8 0-29 10 7-48 0-46 12 5-86 0-40 11 3-84 0-09 11 5-37 0-29 11 3-94 0-25 12 6 1 6 0-30 4 2-84 0-10 2 2-77 0-48 12 6-52 0-36 6 7-28 1-32 3 9-60 0-37
Downloaded from http://brain.oxfordjournals.org/ at Carleton University on June 11, 2014
A particular finding relates to Fe, which is obviously contained in cerebral cortex and basal ganglia at age-dependent concentrations. Thus, in both cerebral regions Fe concentration is lowest at the earliest age and increases to a plateau beginning after the first decade. Then no significant changes are seen until at least 74 years of age. These data have been previously reported (Schicha et ah, 1971). In addition, the concentration of Rb of the basal ganglia and cerebral cortex appears to vary with age. Unlike Fe, the Rb values appear to decrease steadily from an early age, so that in the eighth decade the Rb content of the brain reaches about half that of the newborn. This diminution with age is obviously greater in the cerebral cortex than in the basal ganglia. The mean values of the non-essential trace element concentrations vary by a factor of up to 75; comparing the single tissue samples within one single brain, differences of more than a factor of 100 are seen. Generally, the values found in the basal ganglia are higher than in the cortex. The mean ratios of essential trace element concentrations of the basal ganglia to the respective cerebral cortex show significant differences for Co, Fe and Rb by factors of 2-43, 1 -40 and 1 -44 respectively. The values for the other elements vary considerably, and the average differences between the concentrations in cerebral cortex and basal ganglia are not statistically significant. From the second group of measurements, the mean numerical values of the concentrations of Co, Fe, Rb, Se and Zn (+standard errors) within the various brain regions are listed in Table IV. In one case (patient G) samples were taken,
TRACE ELEMENTS IN HUMAN BRAIN
53
in addition to the regions mentioned, from the gyms cinguli, nucleus olivaris inferior, and the cerebellar cortex. The concentrations found are not listed in Table IV, but are shown in figs. 1 to 5. The concentrations of the various elements show significant differences between various areas.
TABLE V.—VARIOUS BRAIN SAMPLES GROUPED ACCORDING TO THEIR INVOLVEMENT IN SPECIFIC BRAIN FUNCTION I
Function Ltmbic system (cortex)
n
limbic lystem (nuclei)
m rv
Audition (cortex) Audition (nuclei) Vision (cortex)
VI
VUion (nuclei)
V
vn
Movement (Inhibition)
vm
Movement (facilitation)
DC
Movement (coordination, modulation)
X XI
Movement (voluntary Sensation (limbic system?) Affect Aatonomic system (7) Tracts
xn xm xrv XV XVI
Regioni Gyrus dentatus Hippocampus Uncus Corpus mamillare Corpus amygdaloldeum Nucleus anterior thalwml Gyrus temp, trans, ant. Collicuhis caudalis Cortex around sulcus calcar. Gyms ocdpitalis lateralis Corpus geniculatum laterak Colliculus rostralis* Nucleus caudatus Putamen Globus paUidos Substantia niger Nucleus ruber Nucleus olivaris Inferior Nucleus dentatus cerebeUJ Cerebellar cortex Gyrus pnecentralls Gyrus postcentraHs Insula Gyrus cinguli Hypothalamus Eplphysis Corpus callosum Centrum semiovale Crus fomids
•The colliculus rostralis is grouped with the nuclei because of functional regions, though its histological structure is cortical.
these groupings the values for single trace element concentrations were combined and are graphically listed in figs. 1 to 5. Fig. 1 shows the distribution of Fe in the different functional regions. The cerebral cortical areas (I, m , V, X, XI, XII, Xni), with values between 20 and 40 x 10~5 g per g dried tissue, show only slight differences, but it is conspicuous that the cortical areas of the limbic system show a lower Fe concentration than the nuclei of the limbic system (compare I and II). By contrast the cortical regions of hearing and vision (Til, V) show significantly higher Fe-values than the associated nuclei (TV, VI). A significant Fe load is observed within the motor nuclei with inhibiting
Downloaded from http://brain.oxfordjournals.org/ at Carleton University on June 11, 2014
Trace Element Distribution in Defined Functional Regions of the Brain The various brain regions listed may be grouped according to certain functions to which they are related (Alverdes, 1969; Braus and Elze, 1960; Schneider, 1971). To analyse trace element correlations, the samples were grouped according to their involvement in specific brain functions. This is shown in Table V. According to
[10" B g/g dr.wt]
8
ro
0>
O I
o
oo o
o o
rsi 3
I
w
1
ro en ro
w to
ro [10- B g/g dr.wt.] ro
03
w
H-ro roro tnui
ro
o_ 0)
X
J_JI
Downloaded from http://brain.oxfordjournals.org/ at Carleton University on June 11, 2014
[10- 8 g/g dr.wt.]
TRACE ELEMENT CONCENTRATION IN HUMAN BRAIN ACTIVATION ANALYSIS OF COBALT, IRON, RUBIDIUM, SELENIUM, ZINC, CHROMIUM, SILVER, CESIUM, ANTIMONY AND SCANDIUM
A. HttCK, U. DEMMEL, H. SCHICHA, K. KASPEREK AND L. E. FEINENDEGEN {From the Institute of Medicine, Nuclear Research Centre Mich GmbH, D-517 Mich/Federal Republic of Germany, and the Institute of Anatomy, University of Cologne, D-5000 Cologne/Federal Republic of Germany) TRACE elements are distributed heterogeneously in biological tissues. This was shown by Schicha et al. (1972a) in subcellular structures as well as within macroscopic organ regions. This heterogeneous distribution is recognized to occur in parallel for various essential trace elements and can be interpreted as an expression of functional differences, at a given moment, in different parts of an organ. Specific biochemical reactions and/or structure variations may be involved (Bersin, 1963; Leuthard, 1963; Schiitte, 1965; Schwarz, 1972a). The brain is a particularly suitable organ for correlating trace element distribution to specific function because different regions have specific functions. Previous studies have shown that iron concentration in the brain increases during the first decade and then does not change until at least the age of 74 (Guizetti, 1915; Spatz, 1922a; Sundermann, 1961; Schicha et al., 1971). In this paper, the concentrations of some trace elements are shown to vary specifically in different regions of the human brain and to relate to certain functions associated with these regions. MATERIAL AND METHOD
In the first set of analyses (Group I) tissue samples were dissected from eight denned regions from the corresponding right and left side of six brains of humans aged from 5 hours to 74 years (Table I). In Group II 287 tissue samples were dissected from 7 human brains, the ages ranging from 23 to 60 years (Table I). There was no sign or symptom of disease of the central nervous system in any of the patients. Macroscopic examination of the brains showed no disease; the patients with tumours had no cerebral metastases. Samples were taken twenty to twenty-four hours after death (Table II). The tissue samples were dissected from corresponding sides of the brains with stainless steel instruments and were carefully rinsed with double distilled water. Immediately after dissection the samples were rinsed with double distilled water in order to remove blood contamination. They were then dried in quartz vials for a day at around 110° C. The weights of the dried tissue samples ranged from 10 to 200 mg. The dried samples 4
BRAIN—VOL. XCVm
Downloaded from http://brain.oxfordjournals.org/ at Carleton University on June 11, 2014
BY
50
A. HOCK, U. DEMMEL, H. SCfflCHA, K. KASPEREK AND L. E. FEINENDEGEN
GROUP I
GROUPn
TABLE I . — A G E , SEX AND CAUSE OF DEATH FROM PATIENT A TO M Diagnosis Age Stx 3h M M Congestive heart failure, secondary to congenital feptum defect of atrfam and 4y ventricle 34y C M Congettive heart failure, ncondary to pulmonary hypertension and chronic bronchial asthma D F Rupture of an aortic aneorysm My E F Pulmonary embolism, pelvic vein thrombosis, due to meustatk ca. of vagina 66y 74 y F M Intestinal hsmorrhage, secondary to metastatic ca. of colon
PatUnt A B
K L M
62y 61 y
F F M M
23y 23y 66y
M M M
My 66j
Pulmonary embolism, secondary to mammary ca. Upper respiratory obstruction, secondary to retrostemal goitre Acute myelocytlc leuksmla Arteriosclerotic heart disease and congestive heart failure after surgical removal of ca. of rectum Congenital cardiac malformation, congestive heart failure Circulatory failure following colectomy for ulcerative colitis Arteriosclerotic heart disease, congestive heart failure, ca. of larynx
TABLE n . — T H E DIFFERENT BRAIN REGIONS OF WHICH SAMPLES WERE TAKEN Rethn Groups I II X X (1) Gyrus pracentralis X (2) Gyrus postcentralis (3) Gyrus cuneiformls (4) Gyrus triangularis (3) Gyrus temporalis transversus anterior (6) Gyrus ocdpitalis laterals (7) Cortex around tukus calcarinus (8) Gyrus cingull (?) Centrum semlovale (10) Corpus callosum (11) Cruj fornicil
X X
(12) Nucleus caudatus (13) Putamcn
X X X
(14) Globus pallidus (15) Nucleus anterior thalami (16) Hypothalamus, medial, 0-5 cm below the sulcus hypothalamkus (17) Epiphyni (18) Colliculus rostralis (19) Colliculus caudalis (20)Insula (21) Hippocampus (22) Gyrus dentatus (23)Uncus (24) Corpus amygdaloideum (23) Corpus mamillare (26) Corpus geniculatum laterals (27) Pulvinar thalami (28) Substantia nlgra (29) Nucleus ruber (red nucleus) (30) Cerebellax cortex (31) CerebeUar tonsil (32) Nucleus dentatus cerebelli (33) Nucleus oliraris Inferior
X
X X X X X X X X X X X X X X X X X X X X X X X X X X
X X X
Downloaded from http://brain.oxfordjournals.org/ at Carleton University on June 11, 2014
G H I J
51
TRACE ELEMENTS IN HUMAN BRAIN
were irradiated for ten days in the nuclear research reactor FRJ-1 (KFA Julich) with a thermal neutron flux of approximately 5x 1013 neutrons per cms per sec, the accumulated neutron dose was about 5 x 1019 neutrons per cm8. At various times after activation the gamma-spectra of the samples were registered repeatedly by a germanium-lithium-semiconductor-detector linked to a multi-channel pulse height analyser. The spectra were then analysed by a computer IBM-360/75 (Siller and Kasperek, 1971). This procedure measured the concentration of Co, Fe, Rb, Se,|Zn, Cr, Ag, Cs, Sb and Sc without previous chemical separation. The data were expressed in terms of element weight per unit dried tissue. The relative analytical error amounted to less than 5 per cent for Co, Fe, Rb, Se and Zn and for the other elements up to 20 per cent. RESULTS
TABLE m . — M E A N ABSOLUTE TRACE ELEMENT CONCENTRATIONS IN CEREBRAL CORTEX (A) AND BASAL GANGLIA (B) OF THE BRAINS FROM PATIENTS A TO F WITH STANDARD ERRORS A—Ctrebral Cortex Co 1 0 - ' Fe 1 0 - ' Rb 1 0 - ' Se 1 0 - ' Zn 1 0 - ' Cr 1 0 - ' Ag 1 0 - ' Ci 1 0 - ' Sb 1 0 - ' Sc 10-' Pat. n X 7-86 12-0 2-47 2-86 1-55 0-30 2-35 914 7-64 2-45 8 A 0-50 2-39 0-75 0-97 0-34 0-15 016 0-68 0-50 0-56 sx t 2-21 1-87 1 83 B 2-40 8-38 3-08 0-69 912 33-88 X 7-95 0-27 0-67 019 1-08 0-41 118 1-72 012 0-08 3-79 sx C
8
X sx
2-98 0-20
2-39 017
1-42 Oil
6-73 0-67
4-93 0-46
214 0-31
8-88 2-68
7-70 0-92
2-76 1-29
112 0-61
D
8
X sx
2-18 017
319 Oil
0-63 018
8-70 0-21
6-50 0-46
9-45 1-38
9-54 4-24
4-62 0-41
11-62 2-84
1-97 1-39
E
8
X sx
2-09 0-20
3-08 018
1-32 0-25
7-06 0-50
5-69 0-47
8-89 116
6-58 2-22
6-69 0-36
17-07 814
0-93 0-17
F
8
X sx
4-22 0-29
2-51 0-32
0-60 019
1014 0-28
8-26 0-94
13-49 2-76
495-63 16-28
2-54 0-43
0-25 0-05
44-16 5-72
Fe 10- 4 Rb 10-• 2-23 0-84 0-23 0-08
B—Batal Ganglia Se 1 0 - ' Zn 1 0 - ' Cr 1 0 - ' Ag 1 0 - ' 8-34 6-24 1816 23-38 0-72 0-54 7-01 8-79
Q 1 0 - ' Sb 1 0 - ' 518 8-77 114 405
Sc 1 0 - ' 4-98 1-83
A
8
X sx
Co 10-• 2-69 0-73
B
8
X sx
40-49 819
413 0-32
2-11 0-36
9-03 0-68
9-43 1-22
4-34 0-99
19-50 8-02
314 0-88
2-52 1-55
1-58 0-92
C
8
X
4-25 0 41
7-80 1-31
1-93 0 31
8-06 0-69
5-69 0-34
5-89 0-73
14-43 513
9-38 118
12-36 3-83
1-21 013
ss D
8
X sx
3-78 0-48
7-21 1-08
0-98 0-25
7-93 0-59
6-79 0-67
65-23 18-43
13-41 3-65
5-95 0-87
15-56 4-30
4-74 1-26
E
8
X sx
3-94 0-91
6-39 0-69
2-54 0-45
7-70 0-88
6-38 0-93
161-10 113-29
8-88 2-47
6-68 1-20
18-71 3-59
413 1-17
F
8
X sx
4-60 0-30
7-76 0-74
1-06 0-20
10-38 0-97
8-26 0-95
74-63 46-69
431-88 60-89
2-03 0-56
1 58 1-08
17-36 10-04
x=mean values. S*=standard errors. n=number of samples. It is evident that the concentrations of the essential trace elements Co, Fe, Rb, Se and Zn with the exception of Cr show relatively smaller variations between patients and between regions of the brain than do the concentrations of the non-essential elements.
Downloaded from http://brain.oxfordjournals.org/ at Carleton University on June 11, 2014
Absolute Concentrations of Elements The mean absolute element concentrations from the first group of analyses of cerebral cortex (combined regions 1, 3, 4, 30) and of basal ganglia (combined regions 12, 13, 14, 29) with their standard errors are given in Table ILT.
52
A. HOCK, U. DEMMEL, H. SCfflCHA, K. KASPEREK AND L. E. FEINENDEGEN
TABLE IV.—MEAN ABSOLUTE TRACE ELEMENT CONCENTRATIONS IN THE VARIOUS BRAIN REGIONS FROM PATIENT G TO M WITH STANDARD ERRORS n O. pncccntnlli G. postcentralls Calcerioe cortex HeKhl'i transv. COOT. O. occlp. lot. O. dentatus Hippocampus Uncus Corpus caltosum Eplphysls Nucleus caudatus Putainen PalKdum N. am. thalaml Hypothalamus Corpus genie, lit. Nucleus amygdala Nucleus niger Nucleus rubcr Corpus mamillare Colliculus roatralu Colliculus caudalU Centrum semlovale, white mat. Crus fomicis Pulvinar thalaml Nucleus denutus rnrhfilll Insuia
Co 10- • X Si
13 4-24 0-84 13 360 1-75 14 4-98 0-72 12 4-10 0-61 11 5 03 0-84 7 3-J4 0-58 10 10-28 1-63 13 4-73 0-91 11 1-31 0 1 9 4 7-36 2-78 12 6-07 0-99 10 5-12 1-37 10 4-23 0-93 11 5 1 0 0-82 7 6-03 1-22 11 5-26 1-00 9 3-59 0-61 11 4-32 0-54 11 4 1 9 0-91 11 4-12 0-67 10 3-88 0-63 12 4-38 0-72 4 1-60 0-32 — — 11 5-27 1-08 6 5-40 1-48 3 4-44 0-14
n
Fe 1 0 - i Si X
14 3-28 0-22 13 3-03 0-22 14 3-34 0-1S 12 3-67 0-17 12 4-05 0 1 0 8 2-54 0-25 10 2-38 0 1 9 12 2-36 0 1 4 13 1-23 0 1 2 5 3-62 1-02 12 830 0-46 10 8-78 0-55 9 10-56 0-91 12 3-29 0-32 10 2 1 2 0-16 12 1-66 013 10 2-69 0 1 4 12 810 0-94 11 4-94 0-27 11 4-01 0-39 11 312 0-30 12 2-39 0-17 4 1-31 0-03 2 0 86 0-39 12 3-29 016 6 5-18 0-54 3 2-94 0-10
n 14 13 14 12 12 8 10 13 13 5 12 10 9 12 9 12 10 12 5 11 11 11 4 3 12 6 3
Rb 10- t X s* 113 1-15 1-40 1-62 1-04 1-41 211 1-60 0-85 9-75 2-27 2-63 1-98 1-82 1-54 112 1 54 1-49 115 1-08 1-09 1-19 111 0-73 1-77 1-82 1-97
0-12 011 010 0-11 014 0-25 0-33 0-13 0-08 0-44 013 0-28 0-12 0-24 0-23 015 010 015 0-15 0-10 012 0-18 012 0-07 0-28 0-45 018
n
Se 1 0 - ' X Si
14 7-56 1-04 12 7 1 0 1-02 14 7-51 0-69 12 7-58 0-78 12 8-40 0-91 8 6-38 0-53 10 8-57 0-96 13 7-49 0-68 10 2-83 0-44 4 8-66 3-43 12 8-60 0-83 10 10-93 0-85 10 7-04 0-54 12 9-02 1-19 9 8-49 0-73 11 8-46 2-47 10 7-95 0-56 12 7-47 0-61 11 4-72 0-67 11 7-56 1-07 10 7-32 0-77 12 7-03 0-67 4 312 0 1 2 1 113 12 8-60 0-99 6 718 1-41 3 3-78 1-65
n
Zn 10- • Si X
14 618 l-03| 13 3-92 0-46 14 6-58 0-26 12 6 91 0-51 12 7-54 0-50 3 10-60 1-58 10 9-63 0-47 13 8-83 0-49 13 2-43 0-11 6 22-58 3-81 12 8-63 0-36 10 7-86 0-41 9 5-23 0-35 12 5-98 0-58 10 6-45 0-49 12 4 1 8 0-29 10 7-48 0-46 12 5-86 0-40 11 3-84 0-09 11 5-37 0-29 11 3-94 0-25 12 6 1 6 0-30 4 2-84 0-10 2 2-77 0-48 12 6-52 0-36 6 7-28 1-32 3 9-60 0-37
Downloaded from http://brain.oxfordjournals.org/ at Carleton University on June 11, 2014
A particular finding relates to Fe, which is obviously contained in cerebral cortex and basal ganglia at age-dependent concentrations. Thus, in both cerebral regions Fe concentration is lowest at the earliest age and increases to a plateau beginning after the first decade. Then no significant changes are seen until at least 74 years of age. These data have been previously reported (Schicha et ah, 1971). In addition, the concentration of Rb of the basal ganglia and cerebral cortex appears to vary with age. Unlike Fe, the Rb values appear to decrease steadily from an early age, so that in the eighth decade the Rb content of the brain reaches about half that of the newborn. This diminution with age is obviously greater in the cerebral cortex than in the basal ganglia. The mean values of the non-essential trace element concentrations vary by a factor of up to 75; comparing the single tissue samples within one single brain, differences of more than a factor of 100 are seen. Generally, the values found in the basal ganglia are higher than in the cortex. The mean ratios of essential trace element concentrations of the basal ganglia to the respective cerebral cortex show significant differences for Co, Fe and Rb by factors of 2-43, 1 -40 and 1 -44 respectively. The values for the other elements vary considerably, and the average differences between the concentrations in cerebral cortex and basal ganglia are not statistically significant. From the second group of measurements, the mean numerical values of the concentrations of Co, Fe, Rb, Se and Zn (+standard errors) within the various brain regions are listed in Table IV. In one case (patient G) samples were taken,
TRACE ELEMENTS IN HUMAN BRAIN
53
in addition to the regions mentioned, from the gyms cinguli, nucleus olivaris inferior, and the cerebellar cortex. The concentrations found are not listed in Table IV, but are shown in figs. 1 to 5. The concentrations of the various elements show significant differences between various areas.
TABLE V.—VARIOUS BRAIN SAMPLES GROUPED ACCORDING TO THEIR INVOLVEMENT IN SPECIFIC BRAIN FUNCTION I
Function Ltmbic system (cortex)
n
limbic lystem (nuclei)
m rv
Audition (cortex) Audition (nuclei) Vision (cortex)
VI
VUion (nuclei)
V
vn
Movement (Inhibition)
vm
Movement (facilitation)
DC
Movement (coordination, modulation)
X XI
Movement (voluntary Sensation (limbic system?) Affect Aatonomic system (7) Tracts
xn xm xrv XV XVI
Regioni Gyrus dentatus Hippocampus Uncus Corpus mamillare Corpus amygdaloldeum Nucleus anterior thalwml Gyrus temp, trans, ant. Collicuhis caudalis Cortex around sulcus calcar. Gyms ocdpitalis lateralis Corpus geniculatum laterak Colliculus rostralis* Nucleus caudatus Putamen Globus paUidos Substantia niger Nucleus ruber Nucleus olivaris Inferior Nucleus dentatus cerebeUJ Cerebellar cortex Gyrus pnecentralls Gyrus postcentraHs Insula Gyrus cinguli Hypothalamus Eplphysis Corpus callosum Centrum semiovale Crus fomids
•The colliculus rostralis is grouped with the nuclei because of functional regions, though its histological structure is cortical.
these groupings the values for single trace element concentrations were combined and are graphically listed in figs. 1 to 5. Fig. 1 shows the distribution of Fe in the different functional regions. The cerebral cortical areas (I, m , V, X, XI, XII, Xni), with values between 20 and 40 x 10~5 g per g dried tissue, show only slight differences, but it is conspicuous that the cortical areas of the limbic system show a lower Fe concentration than the nuclei of the limbic system (compare I and II). By contrast the cortical regions of hearing and vision (Til, V) show significantly higher Fe-values than the associated nuclei (TV, VI). A significant Fe load is observed within the motor nuclei with inhibiting
Downloaded from http://brain.oxfordjournals.org/ at Carleton University on June 11, 2014
Trace Element Distribution in Defined Functional Regions of the Brain The various brain regions listed may be grouped according to certain functions to which they are related (Alverdes, 1969; Braus and Elze, 1960; Schneider, 1971). To analyse trace element correlations, the samples were grouped according to their involvement in specific brain functions. This is shown in Table V. According to
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