- Email: [email protected]
Respiration and aerobic glycolysis in rat cerebral cortex during postnatal maturation. Influence of hypothyroidism
Life Sciences Vol. 3, pp. 979-986, 1964. Pergamon Press, Inc. Printed in the United States.
RESPIRATION AED AEROBIC CLYCOLYSIS IN BAT CEBEBBAL CORTEX DURING POSTNATAL MATURATION.INFLUENCE OF HYPOTHYROIDISM Nora E. Chittoni (+) and Carlos J. C&e& Departamento de Bioqufmioa,Facultad de Fawaoia Bioquimioa,Universidad de Buenos Aires
y
(Received 7 July 1964) Neonatal hypothyroidism in rats, produoes several morphological ohanges in the oerebral cortex (l-3) as well as modifioations in the electrical pattern (4) and in the activity of certain enzymes
(5). It
has also been shown that the postnatal maturation of the rat cortex, is correlated with a marked increase in respiration and aerobic glycolysis (6, 7). The present investigation was therefore undertaken to find cut the effects of thyroid deffioiency, induced shortly after birth, upon the in vitro oxygen and glucose uptake and lactate formation by oerebra1
cortex
slioes
measured in an isc-osmotio medium, as well as to
study the stimulatory action of a high concentration of potassium on respiration and aerobic glycolysis. Methods Bats of the Wistar strain were used troughcut this work. New born rats were made hypothyroid by a single intraperitoneal injeotion of 1OOpc
I 131, according to Goldberg and Chaikoff (8).
Normal control and injected rats were kept with their mothers until the 20th
day of life, being fed "ad libitum" after that date. Bio-
ohemical determinations were carried out with animals of both groups, at 4 days intervals, until the 20th
day of life ; similar measurements were
(+) Fellow, Consejo National de Investigaoiones Cientfficas y Tdonioas Argentina.
979
980
FtESPIEtATION AND AEROBIC GLYCOLYSIS
Vol.
3, No. 9
also oarried out in normal oontrol and injeoted rats 30 and 40 days old, and only with adults of the oontrol group (100-150days old, 185-285 g body weight). After deoapitation,the brains were quiokly removed and 0.5 mm thiok slices of oerebral oorter were prebared aooording to Yajno and bunker (9). They were immediatelyweighed and washed in a pre-chilled inoubationmedium without gluoose. Subsequently,the slices were introduoed into ohilled Warburg vessels oontaining 2 ml
of the following
inoubationmedium: 115 mMBaCl; 5 LUM KCl; 1.8 mH CaC12 ; 1.3 mb!lAgsO 1 4 mW KH2P04 ; 33 IINTris Buffer pH 7.41 and 3.3 mW gluoose. In experiments In whioh the effect of potassium was studied, the concentration of KC1 was inoreased by 100 mM. The vessels were gassed 5 minutes with oxygen, and after 10 minutes of equilibration,the rate of oxygen uptske was meaeured manometrically at 37OC, by the standardWarburg prooedure, at 10 minutes intervals, during 60 minutes. At the end of this period, the vessels wera removed from their manometers, and quioklg oooled in an ioe-bath,and samples for gluoose and laotate determinationswere pipetted into triahloroaoetlo aoid solution (lC$ final oonoantration).Gluoose was determined aooordlng to G6mee and Gris (10) and laotate by the method of Barker and tierson
(11). Gluoose uptake and laotate formationware oaloulated
by the dlfferenoa of oonoantrationin the medium before and after the lnoubationperiod. Results In the injected group of animals, histologioalexaminationof tha anterior
neok region showed oomplata destruotionof the thyroid gland.
Body waight inareaeed vary slowly in theee rats after the 20th day of life (fig. 1). Brain weight wan lowar than In nomal
oontrols,
although
th4
differenoerae not so markad ae for body -d&t* Table 1 shore the 0hang44 in oryg4n uptake, gluooee utilisation
snd
laotate formation in elioes lnoubated in an ieo-osmotiomedium. In tha oortex of hypothyroidrate, tha oqrgen uptake wa4 found to ba at all tiw4
Vol.
RESPIRATION
3, No. 9
4
8
42
16
AND AEROBIC GLYCOLYSIS
20
40
0 = body weight A-
___ -
brain weight
981
- normal rats - hypothyroidrats
FIG. 1 Variationsin B-odyand Brain Weight of Normel and HypothyroidFLats,During Postnatal Development
B
k
I
160
e
30
The results are given as per cent of the rate In leo-osmotiomedium. 0 normal rats5 mhypothyroid rats. FIG. 2 Potassium Stimulationof Oxygen Uptake (A) and Laotate Formation (B) in Cerebral Cortloal Slloee
982
RESPIRATIONANDAEROBICGLYCOLYSIS
Vol. 3, No. 9
TABLE 1
Oqgen and Gluoose Uptake, and Laotate Formation in Cortioal Cerebral Slioee from Normal (N) and Hypothyroid (H) Eats, Inoubated in an Iso-oamotioMedium. OXYGEN
GLUCOSE
UPTAKE
UPTAKE
FOIKATIOIO
a
35.3 2 1.6
22.1 + 1.5
25.4 ,+1.8
H
34.3 + 3.8
23.4 ,+2.7
20.0 + 4.2
'
40.2 f:3.4
18.7 2 4.6
14.1 2 3.1
H
37.1 i:2.7
16.9 2 2.5
14.0 2 3.1
N
56.5 + 2.1
20.1 + 3.5
18.6 ,+3.4
H
41.4 + 2.5
15.9 2 1.6
15.2
AGE
DAYS 4
8
12
LACTATE
2 3.0
p
16
N
64.0 f 2.9
20.6 + 1.2
16.5 + 2.0
H
51.3 + 3.8
16.8 2 2.4
14.5 2 3.4
p (0.02
20
B
63.3 +,2.6
24.1 2 2.8
16.0 2.3.5
H
50.4 2 3.2
18.3 + 3.2
16.5 +,4.0
p - 0.02 30
40
ADULTS
F
65.6 +,3.1
21.2 ?.2.9
13.8 + 5.3
H
62.9 +,0.4
21.1 t 2.2
14.5 + 1.9
B
77.1 +,1.3
24.2 +,1.7
23.4 +,1.9
H
70.7 + 4.1
24.8 + 1.3
26.7 2 2.8
B
66.6 +,5.0
21.8 i:1.0
15.2
2 1.6
The results are given in)Imoleeper gram of fresh tiemue and per houk; they are the meana of 6 determinationsf standard error. P ie the probability oalaulatod on the baeis of the t value; when P ie not indioated, there ia not aieifioant differenoe. smaller than in their littermateoontrole.However the differenoeswere mtatiatioallyeignifioantonly between the 12th and 20th days of life. Gluoom uptake and laotate formationwere not modified by thyroideotomy. These rewrite led ua to eeleot 8, 20 and 30 daye aa the age to
Vol. 3, No. 9
983
RESPJRATIONANDAEROBICGLYCOLYSIS
study the stimU18tOq effeot of 8 high OOnO0ntr8tiOnof pOt8ssiUl.Table 2 abows that oxyen uptake by the oortex of hypothyroidrate, inoubatsd in 8 105 fi
KC1
medium, w8s 81W8ys signifioentlylower than that observed
in the Oontrols. C1uOose uptake snd l8Ot8te formation showed 8 signifiO8nt
TABLE2 Oxygen 8nd Qluoose Uptake, and kLOt8te Formation Of COrtiO8l Cerebral Slioes from Normal (y) and Hypothyroid (H) Bats, Inoubatedin 105 mM KC1 Medium. AGE DAYS
8
20
30
OXYCiEU UPTAKE
OLUCOSE UPTAKE
B
52.8% 2.9
33.8+- 1.6
30.4+- 1.9
H
32.9 +, 1.0
15.8 +, 1.0
15.9 +, 0.9
p (0.01
p (0.ca1
p (0.01'
N
94.7 +, 3.5
37.0% 3.8
41.3 t 2.3
H
54.6 +, 1.2
24.7 +, 0.7
25.8 +, 0.7
p(o.001
P (0.05
p (0.01
B
96.0 +, 3.1
31.7 +, 1.9
41.3 +, 4.0
H
70.1: 3.0
36.1+- 1.7
41.7 +, 1.8
LACTATE FWMATIOD
p (0.01
Values expressed as in Table 1.
deorease at 8 and 20 days, but not at 30 days. Fig. 2 shows the stimulationof respiration8nd glyoolysisby pota+ sium in norPla1snd hypothyroidrats. In the latter, the oxygen uptake is not significantlyinoreased but the 1aotate formationis stimulated,re8ohing the levels of normal stimulatedrat cortex at 30 days. Discussion Our results show that oxygen uptake of the rat brain oortex, inoubec ted in an iso-osmotiomedium, inoreases slowly during the firet 8 days of life, and muoh faster between 8-16 daye, reaohing adult levels at 16 deys of life. The IIIaxi0n.m rate in laotate formation ooours in 4 dsys old rats. These results agree with those reported by other investigstors(6, 12)
RESPIRATION
984
AND AEROBIC GLYCOLYSIS
Vol.
3, No. 9
and oan be correlated with the time of appearanoe of spontaneous electrical activity in the rat brain (13, 14). In hypothyroid animals between 12 to 20 days of life, there is a very signifioant decrease in oxygen uptake, while at 30-40 days, the differences with the oontrols are not significant. These findings may be explained by a delay in the maturation process produced by the lack of thyroid hormone. Eayrs (4) h as explained in a similar way the delayed appearanoe.of eleotrioal aotivity in the brain cortex of hypothyroid rats. Our results on the stiuulation of respiration and glycolysis by a hi&
conoentration of potassium in normal rats, show that it inoreases
with the age of the animal, reaching adult levels between 20-30 days. These results are in agreement with those of Greengard and YoIlwain (7) who observed a similar effect by applying eleotrical pulses to slices of the cortex during the first 40 days of life. The oxygen uptake of hypothyroid rats is not stimulated by potassium, furthermore laotate fornlationis less stimulated than in the oontrols at 8-20 days, and it is equal to oontrols of 30 days. The qeohanism by whioh a high concentration of potassium inoreases respiration and gluoose metabolism,
is
still not well known. The aotion
of potassium ie similar, but not equal, to the effect of eleotrical pulses. It
is
possible that both produce a depolarization of neuronal membranes
and inorease the aoetyl-ooenzyme A formation, the rate of which limits the whole process of gluoose utilization (15). The differenoee in reponses to a high oonoentration of potassium by the hypothyroid rat brain oortex could be explained by: a) a delayed maturation of the neuronal membrane, oorrelated with hypoplaetic dendrites and a reduoed number of axons available for axo-dendritio synapeie in the hypothyroid brain oorter (4)~ b) a delayed mitoohondrial maturation in hypothyroid brain oorter. Although further work ie neoessary to explain these findings, it is nevertheless interesting to point cut that hypothyroidism and malonate
RESPIRATION AND AEROBIC GLYCOLYSIS
Vol. 3, No. 9 (16) produoe
985
similar effects on the respirationof the oortex stimulated
by potassium without alterationof the glyoolysis.On the other hand, it is known that experimentalhypothyroidismleads to a substantialdepression of suooinio dehydrogenaseaotivity (5) and to a deorease in the levels of amino aoids of the glutemic group (17).All these findings, toðer with the results described in the present paper, are suggestive of an unknown change in the function of mitoohondriain the hypothyroid brain. Aoknowledmnts This work has been supportedby Grant B" 287 of the
National
Multiple Solerosis Sooiety (USA) and by Grant B" 1003 of the Consejo Raoionsl de InvestigaoionesCientifioasy Tdonioas (Argentina).We wish also to th8nk Professor Moises Polak for oarring out the histologio8l oontrols.
Referenoes
160 (1955).
1.
J.T.RAYRS, Aota Anat.Basel.2&
2.
J.T.EAYRS, and W.A.LtSlDUH,
3.
J.T.EAYBS, and B.GOODHEAD,J.Anat.London &,
4.
J.T.BAYBS, in "The Structure and Punotion of Cerebral Cortex"(Ed.by
Brit.J.Anim.Behav.1, 17 (1955).
D.B.TOWEB, and J.P.SCHADE) p.43,
385 (1959).
Elsevier Pub.Co.,Betherlands(1955).
5.
Y.HAMWJRG, and L.B.FLEKREB,J.Reuroohem.&
279 (1957).
6.
P.MARDEL, R.BILTH, and J.D.WEILL, in "Metabolismof the Nervous System"(Ed.byD.RICHTRB)p.291, Pergemon Prese, London (1957).
7.
P.GRBENGARD,and H.MoILWAIB,in "Bioohemistryof the Developing &NOUS
&tteItI"
(Bd.by H.WAELSH) p.251, Academia Press, Bea York,
(1955). 8.
R.C.GOIDBEBG,ana I.L.CHAIKOFF,Endoorinolom 41, 64 (1949). -
9.
O.MAJBO, and W.B.mEB,
J.Beuroohem.3
11 (1957).
986
10.
RESPIRATION
C.J.GOXE&
AND AEROBIC
Vol.
GLYCOLYSIS
3, No.
and M.R.GRIS, Revista Sooiedad Argentina Bioloda
9
2, -
276 (1954). 535 (1941).
11.
S.B.BARKER, and W.E.SUMMERSON, J.Biol.Chem.
12.
P.S.TIMIRAS, J.A.MOGUILEVSKY, and S.CERL, in 2nd.Internat.Symp. on "Effect of Ionizing Radiation on Nervous System",Los Aqeles
(1963).
In press. 1, 705 (1957).
13.
W.A.HIYWICH, J.A.C.PETERSEN, and Y.L.ALLEN, Neurolow
14.
W.A.HIMWICH, 1nternat.Rev.Neurobiolog.v 4, 117 (1962).
15.
N.N.KINI, and J.H.QUASTBL, Nature
16.
G.TAKAGAKI, S.HIRANO, and Y.TSUKA.DA,J.Bioohem.Japan & -
17.
A.RAMIREX, and C.J.GOMEZ, unpublished data.
184, 252 (1959). 41 (1958).
RESPIRATION AED AEROBIC CLYCOLYSIS IN BAT CEBEBBAL CORTEX DURING POSTNATAL MATURATION.INFLUENCE OF HYPOTHYROIDISM Nora E. Chittoni (+) and Carlos J. C&e& Departamento de Bioqufmioa,Facultad de Fawaoia Bioquimioa,Universidad de Buenos Aires
y
(Received 7 July 1964) Neonatal hypothyroidism in rats, produoes several morphological ohanges in the oerebral cortex (l-3) as well as modifioations in the electrical pattern (4) and in the activity of certain enzymes
(5). It
has also been shown that the postnatal maturation of the rat cortex, is correlated with a marked increase in respiration and aerobic glycolysis (6, 7). The present investigation was therefore undertaken to find cut the effects of thyroid deffioiency, induced shortly after birth, upon the in vitro oxygen and glucose uptake and lactate formation by oerebra1
cortex
slioes
measured in an isc-osmotio medium, as well as to
study the stimulatory action of a high concentration of potassium on respiration and aerobic glycolysis. Methods Bats of the Wistar strain were used troughcut this work. New born rats were made hypothyroid by a single intraperitoneal injeotion of 1OOpc
I 131, according to Goldberg and Chaikoff (8).
Normal control and injected rats were kept with their mothers until the 20th
day of life, being fed "ad libitum" after that date. Bio-
ohemical determinations were carried out with animals of both groups, at 4 days intervals, until the 20th
day of life ; similar measurements were
(+) Fellow, Consejo National de Investigaoiones Cientfficas y Tdonioas Argentina.
979
980
FtESPIEtATION AND AEROBIC GLYCOLYSIS
Vol.
3, No. 9
also oarried out in normal oontrol and injeoted rats 30 and 40 days old, and only with adults of the oontrol group (100-150days old, 185-285 g body weight). After deoapitation,the brains were quiokly removed and 0.5 mm thiok slices of oerebral oorter were prebared aooording to Yajno and bunker (9). They were immediatelyweighed and washed in a pre-chilled inoubationmedium without gluoose. Subsequently,the slices were introduoed into ohilled Warburg vessels oontaining 2 ml
of the following
inoubationmedium: 115 mMBaCl; 5 LUM KCl; 1.8 mH CaC12 ; 1.3 mb!lAgsO 1 4 mW KH2P04 ; 33 IINTris Buffer pH 7.41 and 3.3 mW gluoose. In experiments In whioh the effect of potassium was studied, the concentration of KC1 was inoreased by 100 mM. The vessels were gassed 5 minutes with oxygen, and after 10 minutes of equilibration,the rate of oxygen uptske was meaeured manometrically at 37OC, by the standardWarburg prooedure, at 10 minutes intervals, during 60 minutes. At the end of this period, the vessels wera removed from their manometers, and quioklg oooled in an ioe-bath,and samples for gluoose and laotate determinationswere pipetted into triahloroaoetlo aoid solution (lC$ final oonoantration).Gluoose was determined aooordlng to G6mee and Gris (10) and laotate by the method of Barker and tierson
(11). Gluoose uptake and laotate formationware oaloulated
by the dlfferenoa of oonoantrationin the medium before and after the lnoubationperiod. Results In the injected group of animals, histologioalexaminationof tha anterior
neok region showed oomplata destruotionof the thyroid gland.
Body waight inareaeed vary slowly in theee rats after the 20th day of life (fig. 1). Brain weight wan lowar than In nomal
oontrols,
although
th4
differenoerae not so markad ae for body -d&t* Table 1 shore the 0hang44 in oryg4n uptake, gluooee utilisation
snd
laotate formation in elioes lnoubated in an ieo-osmotiomedium. In tha oortex of hypothyroidrate, tha oqrgen uptake wa4 found to ba at all tiw4
Vol.
RESPIRATION
3, No. 9
4
8
42
16
AND AEROBIC GLYCOLYSIS
20
40
0 = body weight A-
___ -
brain weight
981
- normal rats - hypothyroidrats
FIG. 1 Variationsin B-odyand Brain Weight of Normel and HypothyroidFLats,During Postnatal Development
B
k
I
160
e
30
The results are given as per cent of the rate In leo-osmotiomedium. 0 normal rats5 mhypothyroid rats. FIG. 2 Potassium Stimulationof Oxygen Uptake (A) and Laotate Formation (B) in Cerebral Cortloal Slloee
982
RESPIRATIONANDAEROBICGLYCOLYSIS
Vol. 3, No. 9
TABLE 1
Oqgen and Gluoose Uptake, and Laotate Formation in Cortioal Cerebral Slioee from Normal (N) and Hypothyroid (H) Eats, Inoubated in an Iso-oamotioMedium. OXYGEN
GLUCOSE
UPTAKE
UPTAKE
FOIKATIOIO
a
35.3 2 1.6
22.1 + 1.5
25.4 ,+1.8
H
34.3 + 3.8
23.4 ,+2.7
20.0 + 4.2
'
40.2 f:3.4
18.7 2 4.6
14.1 2 3.1
H
37.1 i:2.7
16.9 2 2.5
14.0 2 3.1
N
56.5 + 2.1
20.1 + 3.5
18.6 ,+3.4
H
41.4 + 2.5
15.9 2 1.6
15.2
AGE
DAYS 4
8
12
LACTATE
2 3.0
p
16
N
64.0 f 2.9
20.6 + 1.2
16.5 + 2.0
H
51.3 + 3.8
16.8 2 2.4
14.5 2 3.4
p (0.02
20
B
63.3 +,2.6
24.1 2 2.8
16.0 2.3.5
H
50.4 2 3.2
18.3 + 3.2
16.5 +,4.0
p - 0.02 30
40
ADULTS
F
65.6 +,3.1
21.2 ?.2.9
13.8 + 5.3
H
62.9 +,0.4
21.1 t 2.2
14.5 + 1.9
B
77.1 +,1.3
24.2 +,1.7
23.4 +,1.9
H
70.7 + 4.1
24.8 + 1.3
26.7 2 2.8
B
66.6 +,5.0
21.8 i:1.0
15.2
2 1.6
The results are given in)Imoleeper gram of fresh tiemue and per houk; they are the meana of 6 determinationsf standard error. P ie the probability oalaulatod on the baeis of the t value; when P ie not indioated, there ia not aieifioant differenoe. smaller than in their littermateoontrole.However the differenoeswere mtatiatioallyeignifioantonly between the 12th and 20th days of life. Gluoom uptake and laotate formationwere not modified by thyroideotomy. These rewrite led ua to eeleot 8, 20 and 30 daye aa the age to
Vol. 3, No. 9
983
RESPJRATIONANDAEROBICGLYCOLYSIS
study the stimU18tOq effeot of 8 high OOnO0ntr8tiOnof pOt8ssiUl.Table 2 abows that oxyen uptake by the oortex of hypothyroidrate, inoubatsd in 8 105 fi
KC1
medium, w8s 81W8ys signifioentlylower than that observed
in the Oontrols. C1uOose uptake snd l8Ot8te formation showed 8 signifiO8nt
TABLE2 Oxygen 8nd Qluoose Uptake, and kLOt8te Formation Of COrtiO8l Cerebral Slioes from Normal (y) and Hypothyroid (H) Bats, Inoubatedin 105 mM KC1 Medium. AGE DAYS
8
20
30
OXYCiEU UPTAKE
OLUCOSE UPTAKE
B
52.8% 2.9
33.8+- 1.6
30.4+- 1.9
H
32.9 +, 1.0
15.8 +, 1.0
15.9 +, 0.9
p (0.01
p (0.ca1
p (0.01'
N
94.7 +, 3.5
37.0% 3.8
41.3 t 2.3
H
54.6 +, 1.2
24.7 +, 0.7
25.8 +, 0.7
p(o.001
P (0.05
p (0.01
B
96.0 +, 3.1
31.7 +, 1.9
41.3 +, 4.0
H
70.1: 3.0
36.1+- 1.7
41.7 +, 1.8
LACTATE FWMATIOD
p (0.01
Values expressed as in Table 1.
deorease at 8 and 20 days, but not at 30 days. Fig. 2 shows the stimulationof respiration8nd glyoolysisby pota+ sium in norPla1snd hypothyroidrats. In the latter, the oxygen uptake is not significantlyinoreased but the 1aotate formationis stimulated,re8ohing the levels of normal stimulatedrat cortex at 30 days. Discussion Our results show that oxygen uptake of the rat brain oortex, inoubec ted in an iso-osmotiomedium, inoreases slowly during the firet 8 days of life, and muoh faster between 8-16 daye, reaohing adult levels at 16 deys of life. The IIIaxi0n.m rate in laotate formation ooours in 4 dsys old rats. These results agree with those reported by other investigstors(6, 12)
RESPIRATION
984
AND AEROBIC GLYCOLYSIS
Vol.
3, No. 9
and oan be correlated with the time of appearanoe of spontaneous electrical activity in the rat brain (13, 14). In hypothyroid animals between 12 to 20 days of life, there is a very signifioant decrease in oxygen uptake, while at 30-40 days, the differences with the oontrols are not significant. These findings may be explained by a delay in the maturation process produced by the lack of thyroid hormone. Eayrs (4) h as explained in a similar way the delayed appearanoe.of eleotrioal aotivity in the brain cortex of hypothyroid rats. Our results on the stiuulation of respiration and glycolysis by a hi&
conoentration of potassium in normal rats, show that it inoreases
with the age of the animal, reaching adult levels between 20-30 days. These results are in agreement with those of Greengard and YoIlwain (7) who observed a similar effect by applying eleotrical pulses to slices of the cortex during the first 40 days of life. The oxygen uptake of hypothyroid rats is not stimulated by potassium, furthermore laotate fornlationis less stimulated than in the oontrols at 8-20 days, and it is equal to oontrols of 30 days. The qeohanism by whioh a high concentration of potassium inoreases respiration and gluoose metabolism,
is
still not well known. The aotion
of potassium ie similar, but not equal, to the effect of eleotrical pulses. It
is
possible that both produce a depolarization of neuronal membranes
and inorease the aoetyl-ooenzyme A formation, the rate of which limits the whole process of gluoose utilization (15). The differenoee in reponses to a high oonoentration of potassium by the hypothyroid rat brain oortex could be explained by: a) a delayed maturation of the neuronal membrane, oorrelated with hypoplaetic dendrites and a reduoed number of axons available for axo-dendritio synapeie in the hypothyroid brain oorter (4)~ b) a delayed mitoohondrial maturation in hypothyroid brain oorter. Although further work ie neoessary to explain these findings, it is nevertheless interesting to point cut that hypothyroidism and malonate
RESPIRATION AND AEROBIC GLYCOLYSIS
Vol. 3, No. 9 (16) produoe
985
similar effects on the respirationof the oortex stimulated
by potassium without alterationof the glyoolysis.On the other hand, it is known that experimentalhypothyroidismleads to a substantialdepression of suooinio dehydrogenaseaotivity (5) and to a deorease in the levels of amino aoids of the glutemic group (17).All these findings, toðer with the results described in the present paper, are suggestive of an unknown change in the function of mitoohondriain the hypothyroid brain. Aoknowledmnts This work has been supportedby Grant B" 287 of the
National
Multiple Solerosis Sooiety (USA) and by Grant B" 1003 of the Consejo Raoionsl de InvestigaoionesCientifioasy Tdonioas (Argentina).We wish also to th8nk Professor Moises Polak for oarring out the histologio8l oontrols.
Referenoes
160 (1955).
1.
J.T.RAYRS, Aota Anat.Basel.2&
2.
J.T.EAYRS, and W.A.LtSlDUH,
3.
J.T.EAYBS, and B.GOODHEAD,J.Anat.London &,
4.
J.T.BAYBS, in "The Structure and Punotion of Cerebral Cortex"(Ed.by
Brit.J.Anim.Behav.1, 17 (1955).
D.B.TOWEB, and J.P.SCHADE) p.43,
385 (1959).
Elsevier Pub.Co.,Betherlands(1955).
5.
Y.HAMWJRG, and L.B.FLEKREB,J.Reuroohem.&
279 (1957).
6.
P.MARDEL, R.BILTH, and J.D.WEILL, in "Metabolismof the Nervous System"(Ed.byD.RICHTRB)p.291, Pergemon Prese, London (1957).
7.
P.GRBENGARD,and H.MoILWAIB,in "Bioohemistryof the Developing &NOUS
&tteItI"
(Bd.by H.WAELSH) p.251, Academia Press, Bea York,
(1955). 8.
R.C.GOIDBEBG,ana I.L.CHAIKOFF,Endoorinolom 41, 64 (1949). -
9.
O.MAJBO, and W.B.mEB,
J.Beuroohem.3
11 (1957).
986
10.
RESPIRATION
C.J.GOXE&
AND AEROBIC
Vol.
GLYCOLYSIS
3, No.
and M.R.GRIS, Revista Sooiedad Argentina Bioloda
9
2, -
276 (1954). 535 (1941).
11.
S.B.BARKER, and W.E.SUMMERSON, J.Biol.Chem.
12.
P.S.TIMIRAS, J.A.MOGUILEVSKY, and S.CERL, in 2nd.Internat.Symp. on "Effect of Ionizing Radiation on Nervous System",Los Aqeles
(1963).
In press. 1, 705 (1957).
13.
W.A.HIYWICH, J.A.C.PETERSEN, and Y.L.ALLEN, Neurolow
14.
W.A.HIMWICH, 1nternat.Rev.Neurobiolog.v 4, 117 (1962).
15.
N.N.KINI, and J.H.QUASTBL, Nature
16.
G.TAKAGAKI, S.HIRANO, and Y.TSUKA.DA,J.Bioohem.Japan & -
17.
A.RAMIREX, and C.J.GOMEZ, unpublished data.
184, 252 (1959). 41 (1958).