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Biomedical subjects

A Nehlig

Publications and source records attributed to A Nehlig.

At least 127 records · Page 7Linked to original sources

Local cerebral glucose utilization in normal female rats: variations during the estrous cycle and comparison with males.

The quantitative 2-[14C]deoxyglucose autoradiographic method was used to study the fluctuations of energy metabolism in discrete brain regions of female rats during the estrous cycle. A consistent though statistically nonsignificant cyclic variation in average glucose utilization of the brain as a whole was observed. Highest levels of glucose utilization occurred during proestrus and metestrus, whereas lower rates were found during estrus and diestrus. Statistically significant fluctuations were found specifically in the hypothalamus and in some limbic structures. Rates of glucose utilization in the female rat brain were compared with rates in normal male rats. Statistically significant differences between males and females at any stage of the estrous cycle were confined mainly to hypothalamic areas known to be involved in the control of sexual behavior. Glucose utilization in males and females was not significantly different in most other cerebral structures.

Animals↗

Effects of acute administration of caffeine on local cerebral glucose utilization in the rat.

The quantitative 2-[14C]deoxyglucose autoradiographic method was used to study the effects of acute intravenous injections (15 min prior to study) of caffeine on brain energy metabolism. With doses of 0.1 mg/kg the effects of caffeine on cerebral glucose utilization were limited to the habenula, spinal trigeminal and paraventricular nuclei. After the 1.0 mg/kg dose significant increases were additionally seen in the caudate, ventral tegmental area and medial septum. After the injection of 10 mg/kg of caffeine, average glucose utilization of the brain as a whole was increased by 15%, and of 71 structures examined 31 structures were statistically significantly affected. Among these were all brainstem monoaminergic cell groupings, components of the extrapyramidal motor system, anterior cingulate, and medial prefrontal cortex. In the hypothalamus glucose utilization increased only in the paraventricular nucleus, arcuate nucleus, and median eminence. This study demonstrates that there is a correlation between the known stimulant effects of caffeine on behavior and widespread increases in glucose utilization throughout the brain.

Animals↗

Activity of acetoacetyl--CoA thiolase and regulation of ketone body metabolism in the brain of the developing chick.

The acetoacetyl-CoA thiolase activity was estimated in subcellular fractions isolated from the cerebral hemispheres, the optic lobes and the cerebellum of the chick between the 20th day of embryonic life and the 30th day of postnatal maturation. Acetoacetyl-CoA thiolase is located both in mitochondria and microsomes of the chick brain. Mitochondrial enzyme activity remains high between the 20th day of embryonic life and the 2nd or the 4th day after hatching, depending on the considered brain area. It then decreases until 30 days after hatching. Cytoplasmic thiolase activity remains unchanged during pre- and postnatal development in the cerebral hemispheres; it increases during the same time in the optic lobes. In the cerebellum, cytoplasmic thiolase activity develops in the same way as in mitochondria. The regulation of ketone body utilization by the developing chick brain widely differs from that by the mammalian brain. In the chick, 3-hydroxybutyrate is nearly the single ketone body utilized by the brain. It is converted into acetyl-CoA in the mitochondria and cytoplasm of the chick brain through two exactly parallel pathways involving the participation of the same enzymes.

Acetyl-CoA C-Acetyltransferase↗

Activities of 3-oxo acid-CoA transferase and acetoacetyl-CoA synthetase in brain and liver of the developing chick.

The 3-oxo acid-CoA transferase and acetoacetyl-CoA synthetase activities were estimated in subcellular fractions isolated from the cerebral hemispheres, the optic lobes, the cerebellum and the liver of the chick between the twentieth day of embryonic life and the thirtieth day of postnatal development. In the 3 areas of chick brain, the transferase activity increases during the whole postnatal development. Transferase is located both in mitochondria and microsomes unlike in the rat brain where this enzyme is specifically mitochondrial. There is no detectable activity of synthetase in the chick brain. These differences in enzyme localization imply that acetoacetate is converted into acetoacetyl-CoA only by 3-oxo acid-CoA transferase in the mitochondria and cytoplasm of the chick brain, whereas, in the rat brain, this reaction is performed by 3-oxo acid-CoA transferase in mitochondria and by acetoacetyl-CoA synthetase in the cytosol. There is no detectable activity either for transferase or for synthetase in the chick liver.

Aging↗

Variations of 3-hydroxybutyrate dehydrogenase activity in brain and liver mitochondria of the developing chick.

1. The 3-hydroxybutyrate dehydrogenase activity was estimated in the crude mitochondrial fraction isolated from the cerebral hemispheres, the optic lobes, the cerebellum and the liver of the chick between the 20th day of embryonic life and the 30th day of postnatal maturation. 2. The optimal conditions of liberation and of determination of 3-hydroxybutyrate dehydrogenase activity were studied in the mitochondrial fraction isolated from chick cerebral hemispheres and liver. 3. The subcellular distribution of the enzyme in the chick brain and liver is very different from that in the rat. 3-Hydroxybutyrate dehydrogenase is completely mitochondrial in the rat brain and liver whereas in the chick brain and liver, it is located in mitochondrial and microsomal fractions; moreover, a third component can even be found in the soluble fraction of chick liver. 4. The 3-hydroxybutyrate dehydrogenase activity reaches the same value in the three areas of 20-day-old chick embryo brain. Between this stage and the 4th day after hatching, it increases to reach the same peak in the three areas. This peak however, appears at different stages according to the considered brain area. At 30 days after hatching, the enzyme activity is higher in the cerebellum than in the cerebral hemispheres and optic lobes. 5. The activity of hepatic 3-hydroxybutyrate dehydrogenase is 10 to 20 times lower than in the brain. It does not significantly change between 1 day before and 4 days after hatching and increases 2-fold between 4 and 30 days after hatching. 6. The variations of 3-hydroxybutyrate dehydrogenase activity in chick brain indicate correlations of this enzyme activity with development, particularly related to the nutritional state of the chicks. The fairly important differences in the activity of 3-hydroxybutyrate dehydrogenase in the liver of the chick and the rat enable us to come to a better understanding of the regulation of the concentration of the different ketone bodies in the blood of the chick and the rat. Moreover, the presence of the microsomal component of 3-hydroxybutyrate dehydrogenase in chick brain probably originates in the low concentration of acetoacetate in chick blood.

Animals↗

Ultrastructural and biochemical studies of the swelling of developing chick telencephalic slices.

An ultrastructural and biochemical study of the importance and localization of tissue swelling was performed on telencephalic slices of 1- and 30-day-old chicks incubated in an oxygenated or a non-oxygenated physiological medium. The swelling of slices is greater for 30-day-old chick material than for that from 1-day-old chicks. It also reaches higher values in the non-oxygenated than in the oxygenated medium. When the 30-day-old chick telencephalic slices are incubated in an oxygenated medium, swelling mainly affects astrocytes, and especially the astrocytic endfeet. When they are incubated in a non-oxygenated medium, the astrocytes and astrocytic endfeet are very swollen and in addition the swelling also affects the neurons and their organelles. Extracellular space is increased. When 1-day-old chick telencephalic slices are incubated in a non-oxygenated medium, the tissue structures are well preserved. Swelling predominantly affects astrocytes and astrocytic endfeet. Neurons are not affected and the extracellular space is reduced. However, when they are incubated in an oxygenated medium, tissue structures are greatly affected showing a high degree of disorganization. Extracellular space is greatly increased. This study thus indicates that the best incubation conditions are an oxygenated medium for 30-day-old chick telencephalic slices which are characterized by an aerobic metabolism, and a non-oxygenated medium for 1-day-old chick telencephalic slices which have a predominantly anaerobic metabolism.

Aerobiosis↗

Utilization of acetate by chick brain during postnatal maturation.

1. The study of the compartmentation of glutamate metabolism has been performed in the chick brain in vivo and in vitro in the presence of [U-14C]acetate between day 1 and day 30 of postnatal maturation. 2. The compartmentation of glutamate metabolism in vivo appears between day 1 and day 4 after hatching in the cerebral hemispheres and optic lobes. It is however more precocious in the optic lobes. In the cerebellum, it appears later, at about day 4 after hatching. The compartmentation of glutamate metabolism appears at the same time as the rapid incorporation of glucose into amino acids takes place in the cerebral hemispheres and the optic lobes. 3. In the chick telencephalon in vitro, the compartmentation of glutamate metabolism is visible from day 1 after hatching onwards. This difference is undoubtedly linked to the absence of an interference of glucose metabolism with acetate metabolism in vitro, and to the presence of a third compartment in the cerebral slices.

Acetates↗

Utilization of 3-hydroxybutyrate by chick cerebral hemispheres during postnatal maturation.

1. The utilization of 3-hydroxybutyrate has been studied in the chick telencephalon during its post-hatching maturation. 2. In the 1-day-old chick the blood concentration of 3-hydroxybutyrate appears to be relatively high and its value is 5 times that estimated in the 4- and 30-day-old chicks. 3. The determination of the cerebral arteriovenous differences of 3-hydroxybutyrate shows that the brain of the newly-hatched chick takes up 3 times more actively this ketone body than the brain of the 4-day-old bird does. 4. During incubation in a non-oxygenated and an oxygenated physiological medium, in the presence of 3-hydroxy [3-14C]butyrate, the specific radioactivity of the dicarboxylic amino acids in the 1-day-old chick brain slices is higher than in those of the 30-day-old chick, particularly in the oxygenated medium. 5. Thirty minutes after a subcutaneous injection of 3-hydroxy [3-14C]butyrate, the specific radioactivity of the dicarboxylic amino acids in the 1-day-old chick telencephalon is 3-4 times higher than that in the 4- and 30-day-old chick. 6. In conclusion, in the brain of the newly hatched chick, 3-hydroxybutyrate is an efficient precursor in the biosynthesis of dicarboxylic amino acids, particularly glutamate, and, as glucose, it is metabolically related to the "large compartment" of glutamate. 7. These results have been discussed comparatively to those previously obtained in the developing rodent brain.

3-Hydroxybutyric Acid↗

Glutaminase activity in the chick central nervous system during postnatal growth.

1. Glutaminase activity was evaluated in the chick cerebral hemispheres, optic lobes and cerebellum between the 1st and 30th day of postnatal growth. 2. Glutaminase activity is higher in the cerebral hemispheres than in the optic lobes and is lowest in the cerebellum. 3. It seems to be inversely related to the magnitude of the variations of glutamine concentration in the three areas. 4. No direct relation exists between enzyme activity and glutamate concentration in the three tissues.

Animals↗

Caffeine and the central nervous system: mechanisms of action, biochemical, metabolic and psychostimulant effects.

Caffeine is the most widely consumed central-nervous-system stimulant. Three main mechanisms of action of caffeine on the central nervous system have been described. Mobilization of intracellular calcium and inhibition of specific phosphodiesterases only occur at high non-physiological concentrations of caffeine. The only likely mechanism of action of the methylxanthine is the antagonism at the level of adenosine receptors. Caffeine increases energy metabolism throughout the brain but decreases at the same time cerebral blood flow, inducing a relative brain hypoperfusion. Caffeine activates noradrenaline neurons and seems to affect the local release of dopamine. Many of the alerting effects of caffeine may be related to the action of the methylxanthine on serotonin neurons. The methylxanthine induces dose-response increases in locomotor activity in animals. Its psychostimulant action on man is, however, often subtle and not very easy to detect. The effects of caffeine on learning, memory, performance and coordination are rather related to the methylxanthine action on arousal, vigilance and fatigue. Caffeine exerts obvious effects on anxiety and sleep which vary according to individual sensitivity to the methylxanthine. However, children in general do not appear more sensitive to methylxanthine effects than adults. The central nervous system does not seem to develop a great tolerance to the effects of caffeine although dependence and withdrawal symptoms are reported.

Animals↗

Potential teratogenic and neurodevelopmental consequences of coffee and caffeine exposure: a review on human and animal data.

The teratogenic effect of caffeine has been clearly demonstrated in rodents. The sensitivity of different animals species is variable. Malformations have been demonstrated in mice at 50-75 mg/kg of caffeine, whereas the lowest dose usually needed to induce malformations is 80 mg/kg in rats. However, when caffeine is administered in fractioned amounts during the day, 330 mg/kg/day are necessary to reach teratogenicity in rats. In rodents, the most frequently observed malformations are those of the limbs and digits, ectrodactyly, craniofacial malformations (labial and palatal clefts) and delays in ossification of limbs, jaw and sternum. Nevertheless, even in rodents, caffeine can be considered as a weak teratogenic agent, given the quite large quantities of caffeine necessary to induce malformations and the small number of animals affected. In humans, caffeine does not present any teratogenic risk. The increased risk of the most common congenital malformations entailed by moderate consumption of caffeine is very slight. However, caffeine potentiates the teratogenic effect of other substances, such as tobacco, alcohol, and acts synergistically with ergotamine and propranolol to induce materno-fetal vasoconstrictions leading to malformations induced by ischemia. Therefore, even though caffeine does not seem to be harmful to the human fetus when intake is moderate and spread out over the day, some associations, especially with alcohol, tobacco, and vasoconstrictive or anti-migraine medications should be avoided. Maternal consumption of caffeine affects brain composition, especially in case of a low-protein diet and also seems to interfere with zinc fixation in brain. Maternal exposure to caffeine induces also long-term consequences on sleep, locomotion, learning abilities, emotivity, and anxiety in rat offspring, whereas in humans, more studies are needed to ascertain long-term behavioral effects of caffeine ingestion by pregnant mothers.

Abortion, Spontaneous↗