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Stability of brain content of magnesium in experimental hypomagnesemia
Brain Research 769 Ž1997. 329–332
Research report
Stability of brain content of magnesium in experimental hypomagnesemia S. Poenaru a,b , R. Manicom a,b,) , S. Rouhani a,b , P. Aymard d , O. Bajenaru b , Y. Rayssiguier c , E. Emmanouillidis b , E. Gueux c , N. Nkanga b , J. Durlach b , J. Dall’ava a a SerÕice d’Explorations Fonctionnelles, Hopital Cochin, 27, rue du Fbg St-Jacques, 75014 Paris, France ˆ Laboratoire de Neuroendocrinologie, Faculte´ de Medecine des St-Peres, ´ ` 47, rue des St-Peres, ` 75006 Paris, France Laboratoire des Maladies metaboliques, Centre de recherches Zootechniques et Veterinaires de Theix, Clermont-Ferrand, France ´ ´´ d Laboratoire de Biochimie, Faculte´ de Pharmacie, Chatenay-Malabry, France b
c
Accepted 28 May 1997
Abstract Magnesium is important in cerebral function. If there is a deficiency and neurological symptoms accrue, we hypothesised that Mg 2q deficiency causes neurological symptoms by decreasing the level of Mg 2q in cerebral tissue. The content of magnesium was determined in 12 brain structures in magnesium-deficient rats. Experiments were carried out for 40 days in two groups of Wistar male rats made magnesium-deficient ŽMD. by a well-controlled diet Ž50 mg of Mg 2qrkg of food., and a control group ŽCG. rats fed normal diet Ž1 g of Mg 2qrkg of food.. At the end of the 40 days, the clinical signs of hypomagnesemia were sought in the MD rats and Mg 2q concentration levels were measured in the blood and brain. The results showed variable distribution of Mg 2q in the different brain structures, both in CG and MD rats; in the MD rats there is an important stability of global Mg 2q content of the brain. Although the global values for Mg 2q in the brain did not decline in MD rats, there was a significant decrease in Mg 2q in the brainstem. We conclude that the brain is able to maintain a stable concentration of Mg 2q during chronic hypomagnesemia, but its topographic variations could account for some of neurological signs accompanying this condition. q 1997 Elsevier Science B.V. Keywords: Magnesium-deficient rat; Brain structure; Magnesium brain content
1. Introduction
2. Materials and methods
Magnesium deficiency and its different neurologic manifestations in man has been extensively studied w2,3,10,11,8x and its clinical features Žtetany-attacks, convulsions, paraesthesias, muscular fasciculations, psycho-motoricity, instability, depression, sleep disorder, neurovegetative disorder, trophic disorder. and electrophysiologic features are well characterised. Magnesium deficiency has also been studied in animals, where it has many effects, indicating a role for magnesium in lipid metabolism and artherogenesis w6,12x. The clinical features of hypomagnesemia, both experimental and in man, suggest low magnesium levels may cause structural abnormalities of the central nervous system, and show how magnesium is important to neurons. We examined the effect of hypomagnesemia on the concentration of magnesium in different structures of the brain in rats.
2.1. Animals
)
Corresponding author, at address a. Fax: q33 Ž1. 4407-2538.
0006-8993r97r$17.00 q 1997 Elsevier Science B.V. All rights reserved. PII S 0 0 0 6 - 8 9 9 3 Ž 9 7 . 0 0 7 2 5 - 7
Experiments were carried out in 23 male Wistar rats Žweight 120–150 g.. The rats were placed in individual cages housed at the Laboratoire des Maladies Metabo´ liques du CRZV ŽCentre de Recherches Zootechniques et .. Veterinaires ´´ In each chamber the environment was controlled Ž218C, 60% humidity.. The lightrdark cycle was 12:12 h. The animals were randomly distributed into two groups to be studied for 40 days: the magnesium-deficient group ŽMDG. of 12 rats, and the control group ŽCG. of 11 rats. 2.2. Diet Both groups received the same, well controlled diet Žthe same quantity for CG as for the MDG.. The diet was designed to meet the recommendations of the American Institute of Nutrition w1x. The general formula for the
S. Poenaru et al.r Brain Research 769 (1997) 329–332
330
deficient magnesium diet was: 20% casein, 70.5% starch, 5% maize oil, 3.5% mineral mixture and 1% vitamin mixture. The magnesium content was 50 mgrkg of food in the magnesium-deficient group. The diet for the control group was supplemented with magnesium to a final concentration of 1 grkg of food. 2.3. Clinical surÕey The following measurements were made on the 20th and 40th days of the diet: weight, the presence of trophic lesions Žmild, moderate and severe loss of hairs, cataracts., and vasodilatation at the level of the ear-skin. 2.4. Blood examinations
Fig. 1. Magnesium concentrations in the plasma Ž20th and 40th days of the experiment.. Mean"S.D. Significant difference: ) ) P F 0.01, Student’s t-test.
On the 20th and 40th days, we obtained blood from the ether-anesthetized animals, in order to determine the plasma levels of calcium and magnesium, and the concentration of Mg 2q in the red cells using absorption spectrophotometry ŽPerkin-Elmer., as previously described w9x.
2.7. Statistical analysis
2.5. Isolation of cerebral structures On the 40th day, the animals were decapitated at the end of the dark phase of the day. Immediately after decapitation, rat brains were isolated, cooled and finely dissected using the technique of Glowinski and Iversen w4x, with our modifications ŽS.P. and S.R... We isolated 12 cerebral structures: the brainstem ŽBS., cerebellum ŽCB., hypothalamus ŽHT., thalamus ŽT., inferior and superior quadrigerminal colliculi ŽQC., olfactory bulbs ŽOB., tuberculi olfactorium ŽOTu., septum ŽS., hippocampus ŽHi., cortex piriformis ŽPIR., corpus striatum ŽCST. and the cortex ŽC.. 2.6. Tissue concentration of magnesium This was measured by absorption spectrophotometry ŽPerkin-Elmer. as described by MacIntyre and Davidsson w7x.
Difference in the magnesium concentration between groups were analysed using the Student t-test. Values are expressed as the mean " S.D. The results were considered significant if P F 0.05.
3. Results 3.1. Weight eÕolution The weight of the animals in CG at the end of the study was 279 " 22.7 g and in the MDG 247 " 29.1 g Ž P F 0.01.. 3.2. Clinical signs of hypomagnesemia There were no hypomagnesemic lesions in CG, while in the MDG we noticed cataracts in 2 rats Ž8.33%., severe loss of hairs in 5 rats Ž20.38%., moderate loss of hairs in 8 rats Ž33.33%. and mild loss of hairs in 9 rats Ž37.5%.. The ear-skin vasodilatation was present in more than 70% in the MDG group, while being absent in the CG.
Table 1 Brain tissue Mg 2q concentrations Žmgrg fresh tissue. Žmean " S.D., Student’s t-test. Structures
Control group
Mg 2q-Deficient group
Statistical significance
1. Brainstem 2. Cerebellum 3. Hypothalamus 4. Thalamus 5. Quadrigerminal colliculi 6. Olfactory bulbs 7. Olfactory tubercules 8. Septum 9. Hippocampus 10. Cortex piriformis 11. Corpus striatum 12. Cortex
148.27 " 23.1 144.54 " 10.9 145.81 " 15.1 160.77 " 21.4 142.70 " 19.4 139.60 " 13.7 160.63 " 25.2 133.00 " 24 151.50 " 20.5 151.10 " 20.5 168.81 " 21.8 141.45 " 18.1
130.00 " 14,3 137.91 " 12.1 143.58 " 13.8 144.88 " 21.2 164.40 " 16 145.25 " 28.4 153.83 " 24.2 121.00 " 35.4 153.25 " 14.2 144.77 " 22.8 150.63 " 26.5 127.60 " 22.7
P F 0.05 Non-significant Non-significant Non-significant P F 0.01 Non-significant Non-significant Non-significant Non-significant Non-significant Non-significant Non-significant
S. Poenaru et al.r Brain Research 769 (1997) 329–332
331
3.3. Blood sample determination On the 20th day we noticed an significant decrease of the plasma levels of magnesium in the MDG Ž0.17 " 0.03 mMrl vs. 0.89 " 0.06 mMrl in the CG.. The decrease was more pronounced on the 40th day: 0.13 " 0.01 mMrl in the MDG vs. 0.84 " 0.05 mMrl in the CG Ž P F 0.01. ŽFig. 1.. We also noticed an significant decrease of the Mg 2q concentration in the red cells in the MDG Ž1.78 " 0.1 mMrl vs. 3.26 " mMrl in the CG Ž P F 0.01... On the 40th day this difference was maintained Ž1.99 " 0.3 mMrl and 3.21 " 0.1 mMrl, respectively. ŽFig. 3.. On the 20th hypercalcemia was noted Žcalcium concentration 2.88 " 0.1 mMrl. in the MDG, versus 2.64 " 0.1 mMrl in the CG Ž P F 0.01.. On the 40th day, serum calcium had declined somewhat by Ž2.64 " 0,1 mMrl in MSG., but was still greater than in the CG Ž2.46 " 0.1 mMrl. Ž P F 0.05. ŽFig. 2.. 3.4. Brain tissue Mg 2 q concentrations (Table 1) In the CG the brain tissue Mg 2q concentration in fresh tissue, ranges between 133 " 24 mgrg and 168.81 " 21.8 mgrg in the MDG, the tissue Mg 2q concentration ranges between 121 " 35.4 mgrg and 164.10 " 16 mgrg. The topographic distribution of Mg 2q concentration in different brain structures was not uniform: In CG: the highest concentration was in: tuberculi olfactorium, corpus striatum and thalamus; the lowest concentration was in: cerebellum, hypothalamus, inferior and superior quadrigerminal colliculi, olfactory bulbs, septum and cortex.
Fig. 3. Magnesium concentration in the red cells Ž20th and 40th days of the experiment.. Mean"S.D. Significant difference: ) ) P F 0.01, Student’s t-test.
In MDG: the highest concentration was in inferior and superior quadrigerminal colliculi; the lowest concentration was in septum and cortex. We also noticed A tendency to a decrease of the Mg 2q concentration in the MDG vs. CG in 9 structures Žfrom 12., but this achieved statistical significance only in the brainstem Ž P F 0.05.; in the other three structures of the MDG, the Mg 2q concentration increased but this fact is significant only for the inferior and superior quadrigerminal colliculi Ž P F 0.01..
4. Discussion
Fig. 2. Calcium concentrations in the plasma Ž20th and 40th days of the experiment.. Mean"S.D. Significant difference: ) P F 0.05, ) ) P F 0.01, Student’s t-test.
The ocular and cutaneous abnormalities we noted in the magnesium-deficient group are in accordance with those reported by other authors w5,13x. In spite of a well-standardized diet, which was closely surveyed, the levels of the plasmatic and red cells Mg 2q, as well as of the plasmatic Ca2q in the control group, had some variations during the study, but these were not significant. Variations were consistent with usually reported in this model w5,13x. Also, the extreme concentrations of whole brain tissue Mg 2q are close to the average values reported by MacIntyre and Davidsson w7x but, while in the CG, the topographic variations among different brain structures reach 27%, in the magnesium deficit group these topographic variations reach 35%, the greatest variations between the two groups being in inferior and superior quadrigerminal colliculi Žgreatest in the MDG vs. CG. and
332
S. Poenaru et al.r Brain Research 769 (1997) 329–332
the brainstem Žlowest in the MDG vs. CG., both having statistical significance. Thus, the brain tissue concentration of Mg 2q has smaller variations in the hypomagnesemic rat than the plasma and red cells Ž‘circulating’. Mg 2q concentration. In fact, only two cerebral structures had significant changes of the Mg 2q concentration during hypomagnesemia: the brainstem Ždiminution. and the quadrigerminal colliculi Ženhancement.. In the other brain structures there was a tendency to decrease in the septum, cortex, thalamus and corpus striatum. There was no effect of dietary and plasma Mg 2q deficiency on tissue Mg 2q concentration in the hypothalamus, hippocampus, olfactory bulbs, cerebellum, cortex piriformis and tuberculi olfactorium. The relative stability of the brain tissue Mg 2q concentration, in these conditions, could be related to homeostatic mechanisms in the brain which protect the tissue magnesium content. In spite of variations in circulating Mg 2q concentration, Mg 2q is indispensable to the neuronal metabolism w7x. In support of this we can see that in the CG the average global concentration of brain tissue Mg 2q is twice that in the red cells, while in the magnesium deficit group it is 3-times greater than that in the red cells. At the same time, the topographic variations of brain tissue Mg 2q concentration have a significant decrease in a fundamental functional structure Žthe brainstem., which could be an important aspect in the explanation of some of the neurologic manifestations of hypomagnesemia, especially the sleep disorders. The significance of the increase of the Mg 2q concentration in the quadrigerminal colliculi remains unclear. In conclusion: Ž1. brain tissue Mg 2q concentration varies from one structure to another, both in normal and magnesium-deficient rat; Ž2. in hypomagnesemia caused by dietary restriction of Mg 2q conditions, there is a significant decrease of the Mg 2q concentration in the brainstem, a structure essential for autonomic functions, the control of muscle tone and the vigilance states; Ž3. global brain tissue Mg 2q homeostasis is maintained in the magnesium-deficient rat; Ž4. The brain’s capacity to maintain a certain
stability of its Mg 2q content makes less probable its direct implication in the pathogenesis of the neurological and psychiatric troubles accompanying hypomagnesemia; these clinical consequences could be perhaps better related to the complex functions of different neuronal receptors, in which Mg 2q has some regulatory implications.
References w1x American Institute of Nutrition ŽAIN., Report of the American Institute of Nutrition ad hoc committee on standards for nutrition studies, J. Nutr. 107 Ž1977. 1340–1348. w2x J. Durlach, Aspects cliniques du deficit magnesique chronique, Vie ´ ´ Medicale au Canada Franc¸ais 2 Ž1977. 146–180. ´ w3x J. Durlach, Magnesium in clinical practice, John Libbey, London, 1988. w4x J. Glowinski, L. Iversen, Regional studies of catecholamine in rat brain and the dispositive of w 3 HxDopamine and w 3 HxDopa in various regions of the brain, J. Neurochem. 13 Ž1966. 665–669. w5x E. Gueux, Les modifications du metabolisme lipidique et leurs ´ implications pathologiques au cours du deficit magnesique, These, ´ ´ ` Clermont-Ferrand, 1980. w6x S.L. Kraeuter, R. Schwartz, Blood and mast histamine levels in magnesium deficient rats, J. Nutr. 110 Ž1980. 851–858. w7x J. Mac Intyre, D. Davidsson, The production of secondary potassium depletion, sodium retention nephrocalcinosis and hypercalcaemia by magnesium deficiency, Biochem. J. 70 Ž1958. 456–459. w8x T. Maekawa, T. Tsutsuri, T. Somo, T. Suzuky, F. Takeshita, Serum concentration of magnesium in stroke patients Cardiovascular disease II, Magnesium Bull. 2 Ž1989. 45. w9x Perkin-Elmer, ‘Cook Book’, Analysis of Serum Determination of Ca, Mg, Na, K. Page ref BCI, R. Perkin-Elmer Corp., Norwalk, CT, 1973. w10x S. Poenaru, J. Durlach, D. Auphelle, Analyse electro-clinique du ´ sommeil de 100 cas de tetanie par deficit magnesique, Magnesium ´ ´ ´ Bull. 1 Ž1981. 24. w11x S. Poenaru, J. Durlach, S. Rouhani, A. Reba, D. Auphelle, M. Iovino, Analyse electro-clinique du sommeil de 100 cas de tetanie ´ ´ par deficit magnesique, Magnesium Bull. 1 Ž1983. 19–23. ´ ´ w12x Y. Rayssiguier, E. Gueux, D. Weiser, Effect of magnesium deficiency on lipid metabolism in rats fed a high carbohydrate diet, J. Nutr. 11 Ž1981. 1876–1883. w13x S. Rouhani, Etude electrophysiologique de l’hypomagnesemie ´ ´´ experimentale non traitee ´ ´ et traitee ´ par un complexe magnesien, ´ These 1982. ` pour le Doctorat en Medecine, ´
Research report
Stability of brain content of magnesium in experimental hypomagnesemia S. Poenaru a,b , R. Manicom a,b,) , S. Rouhani a,b , P. Aymard d , O. Bajenaru b , Y. Rayssiguier c , E. Emmanouillidis b , E. Gueux c , N. Nkanga b , J. Durlach b , J. Dall’ava a a SerÕice d’Explorations Fonctionnelles, Hopital Cochin, 27, rue du Fbg St-Jacques, 75014 Paris, France ˆ Laboratoire de Neuroendocrinologie, Faculte´ de Medecine des St-Peres, ´ ` 47, rue des St-Peres, ` 75006 Paris, France Laboratoire des Maladies metaboliques, Centre de recherches Zootechniques et Veterinaires de Theix, Clermont-Ferrand, France ´ ´´ d Laboratoire de Biochimie, Faculte´ de Pharmacie, Chatenay-Malabry, France b
c
Accepted 28 May 1997
Abstract Magnesium is important in cerebral function. If there is a deficiency and neurological symptoms accrue, we hypothesised that Mg 2q deficiency causes neurological symptoms by decreasing the level of Mg 2q in cerebral tissue. The content of magnesium was determined in 12 brain structures in magnesium-deficient rats. Experiments were carried out for 40 days in two groups of Wistar male rats made magnesium-deficient ŽMD. by a well-controlled diet Ž50 mg of Mg 2qrkg of food., and a control group ŽCG. rats fed normal diet Ž1 g of Mg 2qrkg of food.. At the end of the 40 days, the clinical signs of hypomagnesemia were sought in the MD rats and Mg 2q concentration levels were measured in the blood and brain. The results showed variable distribution of Mg 2q in the different brain structures, both in CG and MD rats; in the MD rats there is an important stability of global Mg 2q content of the brain. Although the global values for Mg 2q in the brain did not decline in MD rats, there was a significant decrease in Mg 2q in the brainstem. We conclude that the brain is able to maintain a stable concentration of Mg 2q during chronic hypomagnesemia, but its topographic variations could account for some of neurological signs accompanying this condition. q 1997 Elsevier Science B.V. Keywords: Magnesium-deficient rat; Brain structure; Magnesium brain content
1. Introduction
2. Materials and methods
Magnesium deficiency and its different neurologic manifestations in man has been extensively studied w2,3,10,11,8x and its clinical features Žtetany-attacks, convulsions, paraesthesias, muscular fasciculations, psycho-motoricity, instability, depression, sleep disorder, neurovegetative disorder, trophic disorder. and electrophysiologic features are well characterised. Magnesium deficiency has also been studied in animals, where it has many effects, indicating a role for magnesium in lipid metabolism and artherogenesis w6,12x. The clinical features of hypomagnesemia, both experimental and in man, suggest low magnesium levels may cause structural abnormalities of the central nervous system, and show how magnesium is important to neurons. We examined the effect of hypomagnesemia on the concentration of magnesium in different structures of the brain in rats.
2.1. Animals
)
Corresponding author, at address a. Fax: q33 Ž1. 4407-2538.
0006-8993r97r$17.00 q 1997 Elsevier Science B.V. All rights reserved. PII S 0 0 0 6 - 8 9 9 3 Ž 9 7 . 0 0 7 2 5 - 7
Experiments were carried out in 23 male Wistar rats Žweight 120–150 g.. The rats were placed in individual cages housed at the Laboratoire des Maladies Metabo´ liques du CRZV ŽCentre de Recherches Zootechniques et .. Veterinaires ´´ In each chamber the environment was controlled Ž218C, 60% humidity.. The lightrdark cycle was 12:12 h. The animals were randomly distributed into two groups to be studied for 40 days: the magnesium-deficient group ŽMDG. of 12 rats, and the control group ŽCG. of 11 rats. 2.2. Diet Both groups received the same, well controlled diet Žthe same quantity for CG as for the MDG.. The diet was designed to meet the recommendations of the American Institute of Nutrition w1x. The general formula for the
S. Poenaru et al.r Brain Research 769 (1997) 329–332
330
deficient magnesium diet was: 20% casein, 70.5% starch, 5% maize oil, 3.5% mineral mixture and 1% vitamin mixture. The magnesium content was 50 mgrkg of food in the magnesium-deficient group. The diet for the control group was supplemented with magnesium to a final concentration of 1 grkg of food. 2.3. Clinical surÕey The following measurements were made on the 20th and 40th days of the diet: weight, the presence of trophic lesions Žmild, moderate and severe loss of hairs, cataracts., and vasodilatation at the level of the ear-skin. 2.4. Blood examinations
Fig. 1. Magnesium concentrations in the plasma Ž20th and 40th days of the experiment.. Mean"S.D. Significant difference: ) ) P F 0.01, Student’s t-test.
On the 20th and 40th days, we obtained blood from the ether-anesthetized animals, in order to determine the plasma levels of calcium and magnesium, and the concentration of Mg 2q in the red cells using absorption spectrophotometry ŽPerkin-Elmer., as previously described w9x.
2.7. Statistical analysis
2.5. Isolation of cerebral structures On the 40th day, the animals were decapitated at the end of the dark phase of the day. Immediately after decapitation, rat brains were isolated, cooled and finely dissected using the technique of Glowinski and Iversen w4x, with our modifications ŽS.P. and S.R... We isolated 12 cerebral structures: the brainstem ŽBS., cerebellum ŽCB., hypothalamus ŽHT., thalamus ŽT., inferior and superior quadrigerminal colliculi ŽQC., olfactory bulbs ŽOB., tuberculi olfactorium ŽOTu., septum ŽS., hippocampus ŽHi., cortex piriformis ŽPIR., corpus striatum ŽCST. and the cortex ŽC.. 2.6. Tissue concentration of magnesium This was measured by absorption spectrophotometry ŽPerkin-Elmer. as described by MacIntyre and Davidsson w7x.
Difference in the magnesium concentration between groups were analysed using the Student t-test. Values are expressed as the mean " S.D. The results were considered significant if P F 0.05.
3. Results 3.1. Weight eÕolution The weight of the animals in CG at the end of the study was 279 " 22.7 g and in the MDG 247 " 29.1 g Ž P F 0.01.. 3.2. Clinical signs of hypomagnesemia There were no hypomagnesemic lesions in CG, while in the MDG we noticed cataracts in 2 rats Ž8.33%., severe loss of hairs in 5 rats Ž20.38%., moderate loss of hairs in 8 rats Ž33.33%. and mild loss of hairs in 9 rats Ž37.5%.. The ear-skin vasodilatation was present in more than 70% in the MDG group, while being absent in the CG.
Table 1 Brain tissue Mg 2q concentrations Žmgrg fresh tissue. Žmean " S.D., Student’s t-test. Structures
Control group
Mg 2q-Deficient group
Statistical significance
1. Brainstem 2. Cerebellum 3. Hypothalamus 4. Thalamus 5. Quadrigerminal colliculi 6. Olfactory bulbs 7. Olfactory tubercules 8. Septum 9. Hippocampus 10. Cortex piriformis 11. Corpus striatum 12. Cortex
148.27 " 23.1 144.54 " 10.9 145.81 " 15.1 160.77 " 21.4 142.70 " 19.4 139.60 " 13.7 160.63 " 25.2 133.00 " 24 151.50 " 20.5 151.10 " 20.5 168.81 " 21.8 141.45 " 18.1
130.00 " 14,3 137.91 " 12.1 143.58 " 13.8 144.88 " 21.2 164.40 " 16 145.25 " 28.4 153.83 " 24.2 121.00 " 35.4 153.25 " 14.2 144.77 " 22.8 150.63 " 26.5 127.60 " 22.7
P F 0.05 Non-significant Non-significant Non-significant P F 0.01 Non-significant Non-significant Non-significant Non-significant Non-significant Non-significant Non-significant
S. Poenaru et al.r Brain Research 769 (1997) 329–332
331
3.3. Blood sample determination On the 20th day we noticed an significant decrease of the plasma levels of magnesium in the MDG Ž0.17 " 0.03 mMrl vs. 0.89 " 0.06 mMrl in the CG.. The decrease was more pronounced on the 40th day: 0.13 " 0.01 mMrl in the MDG vs. 0.84 " 0.05 mMrl in the CG Ž P F 0.01. ŽFig. 1.. We also noticed an significant decrease of the Mg 2q concentration in the red cells in the MDG Ž1.78 " 0.1 mMrl vs. 3.26 " mMrl in the CG Ž P F 0.01... On the 40th day this difference was maintained Ž1.99 " 0.3 mMrl and 3.21 " 0.1 mMrl, respectively. ŽFig. 3.. On the 20th hypercalcemia was noted Žcalcium concentration 2.88 " 0.1 mMrl. in the MDG, versus 2.64 " 0.1 mMrl in the CG Ž P F 0.01.. On the 40th day, serum calcium had declined somewhat by Ž2.64 " 0,1 mMrl in MSG., but was still greater than in the CG Ž2.46 " 0.1 mMrl. Ž P F 0.05. ŽFig. 2.. 3.4. Brain tissue Mg 2 q concentrations (Table 1) In the CG the brain tissue Mg 2q concentration in fresh tissue, ranges between 133 " 24 mgrg and 168.81 " 21.8 mgrg in the MDG, the tissue Mg 2q concentration ranges between 121 " 35.4 mgrg and 164.10 " 16 mgrg. The topographic distribution of Mg 2q concentration in different brain structures was not uniform: In CG: the highest concentration was in: tuberculi olfactorium, corpus striatum and thalamus; the lowest concentration was in: cerebellum, hypothalamus, inferior and superior quadrigerminal colliculi, olfactory bulbs, septum and cortex.
Fig. 3. Magnesium concentration in the red cells Ž20th and 40th days of the experiment.. Mean"S.D. Significant difference: ) ) P F 0.01, Student’s t-test.
In MDG: the highest concentration was in inferior and superior quadrigerminal colliculi; the lowest concentration was in septum and cortex. We also noticed A tendency to a decrease of the Mg 2q concentration in the MDG vs. CG in 9 structures Žfrom 12., but this achieved statistical significance only in the brainstem Ž P F 0.05.; in the other three structures of the MDG, the Mg 2q concentration increased but this fact is significant only for the inferior and superior quadrigerminal colliculi Ž P F 0.01..
4. Discussion
Fig. 2. Calcium concentrations in the plasma Ž20th and 40th days of the experiment.. Mean"S.D. Significant difference: ) P F 0.05, ) ) P F 0.01, Student’s t-test.
The ocular and cutaneous abnormalities we noted in the magnesium-deficient group are in accordance with those reported by other authors w5,13x. In spite of a well-standardized diet, which was closely surveyed, the levels of the plasmatic and red cells Mg 2q, as well as of the plasmatic Ca2q in the control group, had some variations during the study, but these were not significant. Variations were consistent with usually reported in this model w5,13x. Also, the extreme concentrations of whole brain tissue Mg 2q are close to the average values reported by MacIntyre and Davidsson w7x but, while in the CG, the topographic variations among different brain structures reach 27%, in the magnesium deficit group these topographic variations reach 35%, the greatest variations between the two groups being in inferior and superior quadrigerminal colliculi Žgreatest in the MDG vs. CG. and
332
S. Poenaru et al.r Brain Research 769 (1997) 329–332
the brainstem Žlowest in the MDG vs. CG., both having statistical significance. Thus, the brain tissue concentration of Mg 2q has smaller variations in the hypomagnesemic rat than the plasma and red cells Ž‘circulating’. Mg 2q concentration. In fact, only two cerebral structures had significant changes of the Mg 2q concentration during hypomagnesemia: the brainstem Ždiminution. and the quadrigerminal colliculi Ženhancement.. In the other brain structures there was a tendency to decrease in the septum, cortex, thalamus and corpus striatum. There was no effect of dietary and plasma Mg 2q deficiency on tissue Mg 2q concentration in the hypothalamus, hippocampus, olfactory bulbs, cerebellum, cortex piriformis and tuberculi olfactorium. The relative stability of the brain tissue Mg 2q concentration, in these conditions, could be related to homeostatic mechanisms in the brain which protect the tissue magnesium content. In spite of variations in circulating Mg 2q concentration, Mg 2q is indispensable to the neuronal metabolism w7x. In support of this we can see that in the CG the average global concentration of brain tissue Mg 2q is twice that in the red cells, while in the magnesium deficit group it is 3-times greater than that in the red cells. At the same time, the topographic variations of brain tissue Mg 2q concentration have a significant decrease in a fundamental functional structure Žthe brainstem., which could be an important aspect in the explanation of some of the neurologic manifestations of hypomagnesemia, especially the sleep disorders. The significance of the increase of the Mg 2q concentration in the quadrigerminal colliculi remains unclear. In conclusion: Ž1. brain tissue Mg 2q concentration varies from one structure to another, both in normal and magnesium-deficient rat; Ž2. in hypomagnesemia caused by dietary restriction of Mg 2q conditions, there is a significant decrease of the Mg 2q concentration in the brainstem, a structure essential for autonomic functions, the control of muscle tone and the vigilance states; Ž3. global brain tissue Mg 2q homeostasis is maintained in the magnesium-deficient rat; Ž4. The brain’s capacity to maintain a certain
stability of its Mg 2q content makes less probable its direct implication in the pathogenesis of the neurological and psychiatric troubles accompanying hypomagnesemia; these clinical consequences could be perhaps better related to the complex functions of different neuronal receptors, in which Mg 2q has some regulatory implications.
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