Astrocytes and myelination

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Astrocytes and myelination

Postby bromley » Thu Mar 16, 2006 3:06 am

Looks like a good finding.

Thursday is turning out to be a good day so far (in terms of MS news stories).

Ian

New 'stars' in formation of nerve cell insulation 16 March 2006
The insulating myelin sheath enwrapping the cable-like axons of nerve cells is the major target of attack of the immune system in multiple sclerosis. Such attack causes neural short-circuits that give rise to the muscle weakness, loss of coordination, and speech and visual loss in the disease.

Now, Douglas Fields of the National Institute of Child Health and Human Development and his colleagues have reported in the March 16, 2006, issue of Neuron that supporting cells called astrocytes in the central nervous system (CNS) promote myelination by releasing an immune system molecule that triggers myelin-forming cells to action. The finding, they say, "may offer new approaches to treating demyelinating diseases."

Astrocytes, so named because of their star-like shape, are the most prominent supporting cells in the nervous system. They provide critical regulatory molecules that enable nerve cells to develop and connect properly.

In their studies, Fields and his colleagues sought to understand other research findings indicating that the electrical activity of nerve cells somehow triggers myelin-producing cells, called oligodendrocytes, to form the myelin membrane surrounding the nerve cells.

In their studies, the researchers cultured rat and mice neurons together with oligodendrocytes and conducted experiments to understand the mechanism of myelin formation. They found that electrical stimulation of the neurons caused production of the energy molecule ATP, and this ATP increases myelination.

Drawing on other researchers' findings that an immune signaling molecule called leukemia inhibitory factor (LIF) might be involved, they explored whether LIF was a key molecule in the ATP-triggered myelination machinery. Their experiments revealed LIF's central role in the machinery, and further studies showed that astrocytes were the source of that LIF.

Indeed, when they tested directly whether astrocytes were important in promoting myelination in the cell cultures, they found the cells to be potent promoters of the process.

"Taken together, these results reveal a new mechanism by which electrical activity promotes myelination of CNS axons at a later developmental stage and possibly into postnatal life," concluded the researcher. They wrote that the "new findings may provide novel approaches to understanding and treating myelin disorders in the CNS" after the immature oligodendrocytes have matured into myelinating cells.

The researchers include Tomoko Ishibashi, Kelly A. Dakin, Beth Stevens, Philip R. Lee, and R. Douglas Fields of the National Institute of Child Health and Human Development in Bethesda, MD; Serguei V. Kozlov and Colin L. Stewart of the National Cancer Institute in Bethesda, MD. This work was supported by the intramural research program at National Institutes of Health, National Institute of Child Health and Human Development.

Ishibashi et al.: "Astrocytes Promote Myelination in Response to Electrical Impulses." Publishing in Neuron 49, 823–832, March 16, 2006. DOI 10.1016/j.neuron.2006.02.006

www.neuron.org

Source: Cell Press
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Postby Dunmann » Thu Mar 16, 2006 7:13 am

Nice find Bromley.

I find it interesting that ATP was mentioned in this article.
They found that electrical stimulation of the neurons caused production of the energy molecule ATP, and this ATP increases myelination.

I wonder if, or how this ATP relates to the ATP that you can you can easily increase by taking Creatine, a well known and widely used fitness supplement? Wikipedia has a thorough definition of Creatine.
http://en.wikipedia.org/wiki/Creatine
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Postby bernie100 » Thu Mar 16, 2006 11:22 am

Hi all

I looked at the site giving information on creatine but now can't always understand what I am reading, so could you explain in more simple terms what creatine has to do with ATP

Thanks in advance
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Postby Dunmann » Thu Mar 16, 2006 12:37 pm

Sorry if I didn't explain this well before. I'm just hypothesizing here, and there may be no correlation between the ATP mentioned in the article and the ATP generated by Creatine.

Here's some more info on Creatine.

"As we discussed in this creatine information article, ATP is the main fuel for your muscle contractions, and this is achieved by the ATP releasing a phosphate and becoming an ADP. With extra creatine in your muscles, you regenerate ATP through the creatine release its phosphate which combines with the ADP to form ATP.
This ATP regeneration keeps your body from relying on glycolysis, which is process where lactic acid is built up during your workout. The benefit of this is clear: the reduced lactic acid allows you to workout longer and harder, thus maximizing every muscle's workout, and allows you to gain more muscle, strength and size. Another benefit of creatine supplements is you won't feel tired as easily during workouts."

More info.

http://www.bodybuildingforyou.com/creat ... ydrate.htm
http://www.bodybuildingforyou.com/creat ... nefits.htm
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Re: Astrocytes and myelination (and creatine)

Postby NHE » Fri Mar 17, 2006 4:00 am

Note that I'm not promoting the use of creatine, only providing more information for those who might be interested in it.

This information is from Healthnotes.com (see note at end)

Creatine Monohydrate

What is it?
Creatine (creatine monohydrate) is a colorless, crystalline substance used in muscle tissue for the production of phosphocreatine, an important factor in the formation of adenosine triphosphate (ATP), the source of energy for muscle contraction and many other functions in the body.(1, 2)

Creatine monohydrate supplementation increases phosphocreatine levels in muscle in most people, especially when accompanied by exercise or carbohydrate intake.(3, 4) However, about 30% of people who take creatine supplements fail to retain significant quantities in the muscle,(5, 6) which may explain the inconsistent results reported in studies of the effects of creatine on athletic performance.

Creatine may increase exercise-related gains in lean body mass,(7, 8, 9) though how much of these gains represents more muscle and how much is simply water retention is unclear.(10) Most, though not all, controlled studies have shown that 20 grams per day of creatine monohydrate taken for five to six days by sedentary or moderately active people, improves performance and delays muscle fatigue during short-duration, high-intensity exercise such as sprinting or weight lifting.(11, 12, 13) However, elderly people appear to gain only minimal, if any, exercise performance benefits from creatine supplementation,(14, 15) and performance outcomes for trained athletes using creatine supplements in competitive situations have not been consistent.(16, 17, 18) Creatine supplementation does not appear to increase endurance performance and may impair it by contributing to weight gain.(19)

Very little research has been done to investigate the exercise performance effects of long-term (over one month) creatine supplementation. Two controlled long-term trials using untrained women(20) or trained men(21) found that creatine improved gains made in strength and lean body mass from weight-training programs. However, a third preliminary trial found only insignificant gains from creatine supplementation in weight-training football players.(22)


The amount of creatine within cells may be deficient in people with muscular dystrophy. This deficiency may contribute to the weakness and degeneration of muscle tissue seen in this condition. A case report described a 9-year old boy with muscular dystrophy who experienced improved muscle performance after creatine supplementation.(23) A double-blind trial found that creatine supplementation (10 grams per day for adults, 5 grams per day for children) slightly but significantly improved muscle strength and performance of daily activities in people with varying types of muscular dystrophy.(24) Creatine supplementation has also been reported to improve strength in certain rare diseases of muscle and energy metabolism.(25, 26, 27)

For people with congestive heart failure, intravenous creatine has been found to improve heart function, but oral supplementation has not been effective, though skeletal muscle function does improve.(28, 29)

A double-blind, study found that 20 grams per day of creatine taken for five days followed by 10 grams per day for 51 days significantly lowered serum total cholesterol and triglycerides, but did not change either LDL or HDL cholesterol, in both men and women.(30) However, another double-blind trial found no change in any of these blood levels in trained athletes using creatine during a 12-week strength training program.(31) Creatine supplementation in this negative trial was lower—only 5 grams per day was taken for the last 11 weeks of the study.

Where is it found?
Creatine is produced naturally in the human liver, pancreas, and kidneys. It is concentrated primarily in muscle tissues, including the heart. Animal proteins, including fish, are the main source of the 1–2 grams per day of dietary creatine most people consume. Supplements in the form of creatine monohydrate are well absorbed and tolerated by the stomach.

Creatine monohydrate has been used in connection with the following conditions (refer to the individual health concern for complete information):

Rating/Health Concerns
*** - Athletic performance (for high-intensity, short duration exercise or sports with alternating low- and high-intensity efforts)

** - Athletic performance (for non-weight bearing endurance exercise)

* - Congestive heart failure, High cholesterol, High triglycerides, Muscular dystrophy

    Key
    *** Reliable and relatively consistent scientific data showing a substantial health benefit.
    ** Contradictory, insufficient, or preliminary studies suggesting a health benefit or minimal health benefit.
    * For an herb, supported by traditional use but minimal or no scientific evidence. For a supplement, little scientific support and/or minimal health benefit.

Who is likely to be deficient?
People involved in intense physical activity, especially those limiting their intake of red meat, may have low muscle stores of creatine. Several muscle diseases, as well as rheumatoid arthritis, and chronic circulatory and respiratory diseases, are associated with lowered creatine levels.(32)

How much is usually taken?
Two methods are used for supplementing with creatine. In the loading method, 20 grams of creatine per day (in four divided amounts mixed well in warm liquid) are taken for five to six days.(33) Muscle creatine levels increase rapidly, which is beneficial if a short-term rise in force is needed, such as during a weight-lifting competition, football game, or sprinting. To maintain muscle creatine levels after this loading period, 2–10 grams per day may be effective.(34, 35)

In another method, 3 grams of creatine monohydrate per day are taken over an extended training period of at least four weeks, during which muscle creatine levels rise more slowly, eventually reaching levels similar to those achieved with the loading method.(36) However, no trials testing exercise performance changes have been done using this method. Taking creatine with sugar appears to maximize muscle uptake.(37, 38)

Caffeine intake should not be excessive, as large amounts may counteract the benefits of creatine supplementation.(39)

Are there any side effects or interactions?
Little is known about long-term side effects of creatine, but no consistent toxicity has been reported in studies of creatine supplementation. In a study of side effects of creatine, diarrhea was the most commonly reported adverse effect of creatine supplementation, followed by muscle cramping.(40) Some reports showed that kidney, liver, and blood functions were not affected by short-term higher amounts (41, 42) or long-term lower amounts (43, 44) of creatine supplementation in healthy young adults. In a small study of people taking 5–30 grams per day, no change in kidney function appeared after up to five years of supplementation.(45) However, interstitial nephritis, a serious kidney condition, developed in an otherwise healthy young man, supplementing with 20 grams of creatine per day.(46) Improvement in kidney function followed avoidance of creatine. Details of this case strongly suggest that creatine supplementation triggered this case of kidney disease. Creatine supplementation may also be dangerous for people with existing kidney disease. In one report, a patient with nephrotic syndrome (a kidney disorder) developed glomerulosclerosis (another serious kidney condition) while taking creatine. when the creatine was discontinued, the glomerulosclerosis resolved.(47)

Muscle cramping after creatine supplementation has been anecdotally reported in three studies.(48, 49, 50)

At the time of writing, there were no well-known drug interactions with creatine monohydrate.

References
1. Greenhaff PL, Bodin K, Soderlund K, et al. Effect of oral creatine supplementation on skeletal muscle phosphocreatine resynthesis. Am J Physiol 1994;266:E725-30.

2. Greenhaff PL. Creatine and its application as an ergogenic aid. Int J Sport Nutr 1995;5:94-101.

3. Harris RC, Soderlund K, Hultman E. Elevation of creatine in resting and exercised muscle of normal subjects by creatine supplementation. Clin Sci 1992;83:367-74.

4. Green AL, Simpson EJ, Littlewood JJ, et al. Carbohydrate ingestion augments creatine retention during creatine feeding in humans. Acta Physiol Scand 1996;158:195-202.

5. Greenhaff PL, Bodin K, Soderlund K, et al. Effect of oral creatine supplementation on skeletal muscle phosphocreatine resynthesis. Am J Physiol 1994;266:E725-30.

6. Casey A, Constantin-Teodosiu D, Howell S, et al. Creatine supplementation favorably affects performance and muscle metabolism during maximal intensity exercise in humans. Am J Physiol 1996;271:E31-E7.

7. Stone MH, Sanborn K, Smith LL, et al. Effects of in-season (5-weeks) creatine and pyruvate supplementation on anaerobic performance and body composition in American football players. Int J Sport Nutr 1999;9:146-65.

8. Earnest CP, Snell PG, Rodriguez R, et al. The effect of creatine monohydrate ingestion on anaerobic power indices, muscular strength and body composition. Acta Physiol Scand 1995;153:207-9.

9. Stout JR, Eckerson J, Noonan D, et al. The effects of a supplement designed to augment creatine uptake on exercise performance and fat-free mass in football players. Med Sci Sports Exerc 1997;29:S251.

10. Kreider RB, Ferreira M, Wilson M, et al. Effects of creatine supplementation on body composition, strength, and sprint performance. Med Sci Sports Exerc 1998;30:73-82.

11. Toler SM. Creatine is an ergogen for anaerobic exercise. Nutr Rev 1997;55:21-5 [review].

12. Greenhaff PL. The nutritional biochemistry of creatine. J Nutr Biochem 1997;8:610-8 [review].

13. Greenhaff PL, Casey A, Short AH, et al. Influence of oral creatine supplementation on muscle torque during repeated bouts of maximal voluntary exercise in man. Clin Sci 1993;84:565-71.

14. Tarnopolsky MA. Potential benefits of creatine monohydrate supplementation in the elderly. Curr Opin Clin Nutr Metab Care 2000;3:497-502 [review].

15. Rawson ES, Clarkson PM. Acute creatine supplementation in older men. Int J Sports Med 2000;21:71-5.

16. Mujika I, Padilla S. Creatine supplementation as an ergogenic aid for sports performance in highly trained athletes: a critical review. Int J Sports Med 1997;18:491-6.

17. Grindstaff PD, Kreider R, Bishop R, et al. Effects of creatine supplementation on repetitive sprint performance and body composition in competitive swimmers. Int J Sports Nutr 1997;7:330-46.

18. Peyrebrune MC, Nevill ME, Donaldson FJ, et al. The effects of oral creatine supplementation on performance in single and repeated sprint swimming. J Sports Sci 1998;16:271-9.

19. Balsom PD, Harridge SD, Soderlund K, et al. Creatine supplementation per se does not enhance endurance exercise performance. Acta Physiol Scand 1993;149:521-3.

20. Vandenberghe K, Goris M, Van Hecke P, et al. Long-term creatine intake is beneficial to muscle performance during resistance training. J Appl Physiol 1997;83:2055-63.

21. Becque MD, Lochmann JD, Melrose DR. Effects of oral creatine supplementation on muscular strength and body composition. Med Sci Sports Exerc 2000;32:654-8.

22. Stout JR, Eckerson J, Noonan D, et al. The effects of a supplement designed to augment creatine uptake on exercise performance and fat-free mass in football players. Med Sci Sports Exerc 1997;29:S251 [abstract].

23. Felber S, Skladal D, Wyss M, et al. Oral creatine supplementation in Duchenne muscular dystrophy: a clinical and 31P magnetic resonance spectroscopy study. Neurol Res 2000;22:145-50.

24. Walter MC, Lochm�H, Reilich P, et al. Creatine monohydrate in muscular dystrophies: A double-blind, placebo-controlled clinical study. Neurology 2000;54:1848-50.

25. Tarnopolsky MA, Roy BD, MacDonald JR. A randomized, controlled trial of creatine monohydrate in patients with mitochondrial cytopathies. Muscle Nerve 1997;20:1502-9.

26. Sipila I, Rapola J, Simell O, et al. Supplementary creatine as a treatment for gyrate atrophy of the choroid and retina. N Engl J Med 1981;304:867-70.

27. Tarnopolsky M, Martin J. Creatine monohydrate increases strength in patients with neuromuscular disease. Neurology 1999;52:854-7.

28. Andrews R, Greenhaff P, Curtis S, et al. The effect of dietary creatine supplementation on skeletal muscle metabolism in congestive heart failure. Eur Heart J 1998;19:617-22.

29. Gordon A, Hultman E, Kaijser L, et al. Creatine supplementation in chronic heart failure increases skeletal muscle creatine phosphate and muscle performance. Cardiovasc Res 1995;30:413-8.

30. Earnest CP, Almada AL, Mitchell TL. High-performance capillary electrophoresis-pure creatine monohydrate reduces blood lipids in men and women. Clin Sci 1996;91:113-8.

31. Volek JS, Duncan ND, Mazzetti SA, et al. No effect of heavy resistance training and creatine supplementation on blood lipids. Int J Sport Nutr Exerc Metab 2000;10:144-56.

32. Silber ML. Scientific facts behind creatine monohydrate as a sports nutrition supplement. J Sports Med Phys Fitness 1999;39:179–88 [review].

33. Greenhaff PL. The nutritional biochemistry of creatine. J Nutr Biochem 1997;8:610–8.

34. Vandenberghe K, Goris M, Van Hecke P, et al. Long-term creatine intake is beneficial to muscle performance during resistance training. J Appl Physiol 1997;83:2055–63.

35. Becque MD, Lochmann JD, Melrose DR. Effects of oral creatine supplementation on muscular strength and body composition. Med Sci Sports Exerc 2000;32:654–8.

36. Hultman E, Soderlund K, Timmons J, et al. Muscle creatine loading in man. J Appl Physiol 1996;81:232–7.

37. Green AL, Hultman E, Macdonald IA, et al. Carbohydrate ingestion augments skeletal muscle creatine accumulation during creatine supplementation in man. Am J Physiol 1996;271:E821–6.

38. Feldman EB. Creatine: a dietary supplement and ergogenic aid. Nutr Rev 1999;57:45–50.

39. Vandenberghe K, Gills N, Van Leemputte M, et al. Caffeine counteracts the ergogenic action of muscle creatine loading. J Appl Physiol 1996;80:452–7.

40. Juhn MS, O’Kane JW, Vinci DM. Oral creatine supplementation in male collegiate athletes: a survey of dosing habits and side effects. J Am Diet Assoc 1999;99:593–5.

41. Sewell DA, Robinson TM, Casey A, et al. The effect of acute dietary creatine supplementation upon indices of renal, hepatic and haematological function in human subjects. Proc Nutr Soc 1998;57:17A.

42. Poortmans JR, Auquier H. Renaut V, et al. Effect of short-term creatine supplementation on renal responses in men. Eur J Appl Physiol Occup Physiol 1997;76:566–7.

43. Earnest C, Almada A, Mitchell T. Influence of chronic creatine supplementation on hepatorenal function. FASEB J 1996;10:4588.

44. Almada A, Mitchell T, Earnest C. Impact of chronic creatine supplementation on serum enzyme concentrations. FASEB J 1996;10:4567.

45. Poortmans JR, Francaux M. Long-term oral creatine supplementation does not impair renal function in healthy athletes. Med Sci Sports Exerc 1999;31:1108–10.

46. Koshy KM, Griswold E, Schneeberger EE. Interstitial nephritis in a patient taking creatine. N Engl J Med 1999;340:814–5 [letter].

47. Pritchard NR, Kaira PA. Renal dysfunction accompanying oral creatine supplements. Lancet 1998;351:1252–3 [letter].

48. Hultman E, Soderlund K, Timmons J, et al. Muscle creatine loading in man. J Appl Physiol 1996;81:232–7.

49. Vandenberghe K, Goris M, Van Hecke P, et al. Long-term creatine intake is beneficial to muscle performance during resistance training. J Appl Physiol 1997;83:2055–63.

50. Juhn MS, Tarnopolsky M. Potential side effects of oral creatine supplementation: a critical review. Clin J Sport Med 1998;8:298–304 [published erratum appears in Clin J Sport Med 1999;9:62].

NHE


PS - Healthnotes.com has information on many different supplements. However, the site cannot be accessed directly since it is sold to subscribers which then provide access to their users. One such subscriber which provides free access to Healthnotes.com's information is http://www.newseasonsmarket.com.
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