Brain development choline

All nutrients are important for neuronal cell growth and development, but manipulation of some nutrients appears to cause more effects than others. Protein, energy, iron, zinc, selenium, iodine, folate, vitamin A, choline, and LC-PUFAs are nutritional components that influence early brain development with measurable clinical effects in humans and animal models (Georgieff and Rao, 2001). A nutrient that promotes normal brain development at one time and concentration may be toxic at another time or concentration. Many nutrients, such as iron, are regulated within a very narrow range because deficiency and toxicity have profound effects in brain development. 

The anaemia in B deficiency is caused by an inability to produce sufficient of the methylating agent S-adenosyhnethionine. This is required by proliferating cells for methyl group transfer, needed for synthesis of the deoxythymidine nucleotide for DNA synthesis (see below and Chapter 20). This leads to failure of the development of the nucleus in the precursor cells for erythrocytes. The neuropathy, which affects peripheral nerves as well as those in the brain, is probably due to lack of methionine for methyl transfer to form choline from ethanolamine, which is required for synthesis of phosphoglycerides and sphingomyelin which are required for formation of myelin and cell membranes. Hence, the neuropathy results from a... 

Neonatal treatment with chlorpromazine or lysergic acid diethylamide (LSD) in rats resulted in lowered brain 5HT (5 Hydroxy Tryptamine) levels in adulthood (ref. 97). Perinatal methadone treatment in rats was shown to decrease not only total brain weight, but also to retard synaptic development of central 5-HT, DA and NA neurons (ref. 98). Early diazepam treatment was found to affect uptake of choline in 60 day old male rats (but not in females) and uptake of GABA (Gamma Amino Butyric Acid) and 5HT in 60 day old females (ref. 99). 

A more complex biosensor for acetylcholine has been developed by Larsson et al. [154]. Three enzymes, AChE, ChOX, and HPR, have been coimmobilized in an Os-based redox polymer on solid graphite electrodes. After a careful optimization of the immobilization procedure, the biosensor, inserted into a flow cell of very small volume, was integrated into a flow injection system, and some samples of microdialysate, taken from rat brains before and after stimulation with KCl, were analysed. Even if a clear increase in signal could be noted, it was not possible to distinguish whether it was due to an increase in choline or in acetylcholine, since the biosensor responded to both metabolites. 

A continuous monitoring of acetylcholine by microdialysis, avoiding a chromatographic separation step, could be achieved by the development of a dual biosensor having one part sensitive to choline, the other one to acetylcholine. In this case, the concentration of the latter could be obtained by subtraction, if the sensitivity, stability and rejection of interference by both biosensors turned out to be suitable for the concentration levels typical of the brain. 

Mobley, W. C., Rutkowski, J. L., Tennekoon, G. I., Gemski, J., Buchanan, K., and Johnston, M. V., Nerve growth factor increases choline acetyltransferase activity in developing basal forebrain neurons, Brain Res., 387, 53, 1986. 

Grothe, C., Wewetzer, K., Lagrange, A., and Unsicker, K., Effects of basic fibroblast growth factor on survival and choline acetyltransferase development of spinal cord neurons, Dev. Brain Res., 62, 257, 1991. 

Brain. - An historical review of developments in the field of cerebral blood flow and metabolism has been produced with 34 references. The use of NMR and magnetic resonance imaging in the study of function and dysfunction in the neonatal brain has been reviewed with 40 references. The potential of and NMR in the assessment of cerebral metabolism in experimental models and human hydrocephalus has been reviewed with 110 references.A review of the applications of C-labelling to studies of the human brain has been produced with 90 references. The detection of choline-containing phospholipids in acute and chronic neurodegeneration has been reviewed with 231 references.The role of and NMR in the study of schizophrenia has been reviewed in two parts. A review of the use of NMR in the study of phenylketonuria has been produced with 26 references and comments on the text have also been published. 

Gould E, Butcher LL (1987) Transient expression of choline acetyltransferase-like immunoreactivity in Purkinje cells of the developing rat cerebellum. Dev. Brain Res., 34, 30,3-306. 

Despite the drawbacks of the cholinergic hypothesis, this idea has guided most of the researchers involved with AD and enormous resources have been invested in developing compounds that would directly (nicotinic and M, selective muscarinic agonists) or indirectly (acetylcholinesterase inhibitors, M2 selective muscarinic antagonists, acetylcholine releasers, high affinity choline uptake inhibitors) increase the level of cholinergic transmission in the brain. 

Tang, J, Carr, R. L., and Chambers, J. E, (2003). The effects of repeated oral exposures to methyl parathion on rat brain choline.sterase and muttcarinic receptors during postnatal development. Toxicol, Sci. 76, 400-406. 

Bus. J- S.. and Gibson, J. E, (1974). Bidrin Perinatal toxicity and effect.s on the development of brain acetylcholinesterase and choline acetyltransferasc in mice. Food Cosmet. To. icol. 12, 313-322. 

---