Methylation brain function

Before complexes can be used in nuclear medicine, especially for brain function studies, in vivo reactivity has to be imposed upon them. Retention in the brain is necessary for perfusion imaging. This can be achieved by substituents on the ligand that bind them to binding sites in the brain. N-alkylation with methyl and other alkyl groups led to the class of complexes shown in Fig. 19. Upon complexation to technetium, the IV-alkyl substituent can assume a syn or anti configuration with respect to the oxo ligand, as proved by X-ray crystal... 

Aspartame, N-a-L-aspartyl-L-phenylalanine methyl ester, trade names NutraSweet , and Aspartil , is a dipeptide derivative. Like dipeptides aspartame is metabolised into the constituents, i.e. amino acids and methanol. Therefore studies into the metabolic behaviour and the fate of metabolites were carried out. Levels of blood aspartate and glutamate were measured after intake of high aspartame doses. Changes were transient and allegations of influences of high aspartame levels on brain function could never be verified. 

Dihydroxyphenylalanine (DOPA) (99) is produced by tyrosine hydroxylase-catalyzed hydroxylation of Tyr. Recent interest in the use of [18F]-6-F-DOPA (100) as a PET scanning agent for regional dopaminergic brain function is based on its conversion, in the brain, to [,8F]-6-F-dopamine (101)161. The fact that fluorine in the 6-position of DOPA, dopamine and other catecholamines retards methylation by catechol-O-methyl transferase presumably increases the biological half-life of the tracer. In contrast, fluorine in the 5-position increases the rate of methylation162. 

Methyl mercury exposure in utero is associated with reduced brain function and a doubling of the risk of heart attacks and other cardiovascular problems. 

Structural changes of the brain, functional changes and more subtle effects such as impairment of sensory or cognitive systems were also a demonstrated burden in several animal experiments after in-utero exposure to methyl mercury (EPA... 

Garden City, NY, Medical Examination Publishing, 1981 Snyder SH, Faillace L 2,3-Dimethoxy-4-methyl-amphetamine (STP) a new hallucinogenic drug. Science 1388 669-670, 1967 Spielewoy C, Markou A Withdrawal from chronic phencyclidine treatment induces long-lasting depression in brain reward function. Neuropsychopharmacology 28 1106-1116,2003... 

The mink Mustela vision) is a piscivorous mammal that also has been exposed to relatively high dietary levels of methyl mercury in North America in recent times. In a Canadian study, mink trapped in Yukon territory, Ontario, and Nova Scotia were analyzed for levels of mercury and abundance of muscarinic, cholinergic and dopaminergic receptors in the brain (Basu et al. 2005). A correlation was found between total Hg levels and abundance of muscarinic receptors, but a negative correlation was found between total Hg and abundance of dopaminergic receptors. Thus, it was suggested that environmentally relevant concentrations of Hg (much of it in methyl form) may alter neurochemical function. The highest levels of mercury contamination were found in mink from Nova Scotia that had a mean concentration of total Hg of 5.7 pg/g in brain, 90% of which was methyl mercury. 

This list is not intended to be comprehensive but to indicate the wide array of neuronal proteins regulated by phosphorylation. Some of the proteins are specific to neurons but most are present in many cell types in addition to neurons and are included because their multiple functions in the nervous system include the regulation of neuron-specific phenomena. Not included are the many phosphoproteins present in diverse tissues, including brain, that play a role in generalized cellular processes, such as intermediary metabolism, and that do not appear to play a role in neuron-specific phenomena. NMDA, N-methyl-D-aspartate CREB, cAMP response element-binding proteins STAT, signal-transducing activators of transcription ... 

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