Neuronal metabolism

Liu Y, Jones M, Hingtgen CM, Bu G, Laribee N, Tanzi RE, Moir RD, Nath A, He JJ (2000) Uptake of HIV-1 tat protein mediated by low-density lipoprotein receptor-related protein disrupts the neuronal metabolic balance of the receptor ligands. Nat Med 6 1380-1387... 

In the face of the failure of rational approaches in the treatment of AzD it is perhaps not surprising that there have been many less rational ones. These include the use of vasodilators and nootropics. The former, such as hydergine, a mixture of ergot alkaloids, are intended to increase cerebral blood flow and neuronal metabolism despite some reduction in blood pressure, while the latter, like piracetam, are metabolic stimulants that increase cerebral metabolism and ATP production. Neither are of proven value in AzD. 

Glutamate (Glu) is the most abundant amino acid in the central nervous system (CNS). It serves many functions as an intermediate in neuronal metabolism, e.g., as a precursor for GABA. About 30% of the total glutamate in the brain functions as the major excitatory neurotransmitter. 

Another important difficulty in the evaluation of the correct activity values for enzymes involved in energy metabolism in neurons resides in the fact that opposite processes may occur simultaneously, like the reduction of neuronal metabolism and compensatory enhancement in glial activity. The altered activities of some glycolytic enzymes in brain homogenates represent a net-effect, and it is unclear how the energy state (ATP level) of the neurons is perturbed if the metabolic activation is... 

This suggests that after 120 min of MCAO, neuronal metabolism in the ischemic core is not rescued by 120 min of reperfiision whereas neuronal integrity is preserved in the penumbral zone. 

Chart 1.2 Neuronal metabolism of dopamine. Dopamine (1) 3,4-dihydroxyphenyl acetaldehyde (4) 3,4-dihydroxyphenylacetic acid (DOPAC, 5) homovanillic acid (HVA, 6) 3-methoxytyramine (3-MT, 7) 3-methoxy-4-hydroxyphenyl acetaldehyde (8) MAO, monoamine oxidase AD, aldehyde dehydrogenase COMT, catechol-O-... 

A majority of these agents have been developed initially as peripheral vasodilators which have then been tested for their ability to increase cerebral blood flow on quite empirical grounds. The second group contains those which stimulate neuronal metabolism, the resultant increase in local perivascular CO2 production consequently causing vasodilatation. The former group will be referred to as Vasotropic dilators and the latter as Cerebrometabolic stimulants. ... 

Since iron is involved in many central nervous system processes that could affect infant behaviour and development, iron deficiency has adverse effects on brain development, both pre- and post-natal. In various epidemiological studies, it is reported that children with iron-deficiency anaemia have poorer performances on tests of some specific cognitive function. Animal experiments have identified some of the defects of reduced iron availability on brain function, which include post-translational changes (which result in a failure of iron incorporation into protein structures which are subsequently degraded), vulnerability of the developing hippocampus (with loss of the neuronal metabolic marker cytochrome c oxidase), and altered dendritic stmcture. Iron deficiency will also have a direct effect on myelin, including a decrease in myelin lipids and proteins, as well as neurotransmitter systems, since iron... 

At present there are no specific glycine receptor agonists more potent than glycine Itself, and there are no agents which can specifically alter the neuronal metabolism, uptake or release of this amino acid making it difficult to selectively manipulate this system. 

NOS is found in certain amacrine cells in the retina (Sharma et al., 1997 Sharma et al., 2001). NOS produces NO, and the interaction of NO with the superoxide radical is imphcated in normal neuronal metabolism as well as neurodegeneration. 

Zeevalk GD, Nicklas WJ. 1992. Evidence that the loss of the voltage-dependent Mg block at the N-methyl-D-aspartate receptor underlies receptor activation during inhibition of neuronal metabolism. J Neurochem 59 1211-1220. 

Shank RP, Campbell GLeM (1984a) a-Ketoglutarate and malate uptake and metabolism by synaptosomes further evidence for an astrocyte-to-neurons metabolic shuttle. J Neurochem 42 1153-1161. 

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