Neuronal metabolism, and

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... 

Adrenaline (epinephrine) is a catecholamine, which is released as a neurotransmitter from neurons in the central nervous system and as a hormone from chromaffin cells of the adrenal gland. Adrenaline is required for increased metabolic and cardiovascular demand during stress. Its cellular actions are mediated via plasma membrane bound G-protein-coupled receptors. 

Substantia nigra pars reticulata is the area with highest neuronal activity and metabolic rate in the brain. This region also shows highest expression rates of SUR1/ Kir6.2 channels. These KATP channels are present... 

MAO converts dopamine to DOPAC (3,4-dihydrox-yphenylacetic acid), which can be further metabolized by COMT to form homovanillic acid (HVA). HVA is the main product of dopamine metabolism and the principal dopamine metabolite in urine. Increased neuronal dopaminergic activity is associated with increases in plasma concentrations of DOPAC and HVA. COMT preferentially methylates dopamine at the 3 -hydroxyl position and utilizes S-adenosyl-L-methio-nine as a methyl group donor. COMT is expressed widely in the periphery and in glial cells. In PD, COMT has been targeted since it can convert l-DOPA to inactive 3-OMD (3-O-methyl-dopa). In the presence of an AADC inhibitor such as carbidopa, 3-OMD is the major metabolite of l-DOPA treatment. 

Like other cells, a neuron has a nucleus with genetic DNA, although nerve cells cannot divide (replicate) after maturity, and a prominent nucleolus for ribosome synthesis. There are also mitochondria for energy supply as well as a smooth and a rough endoplasmic reticulum for lipid and protein synthesis, and a Golgi apparatus. These are all in a fluid cytosol (cytoplasm), containing enzymes for cell metabolism and NT synthesis and which is surrounded by a phospholipid plasma membrane, impermeable to ions and water-soluble substances. In order to cross the membrane, substances either have to be very lipid soluble or transported by special carrier proteins. It is also the site for NT receptors and the various ion channels important in the control of neuronal excitability. 

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. 

Neuropathic pain states are thought to be generated in the peripheral sensory neurons by events within the nerve itself and so are independent of peripheral nociceptor activation. Damage to peripheral nerves can be caused by a number of pathological, metabolic and viral causes. According to the terminology guide of the International... 

HMIT is a H+-coupled myo-inositol symporter. High levels of its expression are observed in neurons and glia of hippocampus, hypothalamus, cerebellum and brainstem. Since myo-inositol is a precursor for phosphatidyl inositol, which itself is a critical regulator of many neuronal processes (Ch. 20), HMIT regulation is possibly involved in various mood and behavior patterns that are affected by inositol metabolism and by pharmacologic agents that modify inositol metabolism (see Chs 54 and 55). 

A variety of different types of tissue preparation are used to study neurosecretion and synaptic transmission. A classical preparation is the frog NMJ (discussed below). The brain slice has been used for many years for biochemical studies of CNS metabolism and is a useful preparation for electrophysiological studies of synaptic transmission in the CNS. Slices can be oriented to maintain the local neuronal circuitry and can be thin, 0.3 mm, to minimize anoxia. The transverse hippocampal slice is widely used as an electrophysiological preparation to study synaptic plasticity (see Ch. 53). Primary cultures of neurons from selected CNS areas and sympathetic ganglia are also frequently used. They permit excellent visual identification of individual neurons and control of the extracellular milieu, but the normal neuronal connections are disrupted. 

Not included are other protein kinases present in diverse tissues, including brain, that play a role in generalized cellular processes, such as intermediary metabolism, and that may not play a role in neuron-specific phenomena. CAK, CDK-activating kinase ... 

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 ... 

The neuregulins also act on Schwann cells to stimulate motility and migratory activity. It is postulated that this interaction provides a mechanism by which neurons can influence glial metabolism and behavior, which are important both in development and for peripheral nerve regeneration. 

Edmond, J., Robbins, R. A., Bergstrom, J. D. etal. Capacity for substrate utilization in oxidative metabolism by neurons, astrocytes, and oligodendrocytes from developing brain in primary culture. J. Neurosci. Res. 18 551-561, 1987. 

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