Neuron cytoplasm

Catecholamine biosynthesis begins with the uptake of the amino acid tyrosine into the sympathetic neuronal cytoplasm, and conversion to DOPA by tyrosine hydroxylase. This enzyme is highly localized to the adrenal medulla, sympathetic nerves, and central adrenergic and dopaminergic nerves. Tyrosine hydroxylase activity is subject to feedback inhibition by its products DOPA, NE, and DA, and is the rate-limiting step in catecholamine synthesis the enzyme can be blocked by the competitive inhibitor a-methyl-/)-tyrosine (31). 

Two separate lines of research led to the proposal that transmitter released in response to neuronal excitation is derived from a vesicle-bound pool rather than from the neuronal cytoplasm. One piece of evidence came from electron microscopy which... 

Experiments of this kind have provided a great deal of evidence in favour of exocytotic release of vesicular noradrenaline. For example, by administering reserpine (which causes noradrenaline to leak out of the vesicles into the cytoplasm) together with an inhibitor of the enzyme monoamine oxidase (which will prevent metabolism of cytoplasmic noradrenaline), it is possible to redistribute the noradrenaline stored within nerve terminals because it leaks from the vesicles but is preserved within the neuronal cytoplasm. Under these conditions, the total amount of transmitter in the terminals is unchanged but impulse-evoked release rapidly diminishes. 

The recovery of neurotransmitters from synaptic clefts and their storage in cytoplasmic vesicles is accomplished by the tandem actions of the secondary transporters in plasma and vesicular membranes. Sodium-dependent symporters mediate neurotransmitter reuptake from synaptic clefts into neurons and glia, whereas proton-dependent antiporters concentrate neurotransmitters from neuronal cytoplasm into synaptic vesicles (Fig. 5-13). 

Johnson ME et al Effect of local anesthetic on neuronal cytoplasmic calcium and plasma membrane lysis (necrosis) in a cell culture model. Anesthesiology 2002 97 1466. [PMID 12459673]... 

FIGURE 20.7 Creutzfeldt-Jakob disease (CJD). Biopsy specimen from the cerebral frontal lobe of an elderly man who had displayed progressive behavioral and memory changes for a few weeks. Patches of vacuoles and synaptic depletion can be seen in the cortical gray matter. Each tiny brown dot is a synapse in the neuropil stained with synaptophysin. Vacuoles in neuronal cytoplasm indent their nuclei. (Anti-synaptophysin with hematoxylin counterstain.)... 

Myelin associated glycoprotein neuronal cytoplasmic protein 3 (MAG/Ncp 3)... 

MAG is one of a set of cell-surface glycoproteins expressed by myelin-forming cells which have been hypothesized to mediate the apposition of the myelin sheath to the axon. Two forms of MAG are known which, similarly to NCAM, differ in the intracytoplasmic domain as a result of alternative splicing. The carboxy-terminal 318 amino acids of MAG are identical to the partial sequence so far obtained of a protein that has been designated as rat neuronal cytoplasmic protein 3 [184], However, the latter was previously believed to be a neuropeptide precursor and to be expressed in specific groups of neurons rather than in glial cells. The reason for this discrepancy is unclear. 

The botulinum toxins are large polypeptide molecules (approximately 150 kDa) which contain Zn ions. They are synthesised as single polypeptides which are cleaved by endogenous protease action to yield the active forms, each of which consists of two polypeptide chains linked by a disulphide bond. The larger of the two chains, denoted the heavy (H) chain, has a mass of approximately 95 kDa and the smaller, the light (L) chain, a mass of approximately 50 kDa. The structure is illustrated in Figure 1. The H chain is composed of two domains of similar mass the C-terminal domain (He) is responsible for the specificity of binding of the toxin to peripheral motoneurones and the N-terminal domain (Hn) for penetration of the toxin into the neuronal cell. In the neuronal cytoplasm, the L chain is released by proteolysis and it is this subunit which is responsible for the disruption of the exocytotic apparatus, which causes blockade of transmitter release. 

Fig. 5 Reverse transcriptase-PCR analysis of NnAChR messenger RNA (mRNA) in rat vagal pulmonary sensory neurons. Cytoplasm of 20 isolated pulmonary sensory neurons was collected into a single PCR tube. One-step Reverse transcriptase-PCR and a nested PCR were carried out to detect the presence of nicotinic mRNA subunits. The nested PCR products were run on a 1% agarose gel and stained with ethidium bromide. M 100-bp DNA marker. (From Gu et al. 2008, with permission)...

In three cases of Banker et al. (1962) neuropathological changes consisted of a mild neuronal cytoplasmic accumulation of a glycolipid, nerve cell loss, and neuro-nophagia in the brain stem nuclei. In addition, there were foci of nerve cell loss in layers three and five of the cortex as well as infiltrates of Gaucher cells and microglia in these zones. 

Fig. 4 Single immunoperoxidase staining for LC3B at P11, PI 7, and P30. At P11, the ML of control rats is intensely immunopositive (a). After treatment with platinum compounds, there are no obvious differences in immunoreactivity (b, c). At PI 7, there is a reduction of immunoreactivity in Purkinje cells of controls (d) and that becomes much more evident after treatment with cisPt (e) and PtAcacDMS (f). At P30, immunoreactivity has completely disappeared from the ML. In parallel, a weak labeling appears in the Purkinje neuron cytoplasm and main dendrites (g-i). Abbreviations-. EGL external granular layer, IGL internal granular layer, ML molecular layer. Scale bars 50 pm (e-i) 100 pm (a-f)...

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