Neuron tracts

Topical application of MnCl2 has also been investigated [36]. Application of MnCl2 to the naris of mice allowed for visualization of the olfactory pathway as the Mn2+ ions were transported up the neuronal tract. Administration of this agent did not affect the ability of the mice to detect odors and the amount of manganese(II) accumulated in tissue was below the intracellular toxicity levels. Injection of MnCl2 into the aqueous humor of the eyes of mice demonstrated enhancement of the vitreal humor and the optic tract. 

Most neurons in the CNS receive both EPSP and IPSP input. Thus, several different types of neurotransmitters may act on the same neuron, but each binds to its own specific receptor. The overall resultant action is due to the summation of the individual actions of the various neurotransmitters on the neuron. The neurotransmitters are not uniformly distributed in the CNS but are localized in specific clusters of neurons whose axons may synapse with specific regions of the brain. Many neuronal tracts thus seem to be chemically coded, and this may offer greater opportunity for selective modulation of certain neuronal pathways. 

FIGURE 11.13 Typical infiltration of malignant tumor cells along a neuronal tract (outlined by dotted lines). (Adapted from R A. Mettler, J. Neuropathol. Exp. Neurol. 1955,14, 115-141.)... 

Malignant brain tumor cells have a tendency to infiltrate throughout the brain along neuronal tracts (Figure 11.13). If tumor cells invade the other hemisphere through neuronal tracts that traverse the corpus callosum, chemotherapy is the only available treatment. Other modalities, including BNCT, are definitely contraindicated. 

More recently the use of the histofluorescence method for the localization of brain amines led to the finding that DA, NA and 5HT are present in the brain not merely in a characteristic distribution by region but in DA, NA and 5HT neuronal tracts [9], each one containing a specific amine. Furthermore, it has been shown that electrical stimulation of the cell bodies of the NA [10], DA [10] or 5HT [11] neurones results in depletion of the corresponding amine at the nerve terminals. Also, experiments using microelectrophoretic application of... 

Neuronal tracts can be labeled with the mAb 1D4 (DSHB 1 55-1 75, provided by Corey Goodman) directed against Fasciclin II (FasII), a membrane-bound adhesion molecule. The FasII landmark system in the ventral nerve cord (VNC) of the larva is originally described by Landgraf et al. [50] see also [51]. In the VNC, FasII-positive tracts provide a sort of 3D grid as they run... 

ALS is a disorder of the motor neurons and the cortical neurons that provide their input. The disorder is characterized by rapidly progressive weakness and muscle atrophy. Most affected patients die of respiratory compromise and pneumonia after 2 to 3 years. There is prominent loss of motor neurons in the spinal cord and brainstem although the oculomotor neurons are spared. Large pyramidal motor neurons in layer V of motor cortex, which are the origin of the descending corticospinal tracts, are also lost. 

The dopamine precursor l-DOPA (levodopa) is commonly used in TH treatment of the symptoms of PD. l-DOPA can be absorbed in the intestinal tract and transported across the blood-brain barrier by the large neutral amino acid (LNAA) transport system, where it taken up by dopaminergic neurons and converted into dopamine by the activity of TH. In PD treatment, peripheral AADC can be blocked by carbidopa or benserazide to increase the amount of l-DOPA reaching the brain. Selective MAO B inhibitors like deprenyl (selegiline) have also been effectively used with l-DOPA therapy to reduce the metabolism of dopamine. Recently, potent and selective nitrocatechol-type COMT inhibitors such as entacapone and tolcapone have been shown to be clinically effective in improving the bioavailability of l-DOPA and potentiating its effectiveness in the treatment of PD. 

In the gastrointestinal tract, drugs or toxins, as well as mechanical stimulation, induce emesis by activation of sensory receptors on afferent neurons in the vagus and sympathetic nerves. Information is relayed to the vomiting centre via the nucleus tractus solitarius... 

The nigrostriatal tract is one of the four main dopaminergic pathways in the central nervous system. About 75% of the dopamine in the brain occurs in the nigrostriatal pathway with its cell bodies in the substantia nigra, whose axons project in the corpus striatum. Degeneration of the dopaminergic neurons in the nigrostriatal system results in Parkinsons disease. 

On the pathophysiological side, hyperactive nNOS has been implicated in A/-methyl-D-aspartate (NMDA)-receptor-mediated neuronal death in cerebrovascular-stroke. Some disturbances of smooth muscle tone within the gastrointestinal tract (e.g., gastroesophageal reflux disease) may also be related to an overproduction of NO by nNOS in peripheral nitrergic nerves. 

Figure 1.8 Some basic neuronal systems. The three different brain areas shown (I, II and III) are hypothetical but could correspond to cortex, brainstem and cord while the neurons and pathways are intended to represent broad generalisations rather than recognisable tracts. A represents large neurons which have long axons that pass directly from one brain region to another, as in the cortico spinal or cortico striatal tracts. Such axons have a restricted influence often only synapsing on one or a few distal neurons. B are smaller inter or intrinsic neurons that have their cell bodies, axons and terminals in the same brain area. They can occur in any region and control (depress or sensitise) adjacent neurons. C are neurons that cluster in specific nuclei and although their axons can form distinct pathways their influence is a modulating one, often on numerous neurons rather than directly controlling activity, as with A . Each type of neuron and system uses neurotransmitters with properties that facilitate their role...

D2 Mostly in striatum, nucleus accumbens and olfactory tubercle but also on neuron cell bodies in substantia nigra and ventral tegmentum where they are the autoreceptors for locally (dendritic) released DA. The loss of specific D2 antagonist binding in the striatum after lesions of the afferent nigro-striatal tract indicates their presynaptic autoreceptor role on terminals there. Other lesion studies have also established D2 receptors on other inputs such as the cortico striatal tract. 

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