Dopamine neurons containing

Figure 3. Sketch of DDC-expressing neurons in the Drosophila larval CNS. The CNS consists of brain lobes and a segmented ventral ganglion. Filled circles represent dopamine cells open circles represent serotonin cells grayed circles represent DDC cells that contain no detectable tyrosine hydroxylase or serotonin immunoreactivity, indicating that these cells may produce neither transmitter (Lundell and Hirsh, 1994). M, medial dopamine neurons VL, ventrolateral serotonin neurons DL, dorsolateral dopamine neurons. The hatched rectangle shows the region of the ventral ganglion that is shown in Figures 4 and 6.

Figure 4. DDC (A), serotonin (B), and tyrosine hydroxylase (C) immunore-activity in the posterior region of a wild-type Drosophila ventral ganglion. Tyrosine hydroxylase (TH) encodes the rate-limiting step in dopamine biosynthesis and is a marker for dopamine cells. B and C are the same CNS assayed for both serotonin and TH. M, medial dopamine neurons VL, ventrolateral serotonin neurons DL, dorsolateral dopamine neurons. Short unmarked arrows in C show vacuolated cells that do not contain DDC immunoreactivity. The immunoreactivity in these cells may represent a nonspecific cross-reactivity of the rat TH antibody. The length bar in A is 50 pM. The images are confocal projections generated on a Molecular Dynamics-2000 confocal laser scanning microscope.

It is widely accepted that Parkinson s disease primarily results from degeneration of pigmented neurons in the substantia nigra (Gibb 1998). This causes a loss of nigrostriatal projections and lack of dopamine modulation in the striatum. In addition to loss of neurons, many of the remaining neurons contain Lewy bodies. 

A potentially promising, although very controversial, approach to the treatment of Parkinson s disease is replacement of dopaminergic neurons. The grafting of fetal substantia nigra tissue, which contains the dopamine neurons, into the striatum of parkinsonian patients has been modestly successful. The procedure will remain experimental, however, until the many practical problems and ethical issues associated with the use of fetal tissue are resolved. The discovery of pluripotent stem cells is also being viewed as a possible way of developing dopamine neurons for transplant purposes. 

A stereotyped compulsive behavior is induced both in humans and in laboratory animals by amphetamines. This provided the basis for a method that has been used to measure the action of drugs on amphetamine-sensitive centers of the brain. A lesion in the nigrostriatal bundle on one side of a rat brain was made by injection of a neurotoxic compound such as 6-hydroxydopamine. This caused degeneration of dopamine-containing neurons on one side of the brain. When rats that had been injured in this way were given amphetamines, they developed a compulsive rotational behavior. Administration of chlorpromazine and several other antipsychotic drugs neutralized this behavior and in direct proportion to the efficacy in clinical use, an observation that also supports the theory that schizophrenia involves overactivity of dopamine neurons. 

There is a third enzyme expressed in norepinephrine neurons that converts dopamine into more norepinephrine therefore, this enzyme is not expressed by dopamine neurons. The enzyme is stored within the synaptic vesicles and lies in wait for the entry of dopamine molecules once they have been synthesized in the cytoplasm of the neuron. In addition to this third enzyme, the vesicles contain copper and the anti-oxidant ascorbic acid, also known as Vitamin C. Copper is required for the enzyme to function appropriately. The ascorbic acid maintains the integrity of norepinephrine within the vesicle in the same way that ascorbic acid added to processed meats such as hotdogs... 

Hokfelt T, Skirboll L, Rehfeld JF, Goldstein M, Markey K, Dann O (1980b) A subpopulation of mesencephalic dopamine neurons projecting to limbic areas contains a cholecystokinin-like peptide evidence from immunohistochemistry combined with retrograde tracing. Neuroscience 5 2093-2124. 

Robertson GS, Vincent SR, Fibiger HC (1990) Striatonigral projection neurons contain D, dopamine receptor-activated c-fos. Brain Res 523 288-290. 

Dopaminergic neurons contain neuromelanin, a pigment composed of lipofus-cin along with a complex mixture of polymers of the various catecholamines, metal ions, cysteine, and possibly other substances (A4). This waste pigment is presumed to be derived from the oxidation of dopamine and other catecholamines to produce quinones, semiquinones, and quinhydrones, some of which undergo... 

Ferritins can store excess iron and release it when required for cellular processes. In addition, neuromelanin (NM), which is an organic polymer consisting of dihydroxyindole and benzothiazine units which are products of dopamine metabolism, is also present and is able to bind a number of metals, e.g., copper and iron. In oligodendrocytes, iron is bound to both H- and L-chain ferritin, in microglia to L-ferritin, while neurons contain mostly neuromelanin. In contrast, astrocytes contain hardly any ferritin. As to the movement of iron between different brain regions, this in the main remains unclear. It is thought that transferrin and ferritin may be important, since mRNA receptors for these iron proteins are detectable in grey matter and white matter, respectively. The fate of non-transferrin-bound iron, which may cross the BBB, remains unclear. 

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