Fig.1 Molecular factors involved in the development of ventral midbrain (VM) Dopaminergic (DA) neurons. (Hegarty, 2013)
Overview of Dopaminergic Neurons
Previous research has shown that the hypothalamus and substantia nigra are the main sources of dopamine production in the brain. In adult mammals, dopamine synthesized in the hypothalamus, mostly in neurons that localized in the insert zones, the periventricular and arcuate nuclei, is involved in neuroendocrine regulation as a) a neurotransmitter controlling the secretory activity of peptidergic target neurons, b) a neuromodulator regulating the release of neurohormones from neighboring peptidergic axons into the median eminence, and c) a neurohormone passing via the hypophyseal portal circulatory system to the anterior lobe of the hypophysis, where it inhibits prolactin secretion.
Dopaminergic Neurons and Parkinson's Disease (PD)
The depleted dopamine levels, dopaminergic neurons loss, and intraneuronal cytoplasmic inclusions termed as Lewy Bodies (LB) in surviving substantia nigra pars compacta (SNpc) neurons are the pathological hallmarks of PD. The SNpc contains the soma of nigrostriatal neurons and projects them to the putamen. The pattern of SNpc cell loss appears parallel to the expression levels of the dopamine transporter (DAT) transcript and is consistent with the finding that dopamine loss is most pronounced in the dorsolateral putamen, the main site of projection for these neurons. At the onset of symptoms, putamen dopamine is depleted 80%, and 60% of SNpc dopaminergic neurons have already been lost. However, the cell bodies of mesolimbic dopaminergic neurons adjacent to SNpc are affected to a limited extent in PD. Consequently, there is significantly less depletion of dopamine in the caudate. Thus, the selective loss of dopamine in the striatum primarily contributes to PD pathology.
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Dopaminergic neurons correspond to approximately 3-5% of total neurons in the substantia nigra.
Dopaminergic neurons play a significant role in the cardiovascular, renal, hormonal, and central nervous systems.
Dopaminergic neurons are thought to control processes as diverse as movement and drug addiction.
An excessive amount of dopamine in the brain is affiliated with schizophrenia characterized by altered behavior and delusions.
Dopamine deficiency in the substantia nigra in aged populations results in PD which constitutes a major public health burden in westernized countries where the average life expectancy is 85 years or greater.
Hegarty, S. V.; et al. Midbrain dopaminergic neurons: a review of the molecular circuitry that regulates their development. Dev Biol. 2013, 379(2): 123-38.