Dopaminergic neurons of the midbrain are the main source of dopamine (DA) in the mammalian central nervous system.
Their loss is associated with one of the most prominent human neurological disorders, Parkinson’s disease (PD).
Dopaminergic neurons are found in a ‘harsh’ region of the brain, the substantia nigra pars compacta, which is DA-rich and contains both redox available neuromelanin and a high iron content.
Although their numbers are few, these dopaminergic neurons play an important role in the control of multiple brain functions including voluntary movement and a broad array of behavioral processes such as mood, reward, addiction, and stress.
Studies into the developmental pathways which are involved in the generation of dopaminergic neurons in the brain have led to the identification of several specific transcription factors including Nurr1, Lmx1b and Pitx3, all shown to be important in the development of the mesencephalic dopaminergic system.
The selective degeneration of these dopaminergic neurons in the substantia nigra pars compacta leads to PD but the exact cause for this nigral cell loss is still unknown.
Parkinson’s patients could be helped by fresh insights gained from studies of tiny tropical fish.
Research using zebrafish has revealed how key brain cells that are damaged in people with Parkinson’s disease can be regenerated.
The findings offer clues that could one day lead to treatments for the neurological condition, which causes movement problems and tremors.
Parkinson’s occurs when specialized nerve cells in the brain are destroyed.
These cells are responsible for producing an important chemical called dopamine.
When these cells die or become damaged, the loss of dopamine causes body movements to become impaired. Once these cells are lost from the human brain, they cannot be repaired or replaced.
In zebrafish, however, dopamine-producing nerve cells are constantly replaced by dedicated stem cells in the brain, the researchers found.
The team, led by the University of Edinburgh, found the immune system plays a key role in this process.
In some regions of a zebrafish’s brain, the process does not work, however.
Research using zebrafish has revealed how key brain cells that are damaged in people with Parkinson’s disease can be regenerated.
In this microscope picture of a zebrafish brain, dopamine-producing nerve cells are shown in red and the stem cells that produce them are shown in green.
The image is credited to Thomas Becker, The University of Edinburgh.
Researchers say understanding the immune signals that facilitate the replacement of these nerve cells could hold vital clues to developing treatments for people.
The study, published in the Journal of Neuroscience, was funded by the Biotechnology and Biological Sciences Research Council and the Medical Research Council.
Dr. Thomas Becker, of the University of Edinburgh’s Centre for Discovery Brain Sciences, said:
“We were excited to find that zebrafish have a much higher regenerative capacity for dopamine neurons than humans.
Understanding the signals that underpin regeneration of these nerve cells could be important for identifying future treatments for Parkinson’s disease.”
Source:
University of Edinburgh
Media Contacts:
Jen Middleton – University of Edinburgh
Image Source:
The image is credited to Thomas Becker, The University of Edinburgh.
Original Research: Closed access
“Regeneration of dopaminergic neurons in adult zebrafish depends on immune system activation and differs for distinct populations”
Lindsey J. Caldwell, Nick O. Davies, Leonardo Cavone, Karolina S. Mysiak, Svetlana A. Semenova, Pertti Panula, J. Douglas Armstrong, Catherina G. Becker and Thomas Becker. Journal of Neuroscience4 April 2019, 2706-18 doi:10.1523/JNEUROSCI.2706-18.2019
