Evidence of neuroprotective effect of transcription factor BCL11A

Neurons that produce the transcription factor BCL11A are shown in green. Credit: Marianna Tolve

The neurotransmitter dopamine affects the activity of various brain regions. Deficiency of this substance can have dramatic consequences: the death of dopaminergic neurons in the substantia nigra (a particularly sensitive part of the brain) is the cause of the central symptom of Parkinson’s disease. An international team at the University of Bonn is currently investigating the role of the transcription factor BCL11A in mouse and human cells. If this important element is missing, neurons become more sensitive and more likely to die. Researchers suspect that BCL11A may play a role in protecting neurons. Research is currently Cell report..

In the human midbrain Nerve cell Produces dopamine (dopaminergic neurons). “This neurotransmitter affects other neurons by amplifying or attenuating the activity of them,” explains Dr. Sandra Breath of the Institute for Reconstructive Neurobiology at the University of Bonn Hospital. Like radio treble and bass controls, these special neurons do not change songs or songs, but can significantly change their effects.Dopamine-producing neurons also play a major role in Parkinson’s disease: dopamine cell It is located in the substantia nigra, the dark-looking structure of the midbrain, and dies. The resulting lack of dopamine causes disease-related motor dysfunction.

Dopaminergic neurons form extensive connections in many brain regions, including the cerebral cortex and striatum. “This raises the question of whether there are specialized groups within these dopaminergic neurons that affect only specific areas of the brain,” said Dr. Emmanouil Metzakopian of the British Institute for Dementia at the University of Cambridge. I will explain. Human cells For research. The transcription factor BCL11A is known to be important in determining cell properties. For example, the cerebral cortex and the immune system. For the first time, Professor Blaess’s team investigated the role of BCL11A in various properties of dopaminergic neurons.

Labeling with fluorescent molecules

Researchers analyzed both the brain and human cells of developing and mature mice to determine in which dopamine neurons the transcription factor BCL11A was turned on. Next, mouse BCL11A-producing neurons were labeled with fluorescent molecules and lit under a microscope.

“This allowed us to see in which adjacent brain regions the dilation of these dopaminergic neurons grew,” said Collaborative Research Center 1089, “Health and Disease Synaptic Micronetworks,” and interdisciplinary research areas. “Life and Health at the University of Bonn”. The areas in the brain that were contacted by BCL11A-positive dopaminergic neurons were not arbitrary. For example, the target region was a small part of this brain region, rather than the entire striatum, which is part of the complex motor control circuits of the cerebrum.

Substantia nigra, which is particularly susceptible to neurodegeneration

Researchers investigated the process of neurodegeneration in the substantia nigra using mice from the German Center for Neurodegenerative Diseases (DZNE), which lost dopamine-producing neurons as well as Parkinson’s disease. “In patients with Parkinson’s disease, substantia nigra dopaminergic neurons are known to die significantly more than other neurons. Brain region“Therefore, this area is considered to be particularly sensitive to neurodegeneration,” said Dr. Donato Di Monte, a professor at DZNE who was involved in this part of the study.

The team compared dopamine Neuron “Mice with Parkinson’s disease” with and without BCL11A.In Substantia nigra, This transcription factor is marked Dopaminergic neurons It was particularly susceptible to neurodegeneration. More dopamine cells died if researchers stopped producing BCL11A in these cells. “This suggests that BCL11A may have a neuroprotective function,” Professor Blaess summarizes his major findings. The molecular mechanism behind this needs to be investigated in more detail in future studies. It will also be investigated whether the findings can be transferred from mice to humans.

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For more information:
Sandra Blaess et al, the transcription factor BCL11A, defines different subsets of midbrain dopaminergic neurons. Cell report (2021). DOI: 10.1016 / j.celrep.2021.109697

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University of Bonn

Quote: Evidence of neuroprotective effect from transcription factor BCL11A (2021, September 14), https: // 9 2021 Obtained on the 14th of March

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Evidence of neuroprotective effect of transcription factor BCL11A

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