BCL11A: Evidence for neuroprotective effect

Researchers at the University of Bonn investigate the role of the transcription factor for dopamine-producing neurons

The neurotransmitter dopamine influences the activity of a wide variety of brain areas. A deficiency of this substance can have drastic consequences: The death of dopamine-producing nerve cells in the substantia nigra – a particularly sensitive part of the brain – is what causes the core symptoms of Parkinson’s disease. An international team from the University of Bonn has now investigated the role played by the transcription factor BCL11A in mice and human cells. If this important factor is missing, the neurons are even more sensitive and more likely to die. The researchers suspect that BCL11A plays a protective role for neurons. The study is now published in Cell Reports.

The human midbrain contains nerve cells that produce dopamine (dopaminergic neurons). “This neurotransmitter influences other neurons by amplifying or dampening their activity,” explains Prof. Dr. Sandra Blaess from the Institute for Reconstructive Neurobiology at the University Hospital Bonn. Like the treble and bass controls on a radio, these special neurons do not change the song or the tune, but they can drastically alter the effect. Dopamine-producing neurons also play a major role in Parkinson’s disease: the dopamine cells located in the substantia nigra, a dark-appearing structure in the midbrain, die off. The resulting lack of dopamine causes the movement dysfunctions associated with the disease.

The dopamine-producing neurons form extensive connections in a large number of brain areas, for example in the cerebral cortex or the striatum. “This raises the question of whether there are specialized groups within these dopaminergic neurons that affect only certain areas of the brain,” Dr. Emmanouil Metzakopian of the UK Dementia Research Institute at The University of Cambridge explains, who contributed data on human cells to the study. The transcription factor BCL11A is known to be important for determining cell properties, for example in the cerebral cortex and also in the immune system. Prof. Blaess’ team now investigated for the first time what role BCL11A plays in the different properties of dopaminergic neurons. […]

Participating Core Facilities: The authors acknowledge the support from the Microscopy, and Virus Core Facilities.

Participating institutions and funding:
In addition to the Institute of Reconstructive Neurobiology, the Institute of Anatomy and the Department of Neuropathology of the University of Bonn, the German Center for Neurodegenerative Diseases (DZNE), the University of Ulm, the University of Cambridge, the UK Dementia Research Institute (UK DRI) at Cambridge and the University of Hong Kong are involved. The study was mainly funded by the German Research Foundation (DFG).

Publication: M. Tolve et al.: The transcription factor BCL11A defines distinct subsets of midbrain dopaminergic neurons, Cell Reports, DOI: https://doi.org/10.1016/j.celrep.2021.109697