According to the Hungarian Academy of Sciences, collaborative efforts between the National Brain Research Program of Hungary/Semmelweis University in Budapest and the Center for Brain Research of the Medical University of Vienna has discovered new aspects of neuron function that could prove helpful in the fight against Parkinson’s, Alzheimer’s, and other neurological diseases.
The researchers’ efforts have revealed that some mature neurons are able to reconfigure their local microenvironment in such a way that it becomes conducive for adult-born immature neurons to extensively migrate.
In an ageing Western society, acute brain damage and chronic neurodegenerative conditions (e.g. Alzheimer’s and Parkinson’s diseases) are amongst the most debilitating diseases, affecting hundreds of millions of people worldwide. Nerve cells are particularly sensitive to microenvironmental insults, and their loss clearly manifests as a neurological deficit.
Since the innate ability of the adult human brain to regenerate is very poor and is confined to a few specialised regions of the brain, a key question in present-day neurobiology is how to establish efficient strategies that can replace lost neurons, guide competent cells to the sites of injury and facilitate their functional integration to regain lost functionality. “Cell replacement therapy” offers frontline opportunities for the design of potent therapeutic interventions.
The new Austro-Hungarian study goes well beyond the known frontiers of current neuron research through the discovery that the migration of new-born neurons requires resident, differentiated nerve cells to “clear their path” by digesting away some of the glue that fills the space between nerve cells.
This process is dependent on the activity of resident neurons, thus suggesting the integration of the ancient developmental process of active cell movement with the integrative capacity and activity patterns of the brain. “By realizing that differentiated neurons are critical operators in this process we finally lay our hands on an “on switch” which we can use to produce a molecular landing strip for migrating neuroblasts to home in on areas of critical need,” explained Alán Alpár, the study’s senior author.
Tibor Harkany, Professor of Molecular Neurosciences at the Medical University of Vienna went one step further, saying that:
“We mapped the entire molecular machinery used by differentiated neurons to make way for their migrating adult-born replacements. This clearly offers a pharmacological concept to reroute neurons in sufficient quantities for neurorepair once damage occurs. Even though distances can be considerably long, we are confident that molecular means exist to tackle these challenges.”
The realisation that differentiated neurons hold the key to directional cell migration is of enormous significance, since they are wired into the brain circuitry, receive information from not only adjacent but also far-away regions and are activated by these specific connections at precisely given times. Consequently, migration controlled by the newly described specific neuronal subset can be aligned with brain activity, or conversely, with inactivity as evoked by neuronal loss during brain diseases. “To identify the physiological stimuli and stressors which activate these guide-neurons will herald in a new and exciting opportunity for regenerative neuroscience,” adds Tomas Hökfelt, Guest Professor at the Center for Brain Research.
Via the Hungarian Academy of Sciences
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