Restorative neuroscience, the study to identify means to replace damaged neurons and recover permanently lost mental or physical abilities, is a rapidly advancing scientific field considering our progressively aging society. Redirecting immature neurons that reside in specific brain areas towards the sites of brain damage is an appealing strategy for the therapy of acute brain injury or stroke.
The adult brain has limited capacity of self-repair
In the aging 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 world-wide. Nerve cells are particularly sensitive to microenvironmental insults and their loss clearly manifests as neurological deficit. Since the innate ability of the adult human brain to regenerate is very poor and confined to its few specialized regions, 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 thus offers frontline opportunities to design potent therapeutic interventions.
Neurons drive neurons: a new concept integrating brain activity with repair
Only two regions of the postnatal mammalian brain are known to retain their intrinsic potential to allow the generation of new neurons throughout life: the olfactory system decoding smell and the hippocampus acting as a key hub for memory encoding and storage. In humans, the generation of new neurons in the olfactory system rapidly ceases during early childhood. "Which are the processes that disallow this innate regenerative process in the human brain and how can dormant progenitors be reinstated to produce new neurons and guide those towards brain areas that require repair?" is a central yet unresolved question for brain repair strategies.
Opportunities for restorative neuroscience
Tibor Harkany, Professor of Molecular Neurosciences at the Medical University of Vienna goes one step further "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".
Brain activity defines therapeutic success?
The realization 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 a new and exciting opportunity for regenerative neuroscience" adds Tomas Hökfelt, Guest Professor at the Center for Brain Research.
Provided by: Medical University of Vienna