Why is it so difficult to recover from brain injuries and diseases? Despite the various impressive abilities of the adult mammalian brain, it is unable to replace neurons lost to brain injuries and diseases.
One way of addressing this issue is to transplant neurons to replace the lost neurons, yet successful integration is required for these transplanted neurons to work effectively with existing neurons to process information and effect response.
Susanne Falkner, Sofia Grade, and their colleagues were able to demonstrate successful integration by transplanting late embryonic cortical neurons into affected regions of the primary visual cortex in mice.
Four weeks after transplantation, most of the new neurons Falkner and Grade observed had developed the expected morphologies. In response to secreted chemical cues, proper branching and projections to the correct target areas were exhibited by the new neurons. The transplanted neurons were also able to receive input from different parts of the brain with a connectivity ratio similar to that of existing neurons. On a larger scale, these neurons topographically organized inputs from the dorsal lateral geniculate nucleus (dLGN), which is necessary for proper neural circuit function.
After looking at the morphological features of these new neurons, Falkner and Grade looked at how selective the new neurons’ responses are to stimulus by observing the orientation and movement direction of these new neurons, because this would provide better evidence that the new neurons have successfully integrated. Falkner and Grade presented visual inputs to the mice’s contralateral eye to observe the neurons’ visual processing ability. They saw that this ability developed over time as the orientation and movement direction of the new neurons become increasingly accurate so that the new neurons’ ability to process visual inputs was eventually equal to the ability of existing neurons. After making careful observations of all the different properties expected of the new neurons, Falkner and Grade found sufficient evidence that the new neurons are fully integrated after 2-3 months and have “functional properties that are indistinguishable from their original counterparts.”
The research conducted by Kathrin Hemmer from the University of Luxembourg and her colleagues provides further evidence that transplanted neurons can be successfully integrated into the adult mouse brain. Like Falkner and Grade, Hemmer and her colleagues also transplanted new neurons into adult mouse brains, but Hemmer and her colleagues worked with induced neural stem cells (iNSCs) because they were interested in regenerative therapies. They chose to transplant the iNSCs in the cortex and the hilus of the dentate gyrus, an integral part of the hippocampal formation.
Hemmer and her colleagues observed that the iNSC-derived neurons developed morphologies and orientations similar to that of existing neurons. These iNSC-derived neurons also developed mature dendritic spines, which provides evidence that there is the formation of synaptic connections needed for these neurons to successfully integrate.
Both studies have shown that new neurons can successfully integrate into the adult mouse brain, and this provides hope that new neurons can also be successfully integrated into the adult human brain. This has vast implications for treating brain injuries and diseases because transplanted neurons can help replace the lost neurons, not only by physically taking up the space previously occupied by the lost neurons, but also by carrying out the functions of the lost neurons since they can be fully integrated. Hemmer’s research also shows the possibility of using iNSCs to replace the lost neurons as part of regenerative therapy. Using iNSCs is more advantageous than simply transplanting new neurons because iNSCs can differentiate into all the different types of neurons needed in the brain. Knowing that its lost neurons can be replaced, the brain of the individual suffering from a brain injury or disease will be slightly more at ease.