Reviewing Adult Neurogenesis in the Mammalian Brain

Whether and how specific portions of the adult brain produce new neurons and integrate them into functional neural circuits, a process known as neurogenesis, is of great importance to the future of regenerative medicine for the brain. It is probably easier to beneficially adjust the operation of existing tissue maintenance mechanisms than to safely deliver cells to a tissue that has no such capacity for regeneration. In the brain in particular, fine structure is enormously important to function, so comparatively blunt approaches to the delivery of replacement cells may prove challenging to implement safely.

In mammals, neural stem cells (NSCs) in the early embryonic period are called neuroepithelial cells. In the adult brain, most NSCs are quiescent. However, NSCs in the ventricular-subventricular zone (V-SVZ) and subgranular zone (SGZ) of the hippocampal dentate gyrus (DG) slowly divide to generate transit amplifying progenitor cells (TAPs) via a state called activated neural stem cells (aNSC) and thus generate new neurons. Such adult neurogenesis in the mammalian brain was first suggested in the 1960s, and neurogenesis has been found to occur primarily in the V-SVZ and SGZ throughout life. New neurons generated in these two neurogenic areas are incorporated into neural circuits and play important roles.

The attenuation of adult neurogenesis in the V-SVZ has been reported to cause abnormal olfactory and sexual behavior in mice. In addition, new neurons generated in the SGZ are also integrated into DG neural circuits and play an important role in the formation of short-term memory. The attenuation of neurogenesis in the mouse SGZ has been reported to result in the impairment of new memory formation. These new neurons are also important for the formation of spatial memories. Furthermore, new integrated neurons in the DG have the function of organizing past memories and alleviating the stress response. However, adult neurogenesis decreases with age, mainly due to a decrease in NSCs and TAPs. Several studies have reported that this reduction is likely to be caused by decreases in extrinsic signals that support the proliferation of NSCs, including mitotic signals such as EGF and FGF-2, and increases in systemic pro-aging factors.

Since the existence of adult NSCs and adult neurogenesis was confirmed, studies on adult neurogenesis have been intensively conducted with the expectation of applying NSCs and neurogenesis for regenerative medicine. Although the mobilization of endogenous NSCs has been studied as one of regenerative approaches to restore lost brain function in cerebrovascular diseases, traumatic brain injuries, neurodegenerative diseases, etc., there are still many issues to be solved, such as the depletion of NSCs and the directed migration of new neurons. From a fundamental point of view, identifying the regulatory mechanisms of adult neurogenesis and its age-related decline will undoubtedly lead to future regenerative medicine strategies.



any prospects for changing the brain's ability to do this

Posted by: J at July 7th, 2020 11:13 AM

brains are a complicated matter. New neurons or even synapses at the wrong place will wreak havoc. All other tissues and organs in the body can in theory be replaced with printed/grown parts. But since the brain also holds the information it cannot simply be repaired by putting a functional yet blank module. Some parts are more-or-less standard and could be replaced without killing the person (like hypothalamus, and some visual/ motor regions) yet still can alter the personality in subtle ways.

Having said that, i will go too far in the thought experiments. if you can increase neuro-generation 10x times in a couple of years you might end with a completely different person that might share most of the original memories. For example, you do this treatment to a victim of Alzheimer's Disease after their brain has been ravaged. You will end up with quite a different person, especially if core memories are lost. That would raise interesting legal questions in case of old crimes and such... Or let's say you have the prospect of AD and a treatment that has to kill 10% of your neurons and replace them with new ones. In a way , you as person, have to die to get the cure. Will you do it?

Posted by: cuberat at July 8th, 2020 9:58 AM
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