Neuronal Regeneration

Neuronal regeneration is a high energy demanding process however, with maturation, axonal mitochondria transport progressively declines. Mitochondria are cellular powerhouses that supply ATP; essential for neuron growth, survival, and regeneration. Motile mitochondria can become stationary and in mature axons of the central nervous system (CNS), the majority of the mitochondria become stationary with only about 20-30% remaining motile. With this reduction in mitochondrial transport, mature CNS axons fail to regrow after injury, resulting in neurological impairment. Previous studies suggest that mature CNS neurons have lost their growth capacity and to recover from an injury, neurons need to quickly reform an active growth cone where damaged …show more content…
So far we know that an increase of SNPH decreases the amount of motile mitochondria and we also know that as neurons mature the expression of SNPH increases but, can mitochondrial transport be regulated so that mature neurons will regain growth capacity? Well it turns out it can be. Axonal mitochondrial motility in cortical neurons was manipulated by co-expressing SNPH with Mirol (an SNPH loss-of-function mutant) via lentivirus. Although neurons co-expressing SNPH show some axon growth, the expression of Mirol alongside SNPH increased axonal growth capacity. It was also concluded that suppressed growth (as a result of overexpressed SNPH) can be recovered by supplying 200 µM of ATP through electroporation, suggesting that supplying ATP also contributes to axon growth and enhancing mitochondrial transport in injured mature …show more content…
Axonal injury allows for mitochondrial depolarization and depolarized mitochondria supply lower levels of ATP that will trigger axon degeneration. If the damaged mitochondria are replaced it will slow down degeneration of the axon as well as support axonal recovery in mature neurons. ATP maintenance was measured in wildtype and SNPH KO neurons 6 hours after axotomy. Enhancing mitochondrial transport in SNPH KO neurons recover energy deficits at three and five hours after injury, while wildtype neurons do not show a change in recovery. However, in wildtype (control) neurons, if Mirol is expressed that will also recover energy deficits. It is important to remember that although a decrease in SNPH allows for an increase in motile axonal mitochondria, so does the expression of Mirol in a wildtype neuron because Mirol, in a mature neuron stops the expression of SNPH. Mitochondrial transport is essential in maintaining ATP supply and preventing deficits when axonal damage