We’ve heard in the past about neurogenesis in adults, but as far as we understand, this only happens in limited locations throughout the brain. However, what if those new neurons migrate to different places?
New evidence in mice suggests that after being born, new neurons can travel along the flow of spinal fluid to end up in the olfactory bulb.
If there is migration to other locations in the brain, the ramifications for computational models of brain systems are significant.
In the August PLoS Biology, there is an article showing the production of pure neural stem cells from human embryonic stem cells.
The procedure is quite simple: Add growth factors FGF-2 and EGF to the ES cells and you get pure NS cells, which overcomes several of the limitations of previous neurosphere-based assays [Nature Methods].
Human neural stem cells differentiate and promote locomotor recovery in spinal cord-injured mice — PNAS
This article has some very promising results. I haven’t read the paper in detail, but here’s the executive summary. Human neural stem cells (hNSCs) were injected into mice that received a precision contusion (laminectomy) injury at spinal level T9. Control groups had vehicle and human fibroblast cell injections after receiving the same injury.
The group receiving hNSCs showed a significant functional recovery from the vehicle group. The fibroblast group did not. Then, to prove that the functional recovery was due to the new neurons and glia from the hNSC, the investigators injected the recovered mice with diptheria toxin, which affects human neurons while essentially leaving mouse neurons alone. After the toxin injection, the recovered mice with hNSC regressed back to the same behavioral performance as the vehicle group. That is, the functional recovery reversed after selective de-activation of the hNSC-derived neurons.
Additionally, the hNSCs produced both neurons and oligodendrocytes (myelin producers) in the mice. Through EM, it was verified the hNSC-derived neurons formed synapses with endogenous mouse neurons.
Amazing. Work like this shows how genetically similar mouse and human neurons (well, at least spinal cord neurons) must be. And, with regard to the race to understand and control stem cell development, this provides further evidence of how strongly the local environment can influence differentiation.
Some recent work in Neuron (full article; easy to read summary) shows how hippocampal neurons can cause neural progenitor cells to produce new neurons in the hippocampus. I find this fascinating since the network literally is replacing itself through its own dynamics.
The mechanism seems to be that GABAergic cells synapse onto progenitor cells and cause calcium entry due to the depolarization. (GABAergic synapses are often excitatory in young cells which have elevated intracellular chloride levels.) The increased calcium entry leads then to activation of genes coding for neuronal differentiation-related proteins.
Also, here’s some earlier work from Malenka’s lab along the same lines.
The NYT has a nice summary of a recent Cell paper, where investigators from the Karolinska Institute used a wonderfully innovative technique to determine the age of many cells, including neurons from visual cortex and the cerebellum.
The general idea is this: Up until 1963, above ground nuclear weapons testing was allowed, dispersing radioactive carbon (14C) into the atmosphere. This “tagged” carbon was integrated into all plants and animals at that time and, since 1963, at an exponentially decreasing amount. Thus, calibrated with pine tree trunk rings (which are produced every year), the scientists are able to judge the age of cells by seeing how much of the genomic DNA of the cell contains 14C. Genomic DNA is created during cell division and, as the authors show, it appears not to be regenerated since preserved cell specimens from different years show the characteristic exponential decay of 14C post-1963.
The neat finding is that several neurons, from cortex and cerebellum, are very old… in 50-60 year old cadavers, neurons were found that were just as old or nearly just as old as the cadavers. So, even if there is neurogenesis occuring, it is now almost certain that some of our neurons are with us throughout life.
Looks like spinal cord regeneration might be the first target for embryonic stem cell therapy trials in humans. More info in the Science article.
It looks like Geron has developed a protocol to reliably induce ES cells to become oligodendrocytes, the glial cells that produce the myelin sheath. Here’s the details from the article:
For newly injured rats, the results are promising. In animals that received oligodendrocyte precursors 7 days after their injury, the cells survived and apparently helped repair the spinal cord’s myelin. Within 2 weeks, treated rats scored significantly better on standardized movement tests than control animals, which had received human fibroblasts or a cell-free injection.
No, we haven’t fallen off the face of the earth… just busy. (well, I can’t speak for Bayle)
Interesting news in the AOP section of Nature Medicine. Looks like a combined therapy of cAMP and schwann cells can aid in spinal cord regeneration. This study shows that inhibition of cyclic AMP signaling is a major problem in axon regeneration. (Definitely some connections here with the MM Poo work on growth cone turning in response to cAMP from a pipette.)
Read on for the abstract….