Prozac leads to neurogenesis of neural progenitors

Fluoxetine targets early progenitor cells in the adult brain — Encinas et al. 103 (21): 8233 — Proceedings of the National Academy of Sciences

One of the first mechanistic attempt at explaining the effects of SSRIs. But how do new progenitors affect depression? Maybe this is an epiphenomenon. Maybe not.

TR: Future of Neurotechnology

Technology Review: Emerging Technologies and their Impact

I don’t know too much about Zach Lynch, other than that he has a blog and refers to his company as the “neurotechnology market authority”, but there are some interesting tidbits from the TR interview:

TR: Research suggests that antidepressants are effective partly because they stimulate neurogenesis. So companies such as BrainCells, based in San Diego, CA, are screening compounds that promote growth of neural stem cells in the brain. They say these drugs could bring new therapies for depression and, eventually, neurodegenerative diseases.

ZL: It’s an exciting area, and the investment community is certainly interested. But the jury is still out.

TR: We’re also starting to see a new kind of therapy for brain-related illnesses — electrical stimulation. Various types of stimulation devices are now on the market to treat epilepsy, depression, and Parkinson’s disease. What are some of the near- and far-term technologies we’ll see with this kind of device?

ZL: We’re seeing explosive growth in this area because scientists are overcoming many of the hurdles in this area. One example is longer battery life, so devices don’t have to be surgically implanted every five years. Researchers are also developing much smaller devices. Advanced Bionics, for example, has a next-generation stimulator in trials for migraines.

In the neurodevice space, the obesity market is coming on strong. Several companies are working on this, including Medtronics and Leptos Biomedical. In obesity, even a small benefit is a breakthrough, because gastric bypass surgery [one of the most common treatments for morbid obesity] is so invasive.

In the next 10 years, I think we’ll start to see a combination of technologies, like maybe a brain stimulator that releases L-dopa [a treatment for Parkinson’s disease]. Whether that’s viable is a whole other question, but that possibility is there because of the microelectronics revolution.

The real breakthrough will come from work on new electrodes. This will transform neurostimulator applications. With these technologies, you can create noninvasive devices and target very specific parts of the brain. It’s like going from a Model T to a Ferrari. Those technologies will present the real competition for drugs.

Social isolation delays the positive effects of running on adult neurogenesis

Social isolation delays the positive effects of running on adult neurogenesis – Nature Neuroscience

From the Apr 9, Nature Neurosci:

Social isolation delays the positive effects of running on adult neurogenesis
Alexis M Stranahan, David Khalil & Elizabeth Gould

Social isolation can exacerbate the negative consequences of stress and increase the risk of developing psychopathology. However, the influence of living alone on experiences generally considered to be beneficial to the brain, such as physical exercise, remains unknown. We report here that individual housing precludes the positive influence of short-term running on adult neurogenesis in the hippocampus of rats and, in the presence of additional stress, suppresses the generation of new neurons. Individual housing also influenced corticosterone levels—runners in both housing conditions had elevated corticosterone during the active phase, but individually housed runners had higher levels of this hormone in response to stress. Moreover, lowering corticosterone levels converted the influence of short-term running on neurogenesis in individually housed rats from negative to positive. These results suggest that, in the absence of social interaction, a normally beneficial experience can exert a potentially deleterious influence on the brain.

New Neurons Migrate in Adults

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.


Recipe: ES cells to pure NS cells

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].

Impressive spinal cord regeneration with neural stem cells

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.

Self-replacing network in hippocampus

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.