neurodudes

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.

Study Finds Little Advantage in New Schizophrenia Drugs - New York Times

Looks like the current crop of schizophrenia drugs come up short.

The study, which looked at four new-generation drugs, called atypical antipsychotics, and one older drug, found that all five blunted the symptoms of schizophrenia, a disabling disorder that affects three million Americans. But almost three-quarters of the patients who participated stopped taking the drugs they were on because of discomfort or specific side effects.

NEUROSCIENCE: Preventing Alzheimer’s: A Lifelong Commitment? — Marx 309 (5736): 864 — Science

Some quotes of interest:

For example, a 1997 study of 642 elderly people, conducted by Denis Evans of Rush Presbyterian-St. Luke’s Medical Center in Chicago and his colleagues, found that each year of education reduces a person’s risk of Alzheimer’s disease by 17%.

[...]

As in other studies, Snowdon and his colleagues found that high education levels seem to protect against Alzheimer’s disease. The researchers originally thought that this supported the idea that more education leads to a higher cognitive reserve. But analysis of biographical essays the sisters had written when they entered the convent, usually in their early 20s, pointed in a different direction. The early writings, Snowdon says, were an even better predictor of who would get Alzheimer’s disease than education level. “Those who had the lowest linguistic skills at age 22 had a very high risk of Alzheimer’s,” Snowdon says. Indeed, most of the cases occurred in the nuns whose essays put them in the bottom third on the linguistic ability scale.

[...]

A few years ago, Arthur Kramer of the University of Illinois, Urbana-Champaign (UIUC), and his colleagues performed a meta-analysis of 18 trials involving adults between the ages of 55 and 80 that explored the effects of physical exercise on performance of various cognitive tasks. They concluded that the answer to the question, “Does aerobic exercise enhance cognition?” was an “unequivocal yes.”

[...]

As reported in the April issue of the American Journal of Epidemiology, study members who engaged in four or more physical activities, which could be anything from gardening to jogging or biking, had about half the risk of dementia as that of participants who engaged in one or none. The effect was primarily seen, however, in persons who did not carry a gene variant called ApoE4 that’s known to increase Alzheimer’s risk. In the ApoE4-endowed population at least, genetics seems to trump activity.

[...]

Another possibility is that exercise turns up production of proteins that stimulate neuronal growth. About 10 years ago, Carl Cotman’s team at UC Irvine, found that the brains of rats who ran voluntarily on a wheel show increases in one such factor, BDNF (for brain-derived neurotrophic factor). The increase was particularly strong in the hippocampus, an area involved in learning and memory that’s hard-hit by Alzheimer’s disease.

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.

The March issue of Nature Rev. Neuroscience includes an interesting article about an herbal remedy, ibogaine, which appears to upregulate glial-derived neurotrophic factor (GDNF) in the VTA (ventral tegmental area, which seems to play a key role in reward learning). Apparently, an increase in GDNF activity makes alcohol (and presumably other VTA-involved compounds, like opiates) less addictive.

A round up of a bunch of potential analgesics. Not computational or anything, but interesting if you’re into the neurobiology or treatment of pain.

http://nytimes.com/2005/02/15/health/15pain.html

Cyberonics produces a vagal nerve stimulator to help patients control epileptic seizures. Now, it looks like stimulating the vagus nerve might also help treat chronic depression. Interestingly, the economics are in favor of the device: According to a NYT article: The cost of the Cyberonics device and implanting it is about $20,000. Cyberonics said insurers had calculated that severe depressions that cannot be treated cost an average of $42,000 a year per patient, mostly from the injuries suffered in attempted suicides and accidents related to the illness.

In a Nature article from two weeks agp, Rothstein et al. demonstrate how standard, penicillin-like antibiotics are able to prevent excitotoxic glutamate damage by upregulating glutamate re-uptake transporters. They found the antibiotic treatment effective in animal models of ALS (Lou Gerig’s disease) and stroke-induced ischemic shock; of course, the potential (but yet unproven) benefits of this drug could be much greater — any excitotoxicity-related disease, including spinal cord injury, could be aided by increased glutamate clearance from the extracellular medium.

What’s even neater is how they did it: A blind screen of 1,000 already FDA-approved drugs. Very smart. This is a peek at the kind of power possible with automated assays, like the immunoblotting-densitometry combination used in this work.

A very good summary can be found in this week’s Science.

Amazing results. I hope this serves as a wake-up call to those who still haven’t realized the incredible advances that are being made possible through the use of embryonic stem cells. From the July 27, 2004 issue of PNAS:

Transplanted human fetal neural stem cells survive, migrate, and differentiate in ischemic rat cerebral cortex
S. Kelly, T. M. Bliss, A. K. Shah, G. H. Sun, M. Ma, W. C. Foo, J. Masel, M. A. Yenari, I. L. Weissman, N. Uchida, T. Palmer and G. K. Steinberg

Full article

We characterize the survival, migration, and differentiation of human neurospheres derived from CNS stem cells transplanted into the ischemic cortex of rats 7 days after distal middle cerebral artery occlusion. Transplanted neurospheres survived robustly in naive and ischemic brains 4 wk posttransplant. Survival was influenced by proximity of the graft to the stroke lesion and was negatively correlated with the number of IB4-positive inflammatory cells. Targeted migration of the human cells was seen in ischemic animals, with many human cells migrating long distances ({approx}1.2 mm) predominantly toward the lesion; in naive rats, cells migrated radially from the injection site in smaller number and over shorter distances (0.2 mm). The majority of migrating cells in ischemic rats had a neuronal phenotype. Migrating cells between the graft and the lesion expressed the neuroblast marker doublecortin, whereas human cells at the lesion border expressed the immature neuronal marker {beta}-tubulin, although a small percentage of cells at the lesion border also expressed glial fibrillary acid protein (GFAP). Thus, transplanted human CNS (hCNS)-derived neurospheres survived robustly in naive and ischemic brains, and the microenvironment influenced their migration and fate.

Neat article on how immersive VR treatment results in a significantly lower pain for severe burn victims during treatment. Click below to read the whole article.
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