Fish give clues to regeneration

Zebrafish are known for their capacity to regenerate numerous tissues, including the heart, spinal cord and appendages. A group of scientists led by Kenneth Poss of Duke University (Durham, NC) has begun to identify specific mechanisms of the zebrafish regeneration process. Their findings could contribute to research of tissue regeneration in humans.

The researchers focused on the caudal fin, which zebrafish can regenerate within two weeks of partial amputation. They investigated activity of micro-RNAs (miRNAs), which are small, noncoding RNAs that are known to have numerous roles in organogenesis and stem cell maintenance (Genes Dev. 22, 728–733; 2008). As the researchers suspected, many miRNAs showed sharp increases or decreases in expression during the fin regeneration process. One miRNA in particular (miR-133) seemed to act as a 'brake' on the proliferation of undifferentiated progenitor cells, as its expression was low while the fin was just beginning to regenerate but rose sharply as the fin approached completion. This miRNA may have a crucial role in preventing unwanted growth.

The scientists showed that antagonizing miR-133 triggered substantial changes to the shape and size of the fin. This suggests that manipulation of miRNAs may enable control over regenerative processes.

A mouse model for autism?

Though autism spectrum disorder (ASD) is highly prevalent, affecting 1 out of 150 births, little is known about the neural mechanisms of this complex condition. A group of scientists led by Timothy DeLorey (Molecular Research Institute, Palo Alto, CA) has developed a mouse model that may help illuminate the disorder (Behav. Brain Res. 187, 207–220; 2008).

The scientists examined mice that were engineered to lack the gene Gabrb3, which is part of a chromosomal cluster that has been implicated in ASD. In humans, ASD is characterized by impaired sociability, repetitive behavioral patterns and communication deficits. The team found that modified mice had similar behavioral characteristics. When placed near an unfamiliar mouse, knockout mice were significantly less likely to approach the stranger than were the 'sociable' wild-type mice and were less likely to prefer a novel mouse over a familiar one. The knockout mice also explored their cages less and showed more repetitive, stereotypical behavior. The scientists noted that the brain structure of modified mice bore similarities to that of humans with ASD.

Though more research is needed to establish the parallels between modified mice and humans with ASD, the mice seem to be a promising model for the disorder.

Alzheimer's vaccine tested in dogs

Alzheimer's disease is a form of dementia that affects more than 5 million people in the US. It is progressive and fatal and has no known cure. It is characterized by neuronal death, which may be linked to the formation of plaques of β-amyloid in the brain. Immunotherapy against β-amyloid has shown promise in reducing the formation of plaques in mice and is being pursued as a potential treatment in humans. Because dogs develop β-amyloid plaques and cognitive declines similar to those seen in humans with Alzheimer's, they may be a good model for testing new treatments.

Elizabeth Head and colleagues from the University of California (Irvine) immunized dogs with a β-amyloid vaccine for a period of roughly 2 years. The immunized dogs did not perform better on cognitive tests than did a control group of nonimmunized dogs, but their brains did have fewer plaques and lower levels of β-amyloid, particularly in the prefrontal cortex, a brain area associated with learning and memory (J. Neurosci. 28, 3555–3566; 2008).

These results suggest that targeting β-amyloid plaques may not effectively treat the symptoms of Alzheimer's disease. Immunotherapy may be more effective if it is administered before extensive plaques form or in combination with other treatments aimed at improving neuronal health.