01 Jul 2001

Most research trying to coax adult central nervous system neurons into repairing nerve injury focuses on the environment through which regenerating neurons have to extend new growth cones and axons. A study published today in the Journal of Neuroscience approaches this problem differently, by trying to overcome the adult neurons' intrinsic growth limitations.

Maureen Condic of the University of Utah School of Medicine in Salt Lake City, Utah, reports that a single genetic manipulation restores the ability of adult sensory neurons to grow as well as do early postnatal neurons, which regenerate much more readily than their older counterparts. All experiments were in cell culture.

Condic infected dorsal root ganglion neurons from adult rats with adenovirus carrying human integrin genes to create transgenic neurons that express these integrins at levels seen in embryonic and early postnatal cells.

Integrins are a family of extracellular matrix (ECM) receptors that serve a mechanical function in migratory cells by adhering to ECM proteins such as laminin or fibronectin and helping pull the neuron's leading edge forward. Though integrin expression is downregulated in most of the adult brain, it remains high in the dentate gyrus of the hippocampus and the rostromigratory stream, two brain areas known to produce new, and presumably migratory, neuronal progenitors in the adult, says Condic.

When Condic cultured the neurons on different substrates-one strongly growth-promoting, one weakly promoting, and one containing inhibitory proteoglycans seen in glial scars-she found that the adult neurons expressing high integrin levels grew as well as did the early postnatal ones. Moreover, the adult transgenic neurons regained the ability to adapt to different environments by regulating integrin expression, a mechanism embryonic neurons use to compensate for poor growth-promoting and inhibitory conditions, writes Condic.

"We saw pronounced improvement, easily more robust than achieved by any manipulation of the neuronal environment to date," said Condic.

Ron Cohen, CEO of Acorda Pharmaceuticals in Westchester County, New York, a biotech company working to develop therapies for spinal cord injury, calls the study "very interesting." He adds, however, that its usefulness for therapy development will remain unclear until the integrin effect has been repeated in other types of CNS neurons. Next, it needs to hold up in animal models, where regenerating neurons encounter other obstacles besides scar-associated proteoglycans, including white matter inhibitors such as Nogo (Abstract; Abstract ).—Gabrielle Strobel

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