Research Notes

Fly Model of Parkinson's Disease With genome projects finishing at an ever quickening pace, many new animal models of human disease are being developed. A very promising one is a Drosophila version of Parkinson's disease (M.B. Feany and W.B. Bender, "A Drosophila model of Parkinson's disease," Nature, 404:394-8, March 23, 2000). At Harvard Medical School, Mel Feany, an instructor in pathology, and Welcome Bender, a professor of biological chemistry and molecular pharmacology, created flies transgenic for the human gene encoding alpha synuclein. The flies show the dense brain inclusions called Lewy bodies characteristic of the human diseased brain, the telltale depletion of dopaminergic neurons, and motor symptoms--they cannot climb the walls of their vials, as flies tend to do. As in humans, the impairment begins gradually in midlife and worsens with age. Lifespan appears normal, if the animals are properly cared for. "These flies sit down on their food, where the next generation of larvae can chew on their toenails. But if we transfer them to fresh vials, their lifespan is not dramatically different," observes Bender. Long-term applications of the Parkinson's fly are clinically oriented. "It will be wonderful for drug testing, because the flies are small, cheap, easy to feed, and don't live very long. It will also be great to test potential environmental factors," says Feany. In the meantime, the researchers and colleagues at Harvard specializing in neurodegenerative diseases are focusing on using the model to identify other genes implicated in this complex disorder. "A promising research avenue is to look for enhancers and suppressors, getting a handle on other genes that might affect the loss of dopaminergic cells," says Bender. And that, too, should translate from fly to human. "It's likely that Parkinson's disease in people results from small genetic changes in many genes that influence the onset and progression of symptoms," adds Feany. --Ricki Lewis In Vitro Female Genital Tract Reveals HIV in Action Researchers have watched HIV traverse single layers of immortalized cells, but this hardly mimics the multilayered, complex cellular architecture of the human female genital tract. A team from the University of Pittsburgh and Northwestern University has developed a much more realistic stand-in (K.B. Collins et al., "Development of a novel in vitro organ culture model to study HIV-1 transmission in the female genital tract," Nature Medicine, 6[4]:475-9, April 2000). The cell source: 30 healthy women undergoing hysterectomies. From each piece of donated tissue, the researchers cultured six to eight models, which include not only the epithelial layers, but also the various immune system cells that might be points of entry for the virus. "The beauty of the in vitro model is that there are a lot of questions that so far you can only ask after the event in humans. And of course we wouldn't want to do this with women. The in vitro model provides controlled conditions under which we can monitor the infective process," says Phalguni Gupta, a professor in the department of infectious diseases and microbiology in the graduate school of public health at the University of Pittsburgh. HIV is applied to the tissue and is assayed by the number of HeLa cells it turns blue by activating a beta galactosidase marker. Already the researchers have shown that HIV preferentially infects T cells and some macrophages, sparing Langerhans and dendritic cells. Ongoing experiments will identify the very first cell type that is infected. "We will use the system to understand in which stages of the menstrual cycle a woman is most susceptible to HIV infection. We can add hormones that change during the cycle," Gupta adds. Farther down the road, the model will be useful in testing topical treatments to block HIV transmission in the reproductive tract. An anal-route model based on rectal tissue is in the works too.--Ricki Lewis Nicotine and Parkinson's Nicotine improves the condition of patients with Parkinson's disease, according to a study in press in Behavior and Cognition. Paul Newhouse, director of the clinical neuroscience research unit at the University of Vermont, and his colleagues found that nicotine released into the bloodstream over two weeks via the nicotine patch, used in smoking cessation, improved the patients' performance on attention, learning, and reaction time tasks. The death of cells that release the neurotransmitter dopamine in the brain is the cause of the tremors and similar symptoms in Parkinson's disease. Patients received 14 mg of nicotine over the two weeks. The improvement continued after the nicotine was stopped, though some of the 15 patients in the study did show declines in tests given two weeks after the patches were removed. The pilot research is consistent with the hypothesis that nicotine triggers the release of dopamine in the brain. "Whether nicotine can prolong that process has never been studied. We haven't administered it anywhere near long enough to establish that," he says. The research was not a placebo-controlled, double-blind study, and such a study should be done in the future, notes Newhouse.--Harvey Black

Research Notes

Interested in reading more?

Become a Member of