AT THE EDGE: HOPKINS RESEARCHERS REPORT FROM THIS MONTH'S SOCIETY FOR NEUROSCIENCES ANNUAL MEETING
The following tip sheet reports works-in-progress on the newest approaches to Alzheimer's disease, epilepsy, stem cell therapy and seasonality from Hopkins' neuroscientists attending this month's meeting in New Orleans, November 4 to 9.
Please observe embargoes heading each news tip. Nov.
To pursue any of these stories call Marjorie Centofanti at 410-693-2550 through Nov. 8, then 410-955-8725 thereafter.
SIBERIAN NIGHTS AND SNIFFLES: STUDY SUGGESTS A LINKEmbargoed until Tuesday, Nov. 7 at 8 a.m. EST
You're shutting down your mountain cabin for the winter: you lower the water heater and furnace thermostat, insulate where possible. Scientists have long suspected such changes go on in people at winter's approach: sex drive drops, metabolism slows, and also, to conserve energy, the immune system may operate at less than peak efficiency.
Now Hopkins researchers are shedding light on how the body "turns down" the immune system as daylight shortens. Using Siberian hamsters as a model -- the animals respond quickly to reduced daylight -- neuroscientist Randy Nelson, Ph.D., and doctoral candidate Deborah Drazen, with Georgia State scientist Greg Demas, have mapped neural pathways connecting the brain and sympathetic nervous system with the spleen -- one of the body's major immune organs.
They've also shown that a hamster's sympathetic nervous system behaves differently when day length is short, secreting higher amounts of the nerve transmitter norepinephrine to the spleen. Challenged with a "foreign" protein, short-day hamsters mounted a far weaker immune response than animals kept in long-day lighting.
"Studies show people are far more likely to catch a bacterial or viral illness in the winter," says Drazen, "but a variety of triggers other than shorter day length could be at work. Yet given that people's immune systems aren't terribly different from hamsters, this link between light and lowered immunity is one we should investigate further."
This study will be presented at a poster session on Tuesday, Nov. 7 at 8 a.m. number II-11, Hall G-J, Morial Convention Center
HOPKINS STUDY MAY LINK MOLECULAR GLITCH WITH EPILEPSY Embargoed until Sunday, Nov. 5 at 1 p.m., EST
Epilepsy is a complicated disease: Trying to find what sends areas of the brain into apparently spontaneous waves of firing keeps thousands at work in pharmaceutical companies around the world. Some scientists focus on cells' producing too much of a stimulatory nerve transmitter. Others say seizures come when something goes awry with the release of an opposing nerve transmitter called GABA (for gamma amino butyric acid) that normally damps down excitable nerve cells.
But Hopkins researcher Jehuda Sepkuty, Ph.D., offers evidence of still another possible glitch: something may lessen the steady supply of molecules a nerve cell uses to synthesize GABA. The less GABA to quiet target nerve cells, the greater the likelihood of target cells becoming excitable -- like taking a restraining hand off a feisty 4-year-old.
Sepkuty suspects the source of the problem is a molecule called EAAC1, which ferries GABA's molecular building blocks into key nerve cells. Once inside the cell, precursor molecules become part of the inhibitory neurotransmitter GABA.
In the study he's presenting, Sepkuty studied rats genetically engineered to produce less EAAC1. The rats exhibited episodes of staring and seizures. They also had hyperexcitable limbic systems in the brain -- all characteristics of epilepsy. The rats' cells also produced less GABA than normal. "We know this is rat epilepsy we're seeing. We're not sure if this the human version, though all the signs appear the same -- that's our next investigation," says Sepkuty. "But because this is a completely new approach to what may go awry in some epilepsy patients, it offers us novel sites for drug therapy," adds co-researcher Jeffrey Rothstein, M.D., Ph.D.
Session no. 150.3. The session title: "Uptake and transporters: amino acids." The poster will be displayed on Sunday, 11/5/00, from 1 pm. Presentation time is 3 p.m. Board no. 11-68 location: Morial Convention Center: Hall G-J
TWO STUDIES REFLECT REVOLUTION IN ALZHEIMER'S RESEARCHScientists Confirm Immune Approach
Embargoed until Sunday, Nov. 5 at 1 p.m., EST
Some Alzheimer's disease researchers have recently shifted their focus away from a search for genes (and gene therapy) to a more immediate approach: trying to prevent or reverse the destruction of nerve cells in the brain.
One novel technique enlists help from the immune system. Last year, researchers from a biotech company immunized lab animals against their own beta amyloid, a protein strongly implicated in AD. The animals -- mouse models of AD carrying human genes -- failed to form the characteristic plaques that dot patients' brain tissues.
Now Hopkins pathologists Juan Troncoso, M.D., David Borchelt, Ph.D., and Anne Vehmas, Ph.D., have confirmed this work, which they describe as "landmark," using a slightly different mouse model. The Hopkins mouse overproduces beta amyloid by a different route. "It's a first step, we think, to seeing how important beta amyloid is to the disease process," says Troncoso. "If it's as key a molecule as we suspect in triggering the disease, then immunizing against it could be a valuable approach to treat or prevent Alzheimer's.
Press conference on AD is at 4 p.m. on Sunday, in room 276 of the New Orleans Convention Center.
Poster on A-beta immunization #11781 Session 181.17 board Number OO-80, Sunday 11/5/00, at 1 p.m., Hall G-H, Morial Convention Center
MICROGLIA -- TELL-TALE SIGN OF IMPENDING DEMENTIA?Embargoed until Sunday, Nov. 5 at 1 p.m., EST
Another aspect of a subtle shift in AD research is an increasing spotlight on inflammation in key parts of the brain. "Many of us believe that the major damage of AD stems from inflammation -- the over-activation of the immune system -- and that damage begins long before symptoms surface," says neuroscientist Juan Troncoso, M.D. Recent work by Troncoso and his colleagues compared autopsied brains of normal people of all ages with those of elderly patients either suspected or confirmed to have the disease.
"Our study shows an over-abundance of specific immune cells, the microglia, in the brains of Alzheimer's patients, as well an increase in people with early signs of AD who are still functioning," says Anne Vehmas, Ph.D., a co-researcher. Those who lack symptoms have few microglia in the brain, compared with these other groups, she says.
Not only does this give surer signs that AD and immune damage are linked, the researchers say, but monitoring the cells' buildup could one day tell who's at risk -- an aspect of AD that's long-frustrated scientists and physicians.
Press conference on AD is at 4 PM on Sunday, room 276 of the New Orleans Convention Center.
Poster on microglia #10816 Session 576.1 Board Number PP-82, Tue. 11/7/00 at 1PM
ESTROGEN: AS HELPFUL FOR ALZHEIMER'S PATIENTS AS MENOPAUSAL WOMEN?Embargoed until Thursday, Nov. 9 at 8 a.m., EST
Thousands of postmenopausal women on estrogen can testify that the hormone has some effect on thinking, but the finer points of how the hormone acts and where it works in the brain are still a black box.
In a new study, Hopkins neuropathologist Vassilis Koliatsos, M.D., and a research team have found that estrogen can act directly on areas of the brain associated with memory -- some of the same areas targeted by Alzheimer's disease -- to turn on genes that maintain the nerve cells and enhance their functioning.
The scientists focused on specific neurons in the basal forebrain, "a part of the brain important for memory of events and facts," Koliatsos says.
Their study compared gene activity of "regular" rats with those whose ovaries had been removed to simulate menopause and with mice treated with estrogen. Nerve cells in rats with typical estrogen levels had genes turned on that let them respond to neuron-sustaining growth factors. Also "on" were genes that stimulate creation of the nerve transmitter acetylcholine. Most of the nerve cells linked with memory depend on acetylcholine to signal each other.
The highest level of gene activity was in rodents with added estrogen, while rats low in estrogen had low or nonexistent activity in the key genes.
"We don't think that estrogen makes nerve cells branch out in some way or form new connections so much as we believe it enhances their sensitivity to respond to and to send signals," says Koliatos. The immediate target for the work, he hopes, will be therapy for Alzheimer's disease (AD). "We know that there's disrupted cell communication in Alzheimer's," he says, "and we're hoping estrogen could enhance what communication is left."
Recent studies elsewhere that Koliatsos says are "beyond question" have shown that estrogen on its own doesn't seem to slow the disease in people who already have it. "But," he says, "perhaps estrogen could work in tandem with existing drugs to improve their effect." The few drugs on the market for AD boost acetylcholine and slow memory loss, but their benefits tail off all too quickly. "Perhaps estrogen could turn that around," says Koliatsos. "We're laying the scientific foundation for a new approach."
This information will be presented in a poster session on Thursday, Nov. 9 at 8 a.m., program 795.9, room C-74 of the Morial Convention Center
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