Ant Pheromone May Aid Alzheimer's Patients

February 02, 1998

ITHACA, N.Y. -- The pheromone trail laid down by an "Aphaenogaster rudis" ant to help the ant and its recruited nest mates find their way back to prey they plan to kill -- contains a chemical now undergoing clinical trials as a possible Alzheimer's disease treatment, Cornell University chemists report in the January 1998 issue of the German journal "Naturwissenschaften".

Anabaseine, whose chemical analog GTS-21 stimulates the nicotine receptor sites in the brains of Alzheimer's patients and helps reduce memory loss, is one of four components found by Cornell researchers in secretions from the poison glands of "A. rudis" ants, a common species in the Northeast United States.

"However, this doesn't mean we should grow ants to treat Alzheimer's patients," said Athula B. Attygalle, senior research associate in the Cornell Institute for Research in Chemical Ecology (CIRCE) laboratory of Professor Jerrold Meinwald as well as director of the Mass Spectrometry Facility in Cornell's Department of Chemistry. "Synthetic versions of anabaseine can be made much more easily for medicinal purposes. We're interested in these neurotoxins because they're found in 'lower' animals, such as marine worms and ants, and even plants, and they seem to have an effect on the human brain."

Friedrich Kern, a visiting scientist in chemistry who observed "A. rudis" ant behavior in the laboratory as well as in wooded areas near Ithaca, described how one chemical cocktail serves several purposes for the ants: "This tiny ant needs help subduing prey that can be 10 to 15 times its size, so the ant returns to the nest and tries to recruit some nest mates," Kern explained. "The ant marks the route by dragging its sting along the ground like an ink pen and leaves traces of this four-part chemical cocktail from its poison gland.

"The chemical is a recruitment pheromone," Kern continued, "and when ants sense the pheromone, they become excited enough to follow the trail back to the prey -- perhaps a worm or grub or an adult insect of some kind. Then they attack the prey with their stings, inject a neurotoxin that paralyzes muscles and drag the prey back to the nest."

Gas chromatographic and mass spectrometric analyses in the Cornell laboratory identified four components in the multipurpose fluid from the ants' poison glands. They are N-isopentyl-2-phenylethylamine, a key compound never before identified from nature; anabaseine (3,4,5,6-tetrahydro-2,3'-bipyridine ); anabasine [3-(2-piperidinyl)pyridine]; and a fourth chemical never before found in ants, 2,3'-bipyridyl.

Further studies with the ants showed that the four chemicals together act synergistically, and that individual chemicals do not induce the same behavioral response. Describing a laboratory experiment with ants following a trail of the four-part cocktail that diverged into four trails of individual components, the chemists reported in "Naturwissenschaften". "They searched around, but not a single ant was able to proceed and follow any of the continuation trails."

"As we continue to investigate the roles of chemicals in the lives of various species, we find certain compounds turning up in very different organisms," Attygalle said. "Here we have pyridine-based alkaloids that appear in tobacco leaves, in marine worms as defensive compounds and in ants to help them obtain food."


On the Pheromone Trail

"Chemical Communication Among Ants"

Source: Athula Attygalle, Ph.D., Mass Spectrometry Facility, Cornell Department of Chemistry

-- MORE THAN SEX: In the animal world, the chemical-based signals called pheromones do more than attract the opposite sex. Alarm pheromones, which are released when one aphid is crushed, send nearby aphids fleeing for their lives. Territorial marking pheromones, left behind when a cat rubs its cheek on a human's leg, tell other cats to whom the human belongs. Likewise, dogs don't really have to urinate every few yards along their morning walk; they, too, are leaving a chemical calling card to mark a territory. Kin-recognition pheromones tell insects who's family and who's not, even within the same species, and non-kin trying to enter a nest without the appropriate pheromone are fought off or killed. Recruitment pheromones, such as those produced by the "Aphaenogaster rudis" ants, rally nest mates to follow a pheromone-scented trail to a source of food; by the time the ants reach the prey item, they are excited enough to attack with venom that contains the pheromone they were following.

-- ZIGZAG PATH: The pheromone trail left by an ant, such as the "A. rudis", is not the shortest distance between two points to begin with, and ants following the trail appear to zigzag along the way. That is because the pheromone receptors in the tips of their two antennae orient them to the source of the pheromone and direct them to turn left or right. When they veer off the trail to the right, the right-hand antennae -- receiving a weaker signal -- tell them to turn left. And if they overcompensate and zag too far to the left, the left-hand antennae make them steer to the right. An ant with only one antenna will only zig (or zag). And if ants' antennae become crossed, they are hopelessly disoriented.

-- EVOLUTION OF THE CHARISMA CHEMICAL: Not every ant species can draw a crowd with chemically sophisticated recruitment pheromones. The Myrmicine ants studied by Cornell researchers sometimes recruited seven or eight helpers. But army ants, generally regarded as being more advanced in an evolutionary sense, can summon thousands of compatriots with a single chemical signal. And more primitive ants, lacking a recruitment pheromone, leave no detectable trail. Setting off on a mission, a primitive ant practices tandem running -- that is, if it can persuade one other ant to come along.

-- SENSITIVE SENSORS: Pheromone receptors and the biological signaling apparatus that go with them are as sensitive as the finest analytical-chemistry instruments. Cornell researchers test this super-sensing ability by measuring the electrical current passing through an ant's antenna as different chemicals, separated from a complex mixture by a gas chromatograph, are presented to the receptor at the tip of the antenna. Invariably, the antennae transmit signals only when the appropriate pheromone (or another important chemical for the ant) is detected. Ants can detect just a few parts of their pheromone in a billion parts of air. And when the electrical signal passes through their antennae, only 0.1- to 2-millivolt potential differences are created. No wonder their batteries never seem to run down.


Cornell University

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