Clues to nicotine's memory, plaque impact

Low concentrations of nicotine in the blood tend to boost volunteers' performance on tasks that require them to retain and interpret recently acquired information. This memory assist may stem from nicotine's ability to enhance the transmission of chemical messengers in a brain structure known as the hippocampus, according to a new report.

Unrelated, preliminary findings suggest that nicotine may also slow plaque formation in the brains of people with Alzheimer's disease.

Nicotine activates a class of receptors on hippocampal cells that typically responds to the neurotransmitter acetylcholine, explains neuroscientist Richard Gray of Baylor College of Medicine in Houston. Like naturally occurring acetylcholine, externally administered nicotine induces these so-called nicotinic acetylcholine receptors to bolster the actions of other neurotransmitters that facilitate memory, Gray and his colleagues assert.

Alzheimer's disease may derive, at least in part, from an inactivation of these hippocampal sites, known as alpha 7-type receptors, Gray's team theorizes in the Oct. 24 NATURE.

The new findings serve as "an important step toward [recognizing] nicotine as a powerful modulator of memory," state neuroscientists Daniel S. McGehee of the University of Chicago and Lorna W Role of Columbia University in an accompanying commentary.

Nonetheless, the activation of nicotinic acetylcholine receptors represents only one of many still poorly understood steps that underlie nicotine's effects on thinking and behavior, McGehee and Role contend. Controversial research has indicated that although low concentrations of nicotine aid performance on relatively simple memory tasks, high concentrations interfere with complex mental operations (SN: 1/16/93, p. 46).

Gray's group first established that low concentrations of nicotine, comparable to those observed in the bloodstream after a smoker has consumed a single cigarette, enhance the rate of nerve impulse transmission in rat hippocampal cells preserved in the lab. Nicotine also increases calcium concentrations in these cells, the researchers contend.

Their results support the theory that the alpha 7-type receptors activated by low doses of nicotine induce the release of calcium, which in turn leads to increased transmission of the neurotransmitter glutamate, they maintain.

Properly timed nicotinic acetylcholine receptor activity may ensure the success of this transmission process, the investigators propose. In people with Alzheimer's disease, the same receptors may fail to coordinate their diminished activity with the arrival of nerve impulses, the team suggests.

A separate investigation, published in the Oct. 22 BIOCHEMISTRY, provides preliminary evidence that nicotine may slow or prevent the formation of the plaque found in the brains of individuals with Alzheimer's disease.

These results may lead to the design of less toxic, nicotinelike compounds to prevent and treat the disease, asserts biochemist and study director Michael G. Zagorski of Case Western Reserve University in Cleveland.

In laboratory experiments, Zagorski and his coworkers examined the effect of high nicotine concentrations on a synthetic version of beta-peptide, a major precursor of plaque. Scientists suspect that various forms of beta-peptide orchestrate chemical reactions that result in the plaque deposits that characterize Alzheimer's disease.

Nicotine attaches to the synthetic beta-peptide and disrupts the chain of events thought to lead to plaque formation, Zagorski holds.

Researchers do not know whether nicotine retards plaque formation in Alzheimer's disease patients, he notes.

-B. Bower

Reprinted by permission