On December 14, 20’s0’s4, the first batch of a special group of rodents came out of the laboratory of biochemist Vânia Ferreira Prado, at the Federal University of Minas Gerais (UFMG): mice genetically altered not to make efficient use of acetylcholine, one of the chemical messengers responsible for the transmission of the command from one nerve cell to another. Developed by Vânia and her husband, pharmacist Marco Antonio Prado, the rodents went on to the laboratory of neuroscientist Ivan Izquierdo, in the Pontifical Catholic University of Rio Grande do Sul (PUC-RS), where they underwent a series of memory tests.
Incapable of releasing quickly the acetylcholine that they make, these mice show problems of memory and muscular weakness. They recognize neither objects nor other mice that were presented to them minutes before. They are also less resistant to physical effort: they fall down exhausted after five minutes of running, while normal mice manage to run on a treadmill for almost one hour, as shown by experiments done by the groups of Izquierdo and of the Prado couple, described in an article in the September issue of the Neuron magazine. ?We managed to produce animals that may help us to understand in a more precise way the importance of acetylcholine for the functioning of the organism” claims Marco Antonio.
Ever since German physician and pharmacologist Otto Loewi found, in 1921, that acetylcholine – the first neurotransmitter to be identified, formed from acetic acid and choline – acted in the communication between the nerve cells, people have been trying to discover how and in which physiological processes it acts. It is known, for example, that the lack of acetylcholine hampers learning and hinders the formation of the memory, but the details are not known. ?There are indications that it helps to maintain concentration, essential for recording information” Marco Antonio says.
Other models
Outside the central nervous system, this neurotransmitter acts in the communication between nerves and muscles, or between nerves and glands, like the suprarenal glands, which produce the adrenaline hormone. “Our mice” says the researcher, from the UFMG, “can be useful for testing medicines against memory loss connected with a reduction in the levels of acetylcholine and the characteristic debility of some muscular diseases (myasthenia).”
It is not the first time that genetically altered rodents have been bred to simulate the lack of acetylcholine or difficulty in using it – and to be used as a biological model for Alzheimer’s disease. There are animals that produce and release normal rates of acetylcholine, but that do not manage to use it, because they are missing the molecules to which the neurotransmitter adheres to activate the nerve cells. The mice bred by Vânia and Marco Antonio, in partnership with researchers from Duke University, United States, are different: they produce acetylcholine normally, but they do not use it adequately, because its release is less efficient than necessary.
Marco Antonio bets that this mismatch in the release of acetylcholine is associated with the effects of Alzheimer’s disease on the memory. “some researchers that are studying Alzheimer’s disease are preoccupied with the enzyme that produces the acetylcholine” says the pharmacist from UFMG, “but this enzyme can exist in a lower quantity, and even so the animal produces normal levels of this neurotransmitter, whereas the diminished release of acetylcholine alters the physical and mental behavior of the mice. Besides these animals that release acetylcholine more slowly into the central nervous system and in the other nerves of the body, the couple from Minas has now generated another lineage of mice, which manifests this effect only in the brain.
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