Elderly animals do not lose neurons, indicates study

A study conducted with cavies by USP scientists shows that elderly animals do not have a reduced number of neurons and that nerve cell division continues in old age.

By Fábio de Castro

Agência FAPESP – A study conducted with cavies by researchers at Universidade de São Paulo (USP) has shown that elderly animals do not suffer from a reduction in the number of neurons in the peripheral autonomic nervous system, the part of the nervous system that is found in several organs outside of the brain.

The study was published in the International Journal of Developmental Neuroscience, the official magazine of the International Society for Developmental Neuroscience.

The study is part of a master’s thesis by Aliny Antunes Barbosa Lobo Ladd at the Veterinary and Zootechny School (FMVZ) at USP. The study was funded through a FAPESP Fellowship and was supervised by Professor Antonio Augusto Coppi, who oversees the Laboratory of Stochastic Stereology and Chemical Anatomy (LSSCA) at the Department of Surgery within USP’s Veterinary and Zootechny School (FMVZ-USP).

The study is part of a series of group research projects that reinforce the theory that elderly animals do not necessarily experience a reduction in neuron numbers. “Furthermore, to its credit, the study also observed neurons dividing in elderly animals – something that until a few years ago was considered impossible in the medical literature,” Coppi explains to Agência FAPESP.

According to Coppi, it is already possible to affirm that aging does not necessarily correspond to a loss of nerve cells. This loss, he says, has been taken as dogma in neuroscience for decades.

“From 1954 to 1984, several studies indicated that there was neuron loss during the aging process. However, we attributed this conclusion to the bi-dimensional method that was used to quantify nerve cells at the time. Beginning in 1984, when a Danish group published the first study using the three dimensional stereology method called the ‘Disector,’ counting cells became much more accurate and precise,” he explained.

Since then, the international scientific community has begun to repeat the studies conducted in previous decades, with more accurate results. However, most of these studies have been geared toward the central nervous system. FMVZ-USP’s studies specifically focus on neurons from the autonomic nervous system, seeking to confirm the conclusions of the other studies conducted in the brain.

“We initiated this line of research in 2002, and this is the seventh international study that we have published on the topic. These studies are confirming that the number of neurons in the peripheral nervous system does not necessarily decrease during aging. On the contrary, the majority of the neurons remain stable,” says Coppi.

Cell division

The group has already conducted studies that incorporated Parkinson and Huntington disease models using rats, guinea pigs, horses, dogs, cats, capybaras, pacas, common agoutis and now the cavy, which is a South American rodent of the family Caviidae and includes the capybara, coypu and agouti. Cavies are considered elderly after they reach three and a half years, making them a desirable animal model for studies involving aging.

“Through immunohistochemical methods in combination with stereology, we detected uninucleate and binucleate neurons in the midst of their division processes in elderly animals. Our hypothesis is that the number of dividing nerve cells is greater than the number of dying neurons, and this allows the total number of neurons to remain stable,” explains Coppi.

Among the many animal models studied by the group over the last ten years, the only exception noted was in guinea pigs. “In the case of guinea pigs, we saw a 21% reduction in the total number of neurons among aged animals. We do not know how to explain this reduction. However, in dogs, we saw an incredible increase in the number of neurons in elderly animals: 1700%,” he said.

Despite these exceptions, this set of studies shows that the trend in aging populations is one of stability or even an increase in the total number of neurons. “This data alone discredits the canonical view that the number of neurons always decreases with age,” Coppi affirms.

The difference in the study with cavies, according to Coppi, is that the team was able to observe neurons in the autonomic nervous system in the midst of cellular division for the first time. The dividing neurons were quantified in three dimensions using the optical fractionator stereological method.

“This time, we used immunohistochemical markers to detect cells that were dividing. We showed that the number of dividing cells is proportionally constant in each age group. In this way, the total number of cells remains exactly the same in each of the four age groups that we observed: neonatal animals, youths, adults and the elderly,” he explains.

The article “SCG postnatal remodeling – hypertrophy and neuron number stability – in Spix's Yellow-toothed Cavies (Galea spixii)” by Aliny Ladd, Antonio Coppi and others, can be read by subscribers of International Journal of Developmental Neuroscience at www.ncbi.nlm.nih.gov.

For more information on this study: www2.fmvz.usp.br/lssca e [e-mail].