Numbers of neurons in the retinal ganglion cell layer of the rat do not change throughout life.

BACKGROUND: There have been many assumptions made about neuronal loss in mammals due to aging. However, when we examined the retinal ganglion cell layer of a marsupial, the quokka, from 0.5 to 13.5 years of age, we found that the total neuron number did not decrease significantly even into extreme old age. The retinal area increased slowly throughout life, leading to a decrease in cell density. Neuronal death in the rat retina has been assumed, since the cell density has been seen to fall with age. However, a similar study to ours in the quokka has never been performed in the laboratory rat, the model for so many experimental investigations. OBJECTIVE: We decided to test the hypothesis that rats do not lose neurons due to aging and that an increase in retinal area, and not cell death, as previously suggested, might underlie the decreasing cell density seen in aging animals such as rats. METHODS: We kept laboratory rats under standard, unvarying conditions throughout the trial, sacrificing 3 animals every 3 months up to 30 months, and examined the retinal ganglion cell layer through adult life. RESULTS: We found that the numbers of neurons did not decrease in this species, even in the oldest rats. We also saw that the retinal area increased slowly with a concomitant slow decrease in mean neuronal density. Soma diameters of neurons gradually increased throughout life. CONCLUSIONS: When rats are kept under standard conditions, there is no neuronal loss in the retina during aging, although the cell density does decrease as a result of retinal expansion. It is not sufficient to measure retinal cell density to determine cell loss. In addition, it is important to know that in normal conditions there is no cell loss in the retinal ganglion cell layer as a result of aging. Any loss that is seen must be a result of additional factors.

Neurogenesis in the hippocampus of an adult marsupial.

In the adult eutherian brain, stem cells in the dentate gyrus continually divide throughout adult life and into old age producing new granule cells. However, it was not known whether this is also the case for marsupials. Previously, in fact, it was thought that marsupials did not have continued neurogenesis in the mature brain. Here we examined neurogenesis in the adult brain of a small marsupial, the fat-tailed dunnart, using 3H-thymidine to label newly generated cells. We showed that neurogenesis takes place in the adult dentate gyrus along its inner margin, as seen in eutherian mammals. Control animals had similar numbers of labeled cells 24 h and 1 month after 3H-thymidine injection. An enriched environment resulted in similar numbers of cells being generated as controls. However, there was a significant decline in the number of labeled cells one month later. Stress and old age resulted in significantly lower numbers of new cells being generated. In immunohistochemically treated control brains, 3H-thymidine-labeled cells at the early stage were sometimes GFAP positive, were not calbindin positive at either stage examined and at the later stage were PSA-NCAM positive. We hypothesize that, as seen in eutherian mammals, the new cells progressed from being GFAP positive at stem cell stage to PSA-NCAM positive during outgrowth of mossy fibers 1 month later, to calbindin positive when mature. It is possible that maturity of these cells was not reached by 1 month as marsupials have a slower metabolic rate and this species also undergoes daily periods of torpor.