Life-long addition of neurons occurs in parts of the nervous systems of both vertebrates and invertebrates. Although the functional meaning of adult neurogenesis is not known in most cases, there is considerable interest in understanding the mechanisms of adult neurogenesis, with the hope of finding new treatments to heal damaged nervous tissue. Adult neurogenesis might also function in learning and memory, since one of the systems where it is found is the hippocampus of mammals. The timing and rate of adult neurogenesis appears to be controlled by a wide range of mechanisms, such as hormonal cycles, physical activity and social interactions. In a recent paper in the Journal of Neurobiology, Barbara Beltz and her colleagues at Wellesley college show that the proliferation of nerve cells can also be under circadian control.
Some groups of neurons in the olfactory pathway of the American lobster (Homarus americanus) continue to proliferate throughout the lobster's life, so the authors decided to investigate circadian control of neurogenesis in the lobster's olfactory lobe. Beltz's team used a simple protocol to monitor cell proliferation. They labeled newly developed cells with bromodeoxyuridine (BrdU), which is incorporated into DNA in place of thymidine during mitosis and can be detected by antibody-staining. The team placed juvenile lobsters in seawater that contained BrdU for 3 h periods at different times during an artificial light/dark cycle and then counted the newly proliferated cells that carried the BrdU label.
The authors found dramatic differences in the numbers of neurons that proliferated over the 3 h incubation period, depending on the point in the artifical light/dark cycle when the lobsters were incubated with BrdU. The highest numbers of new neurons were found when the incubation took place around the artificial dusk, while minimal numbers were found around dawn.
Beltz and her team also investigated the nature of the diurnal signal that caused this effect by altering the animals' light/dark cycle. The animals were kept in a normal 12 h:12 h light/dark cycle for 2 weeks before they were moved into complete darkness for 3 days. These animals retained the diurnal variation of neurogenesis, so the underlying biological rhythm appears to be endogenous. The team also found that this endogenous rhythm can be resynchronized by exposure to light. They tested a second group of lobsters that were kept in a reversed light/dark cycle and found that the rhythmicity of neurogenesis was also shifted by 12 h, so that the number of new cells still peaked around the subjective dusk and minimal counts were still found around subjective dawn.
Most animals show activity patterns tightly linked to a diurnal cycle, so hunting, feeding or social interactions are dependent on the time of day. It is also known that hormonal levels can be under circadian control. Hence, most factors that have been found to regulate neurogenesis in the adult nervous system are themselves controlled by diurnal rhythms. It is not clear to what extent circadian regulation of neurogenesis acts through these factors or if it has a more direct effect. However, the time of day could be an important cue for regulation of nerve cell proliferation in many systems.
- © The Company of Biologists Limited 2003