Short‐term and long‐term survival of new neurons in the rat dentate gyrus

Abstract

New neurons continue to be generated in the dentate gyrus throughout adulthood. Previous studies have shown that a significant proportion of new granule cells labeled with the thymidine analogue bromodeoxyuridine (BrdU) are lost from the adult dentate gyrus within 2 weeks. How long this loss continues and the extent to which it represents cell death, as opposed to dilution of label, is unclear. To address these questions, adult rats were injected with BrdU, and BrdU labeling in the dentate gyrus was compared at several survival time points. Double labeling with BrdU and the cell cycle marker Ki-67 showed that BrdU is detectable for up to 4 days in some cells that continue to divide, indicating that any decrease in the number of BrdU-labeled cells after 4 days is likely to reflect cell death rather than BrdU dilution. Death of new cells in the granule cell layer occurred at a steady rate between 6 and 28 days after labeling, resulting in loss of 50% of BrdU-labeled cells over this 22-day period. New granule cells that survived this first month lived for at least 5 additional months. In contrast, 26% of the granule cells labeled with BrdU at the peak of dentate gyrus development on postnatal day (P) 6 died between 1 and 6 months after labeling. These findings suggest that granule cells born during adulthood that become integrated into circuits and survive to maturity are very stable and may permanently replace granule cells born during development.

Adult neurogenesis is functionally associated with AD-like neurodegeneration

“…The number of new neurons that can survive over four weeks is relatively stable and thus this time scale has been considered as an essential criterion to judge whether new neurons have the potential to develop into functional units in the neuronal network. Indeed, there is evidence that the survival of new neurons over four weeks makes them express electrophysiological properties similar to other granule cells in the dentate gyrus (van Praag, et al, 2000, Dayer, et al, 2003, Overstreet-Wadiche, et al, 2006. Interestingly, we have found that neurodegeneration-triggered new neurons in PS1/PS2-KO mice survive over a period of four weeks at ESND, implying that this neurogenesis might be potentially functional.…”

“…Adult neurogenesis consists of four distinctive stages, proliferating from stem or progenitor cells (proliferation), differentiating into immature neurons (differentiation), developing into mature neurons (new neuron generation), and migrating into neuronal network, axon/dendrite targeting and synaptic integrating (survival or functional neurogenesis) (Gage, 2000, Dayer, et al, 2003. A well-designed BrdU injection paradigm is able to specifically address these distinctive neurogenic processes.…”

Effect of neural precursor proliferation level on neurogenesis in rat brain during aging and after focal ischemia

“…Although greater than 9,000 new cells are produced per day in the adult rodent hippocampus [7], 60-80% of them degenerate within one month [13]. We and others have reported a gradual decline of neurogenesis with normal aging in rats and mice [8,19,23], which could be due to either decreased NPC neuroproliferation or increased NPC death.…”

“…In support of this possibility, NPCs show increased proliferation in response to brain insults such as ischemia [18], migrate toward sites of brain damage [1], and can differentiate into functional neurons [25]. However, only a subset of newborn SVZ neurons migrate into the olfactory bulb (OB) and differentiate into mature neurons [9], whereas the majority undergo programmed cell death [13].…”

Is there a link between adult neurogenesis and learning?

“…At an information processing level, how does a new population of neurons interact with those neurons that were generated during development and how do these interactions lead to the formation of new memories without destroying old memories? Addressing most of these questions will require a better understanding of the functional maturation of adultgenerated neurons (Carlen et al, 2002;Dayer et al, 2003;Ambrogini et al, 2004b) as well as insight into the differences and similarities between neurons generated during development vs. those produced in adulthood. Until now, addressing such issues has been inhibited by technical limitations but may be more feasible given a number of recent advances.…”