Dentate gyrus neurons that are born at the peak of development, but not before or after, die in adulthood

Abstract

IntroductionIn the dentate gyrus of the rodent hippocampus, neurogenesis begins prenatally and continues to the end of life. Adult‐born neurons often die in the first few weeks after mitosis, but those that survive to 1 month persist indefinitely. In contrast, neurons born at the peak of development are initially stable but can die later in adulthood. Physiological and pathological changes in the hippocampus may therefore result from both the addition of new neurons and the loss of older neurons. The extent of neuronal loss remains unclear since no studies have examined whether neurons born at other stages of development also undergo delayed cell death.MethodsWe used BrdU to label dentate granule cells that were born in male rats on embryonic day 19 (E19; before the developmental peak), postnatal day 6 (P6; peak), and P21 (after the peak). We quantified BrdU+ neurons in separate groups of rats at 2 and 6 months post‐BrdU injection to estimate cell death in young adulthood.ResultsConsistent with previous work, there was a 15% loss of P6‐born neurons between 2 and 6 months of age. In contrast, E19‐ or P21‐born neurons were stable throughout young adulthood.DiscussionDelayed death of P6‐born neurons suggests these cells may play a unique role in hippocampal plasticity adulthood, for example, by contributing to the turnover of hippocampal memory. Their loss may also play a role in disorders that are characterized by hippocampal atrophy.

Maintaining Aging Hippocampal Function with Safe and Feasible Shaking Exercise in SAMP10 Mice

“…Our data suggest that enhanced shaking exercise positively affects the behavioral flexibility of a mouse and improves the retention of previously acquired information and also facilitates learning. Most DG cells are developed during early embryonic development [19]. The continual production of new neurons in the adult hippocampus was first reported in 1965 [20].…”

The neurotoxic effect of isoflurane on age‐defined neurons generated from tertiary dentate matrix in mice

“…Ciric et al. (2019) suggested 17% of P6‐born DG neurons showed delayed cell death after reaching maturity in young adult, suggesting the tertiary dentate matrix‐derived mature neurons might be more sensitive to the insults such as isoflurane exposure.…”

“…A great increase in granule cell population during the infantile and juvenile periods is principally derived from the tertiary dentate matrix (Schlessinger et al., 1975). Furthermore, the neurons generated from different sites were found to exhibit respective survival phenotypes (Ciric et al., 2019), suggesting their response to the anesthetics exposure may be not identical. Actually, even for the cells with the same origin site, the extent of cell death following the anesthetics exposure still depends on the developmental stage of these cells (Erasso et al., 2013).…”

Prolonged development of long-term potentiation at lateral entorhinal cortex synapses onto adult-born neurons

“…This may have therefore led to a reduction in LTP magnitude selectively in our mature adult-born group, since some of these recordings came from older animals. Given that mature neonatal-born neurons are more vulnerable to delayed cell death [95][96][97], it will be important to examine older animals and determine whether they are also more susceptible to age-related synaptic deterioration.…”