A coming-of-age story: adult neurogenesis or adolescent neurogenesis in rodents?

Abstract

It is surprising that after more than a century using rodents for scientific research, there are no clear, consensual, or consistent definitions for when a mouse or a rat becomes adult. Specifically, in the field of adult hippocampal neurogenesis, where this concept is central, there is a trend to consider that puberty marks the start of adulthood and is not uncommon to find 30-day-old mice being described as adults. However, as others discussed earlier, this implies an important bias in the perceived importance of this trait because functional studies are normally done at very young ages, when neurogenesis is at its peak, disregarding middle aged and old animals that exhibit very little generation of new neurons. In this feature article we elaborate on those issues and argue that research on the postnatal development of mice and rats in the last 3 decades allows to establish an adolescence period that marks the transition to adulthood, as occurs in other mammals. Adolescence in both rat and mice ends around postnatal day 60 and therefore this age can be considered the onset of adulthood in both species. Nonetheless, to account for inter-individual, inter-strain differences in maturation and for possible delays due to environmental and social conditions, 3 months of age might be a safer option to consider mice and rats bona fide adults, as suggested by The Jackson Labs.

Modelling adult neurogenesis in the aging rodent hippocampus: a midlife crisis

“…As previously stressed (Snyder, 2019;Arellano et al, 2024), many of the functional studies supporting an important role for new neurons used very young, in many cases adolescent animals, that exhibit larger rates of neurogenesis, up to 7-8% according to our model (Table 1). If we consider the potential contribution of preferential recruitment of DFNs at those early ages, the model indicates that up to 30% of DFNs could be activated during normal DG activity (although see Stone et al, 2011;Dieni et al, 2013).…”

“…Another issue is the age of the animals whose data were used for our model. Most were 5-8 weeks old when injected with BrdU, meaning they were adolescent and not adult, as extensively discussed elsewhere (Arellano et al, 2024). This might imply that there could be differences in cell differentiation dynamics and survival ratios that might change in adult and aging animals.…”

“…In the context of adult neurogenesis, adulthood has been timed after weaning (at postnatal day 21), reasoning that by that age, the adult neurogenic niche, the subgranular zone (SGZ) of the dentate gyrus, has acquired its definitive structure ( Kempermann, 2011 ); or more commonly, adulthood have been timed with sexual maturity, normally defined as achieving sexual reproduction and thus starting at puberty, around P30 ( Kempermann, 2011 ). However, puberty is poorly correlated with successful mating, pregnancy, or maternal care, and it seems more reasonable to equate sexual maturity not just with the capacity for reproduction, but with the ability to reproduce and raise offspring successfully, that will be achieved at the end of the postpuberal adolescence period, a maturational stage that involves hormonal, physiological, neurological and behavioural changes that allow for successful reproduction ( Arellano et al, 2024 ). Adolescence ends around P60 in both rats and mice, marking the beginning of adulthood ( Arellano et al, 2024 ), and thus in this work we will consider P60 as the onset of adulthood for both species.…”

“…However, puberty is poorly correlated with successful mating, pregnancy, or maternal care, and it seems more reasonable to equate sexual maturity not just with the capacity for reproduction, but with the ability to reproduce and raise offspring successfully, that will be achieved at the end of the postpuberal adolescence period, a maturational stage that involves hormonal, physiological, neurological and behavioural changes that allow for successful reproduction ( Arellano et al, 2024 ). Adolescence ends around P60 in both rats and mice, marking the beginning of adulthood ( Arellano et al, 2024 ), and thus in this work we will consider P60 as the onset of adulthood for both species.…”

“…Since adulthood includes most of the lifespan in mammals, we will consider more meaningful subperiods: young adults, corresponding to peak reproduction (~2–7 month-old for mice and ~2–6 month-old for rats); middle age, corresponding to reproductive senescence in females (~8–14 month-old in mice and ~7–14 month-old in rats); and old age, corresponding to a post-reproductive (anestrous) period in females (~15–30 month-old in mice and ~15–21-month-old in rats) as previously described ( Arellano et al, 2024 ).…”