Protracted neuronal maturation in a long-lived, highly social rodent

Abstract

Naked mole-rats are a long-lived rodent species (current lifespan >37 years) and an increasingly popular biomedical model. Naked mole-rats exhibit neuroplasticity across their long lifespan. Previous studies have begun to investigate their neurogenic patterns. Here, we test the hypothesis that neuronal maturation is extended in this long-lived rodent. We characterize cell proliferation and neuronal maturation in established rodent neurogenic regions over 12 months following seven days of consecutive BrdU injection. Given that naked mole-rats are eusocial (high reproductive skew where only a few socially-dominant individuals reproduce), we also looked at proliferation in brain regions relevant to the social-decision making network. Finally, we measured co-expression of EdU (newly-born cells), DCX (immature neuron marker), and NeuN (mature neuron marker) to assess the timeline of neuronal maturation in adult naked mole-rats. This work reaffirms the subventricular zone as the main source of adult cell proliferation and suggests conservation of the rostral migratory stream in this species. Our profiling of socially-relevant brain regions suggests that future work which manipulates environmental context can unveil how newly-born cells integrate into circuitry and facilitate adult neuroplasticity. We also find naked mole-rat neuronal maturation sits at the intersection of rodents and long-lived, non-rodent species: while neurons can mature by 3 weeks (rodent-like), most neurons mature at 5 months and hippocampal neurogenic levels are low (like long-lived species). These data establish a timeline for future investigations of longevity- and socially-related manipulations of naked mole-rat adult neurogenesis.