Brain‐derived neurotrophic factor (BDNF) is required for the enhancement of hippocampal neurogenesis following environmental enrichment

TLDR

Neurogenesis persists in the adult hippocampus and is modulated by genetic and environmental factors, yet the mechanisms by which enriched environments enhance new neuron production remain unclear. The study aimed to determine whether neurotrophins, specifically BDNF and NT‑4, are necessary for environmental enrichment–induced hippocampal neurogenesis. Heterozygous BDNF (+/–) and NT‑4 (–/–) knockout mice, along with wild‑type littermates, were raised in standard or enriched conditions for eight weeks and received bromodeoxyuridine injections to label newborn cells. Enriched wild‑type and NT‑4–/– mice exhibited a two‑fold increase in hippocampal neurogenesis, whereas enriched BDNF +/– mice did not, demonstrating that BDNF—but not NT‑4—is required for the environmental induction of neurogenesis.

Abstract

Abstract Neurogenesis continues to occur in the adult mammalian hippocampus and is regulated by both genetic and environmental factors. It is known that exposure to an enriched environment enhances the number of newly generated neurons in the dentate gyrus. However, the mechanisms by which enriched housing produces these effects are poorly understood. To test a role for neurotrophins, we used heterozygous knockout mice for brain‐derived neurotrophic factor (BDNF +/– ) and mice lacking neurotrophin‐4 (NT‐4 –/– ) together with their wild‐type littermates. Mice were either reared in standard laboratory conditions or placed in an enriched environment for 8 weeks. Animals received injections of the mitotic marker bromodeoxyuridine (BrdU) to label newborn cells. Enriched wild‐type and enriched NT‐4 –/– mice showed a two‐fold increase in hippocampal neurogenesis as assessed by stereological counting of BrdU‐positive cells in the dentate gyrus and double labelling for BrdU and the neuronal marker NeuN. Remarkably, this enhancement of hippocampal neurogenesis was not seen in enriched BDNF +/– mice. Failure to up‐regulate BDNF accompanied the lack of a neurogenic response in enriched BDNF heterozygous mice. We conclude that BDNF but not NT‐4 is required for the environmental induction of neurogenesis.