Neuronal brain-derived neurotrophic factor manipulates microglial dynamics

Glia. 2021 Apr;69(4):890-904. doi: 10.1002/glia.23934. Epub 2020 Oct 29.


Brain-derived neurotrophic factor (BDNF), a main member of the neurotrophin family that is active in the brain, supports neuronal survival and growth. Microglial BDNF affects both the structural and functional properties of neurons. In contrast, whether and how neuronal BDNF affects microglial dynamics remain largely undetermined. Here, we examined the effects of BDNF on the properties of microglia in the CA3 region of the hippocampus. We chose this site because the axonal boutons of hippocampal mossy fibers, which are mostly formed in the CA3 region, contain the highest levels of BDNF in the rodent brain. We transfected mouse dentate granule cells with an adeno-associated virus that encodes both a BDNF short hairpin RNA (shRNA) and red fluorescent protein to examine the effects of mossy fiber-derived BDNF on microglia. Based on immunohistochemistry, BDNF knockdown with an shRNA resulted in an increase in microglial density in the mossy fiber pathway and increased engulfment of mossy fiber axons by microglia. In addition, we performed time-lapse imaging of microglial processes in hippocampal slice cultures to examine the effects of BDNF on microglial motility. Time-lapse imaging revealed increases in the motility of microglial processes and the engulfment of mossy fiber synapses by microglia when BDNF signaling was pharmacologically blocked. Thus, neuronal BDNF prevents microglia from engulfing mossy fiber synapses in the hippocampus.

Keywords: BDNF; hippocampus; microglia; neuroplasticity; phagocytosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain-Derived Neurotrophic Factor* / genetics
  • Brain-Derived Neurotrophic Factor* / metabolism
  • Hippocampus / metabolism
  • Mice
  • Microglia* / metabolism
  • Mossy Fibers, Hippocampal / metabolism
  • RNA, Small Interfering / genetics


  • Brain-Derived Neurotrophic Factor
  • RNA, Small Interfering