Differential regulation of BDNF, synaptic plasticity and sprouting in the hippocampal mossy fiber pathway of male and female rats

Neuropharmacology. 2014 Jan;76 Pt C(0 0):696-708. doi: 10.1016/j.neuropharm.2013.04.029. Epub 2013 May 6.


Many studies have described potent effects of BDNF, 17β-estradiol or androgen on hippocampal synapses and their plasticity. Far less information is available about the interactions between 17β-estradiol and BDNF in hippocampus, or interactions between androgen and BDNF in hippocampus. Here we review the regulation of BDNF in the mossy fiber pathway, a critical part of hippocampal circuitry. We discuss the emerging view that 17β-estradiol upregulates mossy fiber BDNF synthesis in the adult female rat, while testosterone exerts a tonic suppression of mossy fiber BDNF levels in the adult male rat. The consequences are interesting to consider: in females, increased excitability associated with high levels of BDNF in mossy fibers could improve normal functions of area CA3, such as the ability to perform pattern completion. However, memory retrieval may lead to anxiety if stressful events are recalled. Therefore, the actions of 17β-estradiol on the mossy fiber pathway in females may provide a potential explanation for the greater incidence of anxiety-related disorders and post-traumatic stress syndrome (PTSD) in women relative to men. In males, suppression of BDNF-dependent plasticity in the mossy fibers may be protective, but at the 'price' of reduced synaptic plasticity in CA3. This article is part of the Special Issue entitled 'BDNF Regulation of Synaptic Structure, Function, and Plasticity'.

Keywords: Area CA3; Estradiol; Hippocampus; Mossy fiber sprouting; Neurotrophin; Testosterone.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Estradiol / pharmacology
  • Estrogens / pharmacology
  • Female
  • Hippocampus / anatomy & histology*
  • Hippocampus / physiology
  • Male
  • Mossy Fibers, Hippocampal / anatomy & histology
  • Mossy Fibers, Hippocampal / drug effects
  • Mossy Fibers, Hippocampal / physiology*
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology*
  • Rats
  • Receptors, GABA / metabolism
  • Sex Characteristics*
  • Synapses / drug effects
  • Synapses / physiology*
  • gamma-Aminobutyric Acid / metabolism


  • Estrogens
  • Receptors, GABA
  • Estradiol
  • gamma-Aminobutyric Acid