title: Mechanisms underlying the interactions between rapid estrogenic and BDNF control of synaptic connectivity.
abstract: The effects of the steroid hormone 17β-estradiol and the neurotrophin brain-derived neurotrophic factor (BDNF) on neuronal physiology have been well investigated. Numerous studies have demonstrated that each signal can exert powerful influences on the structure and function of synapses, and specifically on dendritic spines, both within short and long time frames. Moreover, it has been suggested that BDNF is required for the long-term, or genomic, actions of 17β-estradiol on dendritic spines, via its ability to regulate the expression of neurotrophins. Here we focus on the acute, or rapid effects, of 17β-estradiol and BDNF, and their ability to activate specific signalling cascades, resulting in alterations in dendritic spine morphology. We first review recent literature describing the mechanisms by which 17β-estradiol activates these pathways, and the resulting alterations in dendritic spine number. We then describe the molecular mechanisms underlying acute modulation of dendritic spine morphology by BDNF. Finally, we consider how this new evidence may suggest that the temporal interactions of 17β-estradiol and BDNF can occur more rapidly than previously reported. Building on these new data, we propose a novel model for the interactions of this steroid and neurotrophin, whereby rapid, non-genomic 17β-estradiol and acute BDNF signal in a co-operative manner, resulting in dendritic spine formation and subsequent stabilization in support of synapse and circuit plasticity. This extended hypothesis suggests an additional mechanism by which these two signals may modulate dendritic spines in a time-specific manner.
authors.affiliation: Department of Neuroscience & Centre for the Cellular Basis of Behaviour, The James Black Centre, Institute of Psychiatry, King's College London, London SE5 9NU, UK. deepak.srivastava@kcl.ac.uk
authors.forename: D P
authors.initials: DP
authors.lastname: Srivastava
authors.forename: K M
authors.initials: KM
authors.lastname: Woolfrey
authors.forename: P D
authors.initials: PD
authors.lastname: Evans
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D049229:Dendritic Spines / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism*; D006801:Humans; D009473:Neuronal Plasticity / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D004967:Estrogens