Oral Presentation The International Congress of Neuroendocrinology 2014

A novel pathway by which 17β-estradiol modulates spatial memory via regulation of parvalbumin positive interneurons is disrupted in BDNF heterozygous mice. (#41)

Candace Wu 1 , Xin Du 1 , Maarten van den Buuse 1 , Rachel A Hill 1
  1. Florey Institute for Neuroscience and Mental Health, Parkville, VIC, Australia

Background: Cognitive deficits are a core feature of schizophrenia and are untreated by current antipsychotics. Brain-derived neurotrophic factor (BDNF) and estradiol enhance cognition. Parvalbumin (PV) positive GABAergic interneurons regulate neuronal synchrony and cognitive function, and are dysfunctional in schizophrenia. We recently found that estradiol regulates the expression of hippocampal PV, via BDNF signalling.
Methods: In the current study, we further explored the interaction between estradiol, BDNF and PV and their role in regulating cognition. WT and BDNF heterozygous (+/-) (50% BDNF) mice were ovariectomized (OVX) at 5 weeks of age and simultaneously received either saline, estradiol or progesterone treatment for 7 weeks. At young adulthood mice were tested for spatial (Y-maze), and recognition memory (novel object recognition). Hippocampal protein expression of BDNF and PV were assessed.
Results: OVX significantly impaired spatial and recognition memory in WT mice while estradiol but not progesterone recovered memory function. BDNF+/- intact mice showed a significant deficit in spatial, but not recognition memory compared to WT intact controls. However, OVX and hormone replacement had no significant effect on either spatial or recognition memory in BDNF+/- mice. BDNF and PV expression were significantly reduced by OVX in the hippocampus of WT mice compared to intact controls and estradiol recovered BDNF and PV expression. BDNF and PV expression were significantly reduced in the hippocampus of BDNF+/- compared to WT mice; however OVX and hormone treatment had no further impact on their expression.
Conclusions: Our data has revealed a novel pathway by which estradiol modulates cognition through regulation of hippocampal BDNF and PV. We also show for the first time that in contrast to WT mice, BDNF+/- mice show no response to hormone manipulation in both behavioural and molecular indices, suggestive of an altered neuroendocrine status. These data have significant implications for human carriers of BDNF gene polymorphisms.