Adolescent bisphenol-A exposure decreases dendritic spine density: role of sex and age

Synapse. 2014 Nov;68(11):498-507. doi: 10.1002/syn.21758. Epub 2014 Jul 15.

Abstract

Bisphenol-A (BPA), a common environmental endocrine disruptor, modulates estrogenic, androgenic, and antiandrogenic effects throughout the lifespan. We recently showed that low dose BPA exposure during adolescence increases anxiety and impairs spatial memory independent of sex. In this study, six week old Sprague Dawley rats (n=24 males, n=24 females) received daily subcutaneous injections (40 µg/kg bodyweight) of BPA or vehicle for one week. Serum corticosterone levels in response to a 1 h restraint stress and spine density were examined at age 7 (cohort 1) and 11 (cohort 2) weeks. Adolescent BPA exposure did not alter stress dependent corticosterone responses but decreased spine density on apical and basal dendrites of pyramidal cells in the medial prefrontal cortex (mPFC) and hippocampal CA1 region (CA1). Sex differences in spine density were observed on basal dendrites of the mPFC and CA1 with females having greater spine density than males. This sex difference was further augmented by both age and treatment, with results indicating that BPA-dependent decreases in spine density were more pronounced in males than females on mPFC basal dendrites. Importantly, the robust neuronal alterations were observed in animals exposed to BPA levels below the current U.S.E.P.A. recommended safe daily limit. These results are the first demonstrating that BPA given during adolescence leads to enduring effects on neural morphology at adulthood. Given that humans are routinely exposed to low levels of BPA through a variety of sources, the decreased spine density reported in both male and female rats after BPA exposure warrants further investigation.

Keywords: corticosterone; hippocampus; medial prefrontal cortex.

Publication types

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

MeSH terms

  • Age Factors
  • Animals
  • Benzhydryl Compounds / toxicity*
  • CA1 Region, Hippocampal / cytology
  • CA1 Region, Hippocampal / drug effects
  • CA1 Region, Hippocampal / growth & development
  • Corticosterone / blood
  • Dendritic Spines / drug effects*
  • Endocrine Disruptors / toxicity*
  • Female
  • Male
  • Phenols / toxicity*
  • Prefrontal Cortex / cytology
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / growth & development
  • Pyramidal Cells / cytology
  • Pyramidal Cells / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Sex Factors

Substances

  • Benzhydryl Compounds
  • Endocrine Disruptors
  • Phenols
  • bisphenol A
  • Corticosterone