Neonatal Ethanol and Choline Treatments Alter the Morphology of Developing Rat Hippocampal Pyramidal Neurons in Opposite Directions

Neuroscience. 2018 Mar 15:374:13-24. doi: 10.1016/j.neuroscience.2018.01.031. Epub 2018 Feb 2.

Abstract

Some of the neurobehavioral deficits identified in children with Fetal Alcohol Spectrum Disorders (FASDs) have been recapitulated in a binge model of gestational third trimester-equivalent ethanol (EtOH) exposure, in which Sprague-Dawley rats are intragastrically intubated between post-natal day (PD) 4 and PD9 with high doses of EtOH. In this model, the ameliorating effects of choline (Chol) administration on hippocampus-dependent behaviors altered by EtOH have also been extensively documented. In the present study, we investigated the effects of EtOH (5 g/kg/day) and/or Chol (100 mg/kg/day) on morphometric parameters of CA1 pyramidal neurons by Golgi-Cox staining followed by Neurolucida tracing and analysis. We found that EtOH increased apical dendrite complexity in male and female pups neonatally exposed to EtOH. EtOH did not significantly affect basal dendrite parameters in female and male rats. Interestingly, Chol treatments decreased basal dendrites' length, number, and maximal terminal distance in male pups. When pups were co-treated with EtOH and Chol, Chol did not rescue the effect of EtOH. In conclusion, EtOH increases while Chol decreases dendritic length and arborization of hippocampal CA1 neurons in PD9 rats. We hypothesize that developmental EtOH exposure induces a premature maturation of neurons, leading to early restriction of neuronal plasticity while Chol treatments delay the normal program of neuronal maturation and therefore prolong the window of maximal plasticity. Chol does not prevent the effects of developmental alcohol exposure on hippocampal pyramidal neurons' morphology characterized in the present study, although whether prolonged Chol administration after developmental EtOH exposure rectifies EtOH damage remains to be assessed.

Keywords: Fetal Alcohol Spectrum Disorders; Golgi–Cox staining; apical dendrites; basal dendrites; hippocampus; pyramidal neurons.

Publication types

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

MeSH terms

  • Animals
  • Animals, Newborn
  • CA1 Region, Hippocampal / drug effects
  • CA1 Region, Hippocampal / growth & development*
  • CA1 Region, Hippocampal / pathology*
  • Cell Size / drug effects
  • Choline / toxicity*
  • Dendrites / drug effects
  • Dendrites / pathology
  • Disease Models, Animal
  • Ethanol / toxicity*
  • Female
  • Fetal Alcohol Spectrum Disorders / pathology*
  • Male
  • Pyramidal Cells / drug effects
  • Pyramidal Cells / pathology*
  • Random Allocation
  • Rats, Sprague-Dawley

Substances

  • Ethanol
  • Choline