Distinct effects of perinatal exposure to fluoxetine or methylmercury on parvalbumin and perineuronal nets, the markers of critical periods in brain development

Int J Dev Neurosci. 2015 Aug;44:55-64. doi: 10.1016/j.ijdevneu.2015.05.006. Epub 2015 May 19.


The in utero exposure to common chemical stressors, environmental pollutant methylmercury and antidepressant fluoxetine, results in behavioral impairments persistent into adulthood. Modulation of critical periods in brain development may alter proper network formation and lastingly impair brain function. To investigate whether early-life stressors can modulate critical periods, we analyzed the development of parvalbumin (PV) and perineuronal nets (PNNs) in the dentate gyrus and CA1 area of the hippocampus and the basolateral amygdala in mice perinatally exposed to either fluoxetine or methylmercury. The number of PV and PNN neurons, and PV intensity, were analyzed by fluorescent immunohistochemistry at the postnatal ages P17 (ongoing critical period) and P24 (closing critical period). The exposure to fluoxetine did not affect the number of PV cells and PV intensity but decreased PNN formation around the cells at P17 and P24 in all tissues. In contrast, perinatal methylmercury inhibited the development of PV interneurons and PV expression at P17 only, but at P24 these parameters were restored. Methylmercury strongly increased PNN formation from P17 to P24 in the amygdala only. We suggest that perinatal fluoxetine and methylmercury might delay the closure and the onset, respectively, of the critical periods in the amygdala and hippocampus.

Keywords: Critical periods in development; Neuronal maturation; Oxidative stress; Parvalbumin; Perineuronal nets; Prenatal stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Animals, Newborn
  • Brain* / growth & development
  • Brain* / metabolism
  • Brain* / pathology
  • Cell Count
  • Extracellular Matrix Proteins / metabolism
  • Female
  • Fluoxetine / toxicity*
  • Male
  • Methylmercury Compounds / toxicity*
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Confocal
  • Nerve Net / metabolism
  • Nerve Net / pathology*
  • Parvalbumins / metabolism*
  • Pregnancy
  • Prenatal Exposure Delayed Effects / pathology*
  • Serotonin Uptake Inhibitors / toxicity*


  • Extracellular Matrix Proteins
  • Methylmercury Compounds
  • Parvalbumins
  • Serotonin Uptake Inhibitors
  • Fluoxetine