Nꭃ-nitro-l-arginine methyl model of pre-eclampsia elicits differential IBA1 and EAAT1 expressions in brain

J Chem Neuroanat. 2019 Oct:100:101660. doi: 10.1016/j.jchemneu.2019.101660. Epub 2019 Jun 25.

Abstract

Pre-eclampsia (PE) is a pregnancy syndrome associated with an increased risk of both the mother and the baby developing cardiovascular disorders later in life. It is widely accepted that women with severe PE develop a neurological impairment however studies have revealed that the mother and baby are at jeopardy for a neurological deficit later in life. The present study examined expression of Ionized calcium binding adaptor molecule 1 (IBA1) and Excitatory amino acid transporter 1 (EAAT1) as neuroinflammatory markers in an Nꭃ-nitro-l-arginine methyl (L-NAME) model of early- and late-onset (EOPE/ LOPE) PE-like syndrome in rat models. Forty-five adult nulliparous pregnant Sprague-Dawley rats were used for this experiment. They were divided into Control, EOPE and LOPE groups. Administration of L-Name was done between gestational days 8-17 for the treated groups. Animals were sacrificed at gestational day (GD) 19, post-natal day (PND) 1 and 60 and the brain excised for further analysis. Our study confirmed L-NAME induced PE-like symptoms in rat models as evidenced by significant increase in systolic blood pressure and urine protein compared with Control. There was upregulation of IBA1 expression and increased microglial activation in the brain of PE rat models assessed at gestational day 19, post-natal day 1 and 60. Also, IBA1 expression is up regulated in the pups at post-natal day 1 and 60. Contrastingly, EAAT1 expression is down-regulated in the brain of PE rat models assessed at gestational day 19, post-natal day 1 and 60, as well as offspring at post-natal day 1 and 60. These results demonstrate likely neuro-inflammation within the brain of PE mothers during pregnancy, that persist into later life, as well as possible neuro-inflammation in brains of offspring of PE mothers.

Keywords: (L)-NAME; EAAT1; IBA1; Neuro-inflammation; Offspring; PE mothers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / metabolism*
  • Brain / pathology
  • Calcium-Binding Proteins / metabolism*
  • Disease Models, Animal
  • Excitatory Amino Acid Transporter 1 / metabolism*
  • Female
  • Inflammation / etiology
  • Inflammation / metabolism
  • Inflammation / pathology
  • Microfilament Proteins / metabolism*
  • NG-Nitroarginine Methyl Ester / toxicity
  • Pre-Eclampsia / chemically induced
  • Pre-Eclampsia / metabolism*
  • Pre-Eclampsia / pathology
  • Pregnancy
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Aif1 protein, rat
  • Calcium-Binding Proteins
  • Excitatory Amino Acid Transporter 1
  • Microfilament Proteins
  • Slc1a3 protein, rat
  • NG-Nitroarginine Methyl Ester