Fasciculation and Elongation Protein Zeta-1 Expression in Reactive Astrocytes in a Rat Model of Frontal Lobe Injury

J Neuropathol Exp Neurol. 2020 Feb 1;79(2):194-208. doi: 10.1093/jnen/nlz113.

Abstract

There are reports that depression induced by frontal lobe injury (FLI) has a devastating effect on human mental health. We previously reported that fasciculation and elongation protein zeta-1 (FEZ1) was essential for astrocytic protection of dopamine neurons. Studies of glutamate-glutamine cycle in mental illness have been reported, whereas not from the perspective of astrocytes. This study was designed to investigate the roles of astrocytic FEZ1 and glutamate-glutamine cycle after FLI. A model of FLI was established by inserting a blade into the right frontal lobe of rats. Behavioral tests were used to observe the behavioral changes of FLI rats. Neuropathologic examinations, including immunohistochemistry, were conducted. Behavioral tests showed that FLI decreased exploratory activity. Western blot analysis revealed that the expression of astroglial proteins overall decreased in the initial injury stage, as well as FEZ1. Immunohistochemistry showed a shift of FEZ1 localization from neurons in sham-lesioned rats to astrocytes in FLI rats, and showed the expression profile of glutamate transporter 1 and glutamine synthetase (GS) was consistent with Western blot observation. Our results indicate that astrocytic FEZ1 and glutamate-glutamine cycle dysfunction may be involved in the pathogenesis of depression after FLI.

Keywords: Astrocyte; Depression; Fasciculation and elongation protein zeta-1; Frontal lobe injury; Glutamate-glutamine cycle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Amino Acid Transport System X-AG / metabolism
  • Animals
  • Astrocytes / metabolism*
  • Depression / etiology
  • Depression / metabolism*
  • Disease Models, Animal
  • Frontal Lobe / injuries*
  • Frontal Lobe / metabolism*
  • Glutamate-Ammonia Ligase / metabolism
  • Male
  • Neurons / metabolism
  • Rats, Sprague-Dawley

Substances

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Transport System X-AG
  • Fez1 protein, rat
  • Glutamate-Ammonia Ligase