Fasciculation and elongation protein zeta-1 (FEZ1) expression in reactive astrocytes in a rat model of Parkinson's disease

Neuropathol Appl Neurobiol. 2014 Feb;40(2):164-76. doi: 10.1111/nan.12077.

Abstract

Aims: Fasciculation and elongation protein zeta-1 (FEZ1) is a critical regulator of dopaminergic neurone differentiation and dopamine release. However, to date, few studies evaluating the expression patterns of FEZ1 in Parkinson's disease (PD) have been reported. The aim of this study was to investigate the expression and cellular localization of FEZ1 in a rat model of PD and to explore the role of FEZ1 in PD pathogenesis.

Methods: Male Sprague-Dawley rats were randomly divided into two groups: a PD group and a sham group. A model of PD was established by injecting 6-Hydroxydopamine Hydrobromide (6-OHDA) into the right medial forebrain bundle of rats. Sham-lesioned rats were infused with equivalent amounts of saline and served as controls. The expression levels of FEZ1 mRNA and protein in striatum and substantia nigra were examined by real-time polymerase chain reaction (PCR) and by Western blot analysis respectively. Immunohistochemistry was performed to identify the cellular localization of FEZ1 in sham-lesioned and PD rats.

Results: Western blot and real-time PCR analyses demonstrated that FEZ1 was present in normal rat brain striatum and substantia nigra. After the 6-OHDA injection, FEZ1 expression gradually increased, peaked and then decreased. Immunohistochemical detection showed a shift of FEZ1 expression from tyrosine hydroxylase positive neurones in sham-lesioned rats to astrocytes in PD rats.

Conclusions: Our results indicate that FEZ1 plays a role in the astrocytic protection of dopamine neurones and in the regulation of the neuronal microenvironment during the progression of PD.

Keywords: Parkinson's disease; astrocytes; dopaminergic neurone; fasciculation and elongation protein zeta-1; rat; tyrosine hydroxylase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Astrocytes / metabolism*
  • Corpus Striatum / metabolism*
  • Disease Models, Animal
  • Male
  • Motor Activity / drug effects
  • Parkinsonian Disorders / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Substantia Nigra / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Fez1 protein, rat