To date, our results provide the only evidence showing the existence of FEZ1 in striatum and substantia nigra of adult rat brain, an elevation of FEZ1 gene and protein levels

after 6-OHDA injection, and the cellular localization of FEZ1 in striatum and substantia nigra of both 6-OHDA-lesioned and sham-lesioned rats. Navitoclax Additionally, our data showed that FEZ1 mRNA and protein expression in striatum and substantia nigra gradually increased after injury, peaked, and then decreased. It has been previously described that FEZ1 is associated with dopaminergic neurone differentiation [30], and furthermore, another study has shown that FEZ1-deficient mice often present with abnormal behaviours resulting from altered dopamine release in the mesolimbic pathway [32]. Colocalization of FEZ1 within GFAP-positive click here or TH-positive cells demonstrated that FEZ1 was predominantly expressed by TH-positive neurones in sham-operated rats. In contrast, FEZ1 colocalized with GFAP-positive cells in PD rats, demonstrating the exclusive expression of FEZ1 in reactive astrocytes. Altogether, the preservation of FEZ1 mRNA levels in PD rats likely reflects a dynamic shift of expression from dopaminergic neurones to astrocytes during disease-associated

tissue remodelling. Sakae et al. indicated that a FEZ1 deficiency in GABAergic neurones may alter dopaminergic transmission, resulting in abnormal behaviours. They suggested that FEZ1 in GABAergic neurones might be neuroprotective [32]. In our observations,

FEZ1 levels in astrocytes increased in substantia nigra of PD rats, suggesting that astrocytic FEZ1 also plays an important role in neuroprotection. In cultured hippocampal neurones, the silencing of FEZ1 by FEZ1 siRNA inhibits axonal elongation [24]. Therefore, the loss of FEZ1 in TH-positive neurones may lead to the degeneration of dopamine Coproporphyrinogen III oxidase neurones. We supposed that injury to DA neurones might increase astrocytic FEZ1 levels in substantia nigra, knowing that the participation of reactive astrocytes in PD pathogenesis was generally assumed. Thus, we hypothesized that FEZ1 might be critical for astrocyte activation after injury. Our triple immunostaining detection of TH, GFAP and FEZ1 further confirmed our hypothesis. In addition, Western blot analysis showed that in striatum and substantia nigra after injury, there was a remarkable increase in GFAP expression levels. It is therefore possible that a direct link between FEZ1 expression and reactive astrocytes exists after injury. We examined the cortex and did not find changes in FEZ1 in neurones or astrocytes (data not shown). We believe that relocalization of FEZ1 into astrocytes might be caused by the damage to DA neurones, which induces an upregulation of FEZ1 in astrocytes. Taken together, these data indicate that a relationship exists between FEZ1 expression and reactive gliosis following 6-OHDA-induced injury.