Up-regulation of FoxN4 Expression in Adult Spinal Cord After Injury

Xiangdong Chen,Feng Zhang,Junjie Guan,Yu Yao,Xiaoqing Chen

doi:10.1007/s12031-013-0166-6

Xiangdong Chen, Feng Zhang + Show 3 more

Open Access

https://doi.org/10.1007/s12031-013-0166-6

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Abstract

FoxN4 (forkhead box N4), which is a transcription factor involved in developing spinal cord and spinal neurogenesis, implied important roles in the central nervous system (CNS). However, its expression and function in the adult CNS lesion are still unclear. In this study, we established a spinal cord injury (SCI) model in adult rats and investigated the expression of FoxN4 in the spinal cord. Western blot analysis revealed that FoxN4 was present in normal spinal cord. It gradually increased, peaked at day 3 after SCI, and then decreased during the following days. Immunohistochemistry further confirmed that FoxN4 was expressed at low levels in gray and white matters in normal condition and increased after SCI. Double immunofluorescence staining showed that FoxN4 is located on neurons and astrocytes, and FoxN4 expression was increased progressively in reactive astrocytes within the vicinity of the lesion, predominately in the white matter. In addition, almost all FoxN4-positive cells also expressed nestin or PCNA. Our data suggested that FoxN4 might play important roles in CNS pathophysiology after SCI.

Highlights

Spinal cord injury (SCI) is a common neurological disorder that causes death in children and adults and results in a significant society burden all over the world (Sekhon and Fehlings 2001; McDonald and Sadowsky 2002)
Astrocytes are the main cell type involved in spinal cord injury and becoming reactive and increasing in size that lead to a reactive phenotype capable of mediating wound healing following central nervous system injury (Wu et al 2012; Yin et al 2012)
After SCI, reactive astrocytes appear as strong expression of intermediate filaments, such as GFAP and nestin (Eng 1985)

Summary

Introduction

Spinal cord injury (SCI) is a common neurological disorder that causes death in children and adults and results in a significant society burden all over the world (Sekhon and Fehlings 2001; McDonald and Sadowsky 2002). The forkhead/winged helix family is a large family of transcriptional regulators, which involved in a wide range of biological processes, such as proliferation, apoptosis, development, differentiation, migration, and invasion (Laoukili et al 2005; Koo, Muir and Lam 2012) Among these characteristics, forkhead family seems important in cell differentiation, developmental processes, and neurogenesis in the CNS (Filosa et al 1997; Labosky et al 1997; Herrera et al 2004; Vargha-Khadem et al 2005), such as FoxJ1, which is required for activating a subset of astrocytes that participate in neurogenesis and gliogenesis in spinal cord injury and in response to stroke (Jacquet et al 2009; Meletis et al 2008; Carlen et al 2009). After incubating with an anti-mouse or anti-rabbit horseradish peroxidaseconjugated secondary antibody, protein was visualized by enhanced chemiluminescence system (ECL, Pierce Company, USA)

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