The Modulation of Neurotrophin and Epigenetic Regulators: Implication for Astrocyte Proliferation and Neuronal Cell Apoptosis After Spinal Cord Injury

Abstract

OBJECTIVE: To investigate alterations in the expression of the main regulators of neuronal survival and death related to astrocytes and neuronal cells in the brain in a mouse model of spinal cord injury (SCI).

METHODS: Eight-week-old male imprinting control region mice (n=36; 30-35 g) were used in this study and randomly assigned to two groups: the na?ve control group (n=18) and SCI group (n=18). The mice in both groups were randomly allocated to the following three time points: 3 days, 1 week, and 2 weeks (n=6 each). The expression levels of regulators such as brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), nerve growth factor (NGF), histone deacetylase 1 (HDAC1), and methyl-CpG-binding protein 2 (MeCP 2) in the brain were evaluated following thoracic contusive SCI. In addition, the number of neuronal cells in the motor cortex (M1 and M2 areas) and the number of astrocytes in the hippocampus were determined by immunohistochemistry.

RESULTS: BDNF expression was significantly elevated at 2 weeks after injury (p=0.024). The GDNF level was significantly elevated at 3 days (p=0.042). The expression of HDAC1 was significantly elevated at 1 week (p=0.026). Following SCI, compared with the control the number of NeuN-positive cells in the M1 and M2 areas gradually and consistently decreased at 2 weeks after injury. In contrast, the number of astrocytes was significantly increased at 1 week (p=0.029).

CONCLUSION: These results demonstrate that the upregulation of BDNF, GDNF and HDAC1 might play on important role in brain reorganization after SCI.