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


CONCLUSIONS
These results demonstrate that the upregulation of BDNF, GDNF and HDAC1 might play on important role in brain reorganization after SCI.
Department of Rehabilitation Medicine, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Korea.
Jong Heon
0000-0002-7341-3231
JH
Kim
Department of Rehabilitation Medicine, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Korea.
Sung-Hoon
0000-0001-6043-7640
SH
Kim
Department of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul, Korea.
Sung-Rae
0000-0003-1429-2684
SR
Cho
Department of Rehabilitation Medicine, The Graduate School of Yonsei University Wonju College of Medicine, Wonju, Korea.
Ji Yong
0000-0002-8273-8994
JY
Lee
Department of Rehabilitation Medicine, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Korea.
Ji Hyun
0000-0001-9061-3350
JH
Kim
Department of Rehabilitation Medicine, The Graduate School of Yonsei University Wonju College of Medicine, Wonju, Korea.
Ahreum
0000-0002-9926-8482
A
Baek
Department of Rehabilitation Medicine, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Korea.
Hong Sun
0000-0002-2630-8674
HS
Jung
Astrocytes; Genes; Neurons; Regulator; Spinal cord injuries