IMR Press / JIN / Volume 20 / Issue 3 / DOI: 10.31083/j.jin2003067
Open Access Original Research
Changes in depressive-like behaviors induced by spinal cord injury based on the hypothalamic-pituitary-adrenal axis and hippocampal neurogenesis
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1 School of Nursing, Jilin University, 130021 Changchun, Jilin, China
2 School of Nursing, Dalian University, 116622 Dalian, Liaoning, China
*Correspondence: (Li-Bin An)
These authors contributed equally.
J. Integr. Neurosci. 2021, 20(3), 635–644;
Submitted: 30 May 2021 | Revised: 22 June 2021 | Accepted: 9 August 2021 | Published: 30 September 2021
Copyright: © 2021 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license (

A reduction in sucrose preference is a key characteristic of depressive-like behaviors after spinal cord injury as judged by the sucrose preference test, the hypothalamic-pituitary-adrenal axis and adult hippocampal neurogenesis. Male rats were divided into three groups: control, sham and spinal cord injury groups. The spinal cord injury rats received a severe mid-thoracic contusion. The Basso, Beattie and Bresnahan score was used to assess motor function. The sucrose preference test and forced swim test were used to evaluate depressive-like behaviors. Serum corticosterone levels were examined by enzyme-linked immunosorbent assay and hippocampal glucocorticoid receptor levels were examined by Western blot to evaluate the function of the hypothalamic-pituitary-adrenal axis. Adult hippocampal neurogenesis was assessed by testing hippocampal brain-derived neurotrophic factor and tropomyosin receptor kinase B levels by Western blot and doublecortin levels by immunohistochemistry. Data showed that spinal cord injury impaired motor function. The spinal cord injury rats exhibited decreased sucrose preference on day six, which continued to decrease until day twelve, followed by a plateau phase. Additionally, the immobility time of the spinal cord injury rats was increased on day thirty-four. Moreover, serum corticosterone levels in the spinal cord injury group peaked on day seven, was decreased by day twenty-one and was increased again on day thirty-five. Serum corticosterone levels were significantly negatively correlated with sucrose preference and positively correlated with immobility time. Finally, hippocampal doublecortin levels on days twenty-one and thirty-five were lower in the spinal cord injury group than in the other groups. These results suggest that hyperactivation of the hypothalamic-pituitary-adrenal axis and the inhibition of adult hippocampal neurogenesis may be part of the underlying mechanism responsible for depressive-like behaviors after spinal cord injury.

Spinal cord injury
Depressive-like behaviors
Hypothalamic-pituitary-adrenal axis
Adult hippocampal neurogenesis
Sucrose test
Fig. 1.
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