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已发表论文
亚麻籽补充通过大鼠腹侧被盖区GDNF表观遗传调控增强对应激诱导抑郁样行为的韧性
Authors Lu Q, Chen X, Zhou X, Zhang R, Deng X, Zhu X, Zhang Y
Received 14 September 2025
Accepted for publication 7 January 2026
Published 20 January 2026 Volume 2026:22 562758
DOI https://doi.org/10.2147/NDT.S562758
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Dr Roger Pinder
Qing Lu,1,2,* Xinyu Chen,1,2,* Xiao Zhou,1,2 Ruoyi Zhang,1,2 Xin Deng,3 Xiongzhao Zhu,1,2,4,5 Yi Zhang1,2,4,5
1Medical Psychological Center, The Second Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 2Medical Psychological Institute of Central South University, Changsha, People’s Republic of China; 3Institute of Bast Fiber Crops, Chinese Academy of Agricultural Sciences, Changsha, Hunan, People’s Republic of China; 4National Clinical Research Center on Mental Disorders (Xiangya), Changsha, People’s Republic of China; 5National Center for Mental Disorder, Changsha, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Yi Zhang, Medical Psychological Center, The Second Xiangya Hospital, Central South University, 139 Renmin Road, Changsha, Hunan, 410011, People’s Republic of China, Email zhangyipsy@csu.edu.cn Xiongzhao Zhu, Medical Psychological Center, The Second Xiangya Hospital, Central South University, 139 Renmin Road, Changsha, Hunan, 410011, People’s Republic of China, Email xiongzhaozhu@csu.edu.cn
Objective: To study the improvement of dietary flaxseed supplementation on resilience to chronic stress-induced depression-like behaviors of rats and investigate whether these behavioral effects are associated with alterations in glial cell line–derived neurotrophic factor (GDNF) promoter methylation and expression in the ventral tegmental area (VTA).
Methods: Forty-eight male rats were randomly grouped to chronic unpredictable stress (CUS) alone, or with flaxseeds oil (CUS/FO), or flaxseed flour (CUS/FF), flaxseed oil alone (FO), flaxseed flour alone (FF), or not any treatments (blank control, BC). FO, FF, CUS/FO, CUS/FF rats treated flaxseeds oil or flour for 5 weeks. During the second week of the 5-week period, CUS, CUS/FO, CUS/FL rats were subjected to chronic unpredictable stress for 4 weeks. Sucrose preference test (SPT) and forced swim test (FST) were used to rats’ behavioral performance. The methylation levels, mRNA and protein expression of GDNF gene in the VTA were also measured after behavioral test.
Results: CUS/FO rats exhibited a significantly higher sucrose preference rate (SPR) in the SPT than CUS rats (p< 0.05). CUS/FO and CUS/FF rats both exhibited significantly shorter immobility time, longer climbing and swimming time in the FST than CUS rats (ps< 0.05). FO rats also showed a significantly increased SPR compared with BC (p< 0.05). Both GDNF protein and mRNA level in CUS/FO rats were significantly higher compared with CUS alone (ps< 0.05). There was significantly lower GDNF gene promotor methylation in CUS/FO, CUS/FF compared with CUS alone (ps< 0.05).
Conclusion: Flaxseed supplementation, particularly flaxseed oil, confers resilience to chronic stress and attenuates depression-like behaviors in rat. In addition, enhancing hedonic capacity may be a key mechanism by which flaxseed promotes resilience to stress. These behavioral improvements may be mediated, at least in part, by decreased methylation of the GDNF gene promoter and subsequently up-regulation of GDNF gene expression in the VTA, highlighting an epigenetic mechanism linking dietary interventions to stress-related behavioral outcomes.
Keywords: flaxseed, stress resilience, depression, GDNF, ventral tegmental area, rat
1Medical Psychological Center, The Second Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 2Medical Psychological Institute of Central South University, Changsha, People’s Republic of China; 3Institute of Bast Fiber Crops, Chinese Academy of Agricultural Sciences, Changsha, Hunan, People’s Republic of China; 4National Clinical Research Center on Mental Disorders (Xiangya), Changsha, People’s Republic of China; 5National Center for Mental Disorder, Changsha, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Yi Zhang, Medical Psychological Center, The Second Xiangya Hospital, Central South University, 139 Renmin Road, Changsha, Hunan, 410011, People’s Republic of China, Email zhangyipsy@csu.edu.cn Xiongzhao Zhu, Medical Psychological Center, The Second Xiangya Hospital, Central South University, 139 Renmin Road, Changsha, Hunan, 410011, People’s Republic of China, Email xiongzhaozhu@csu.edu.cn
Objective: To study the improvement of dietary flaxseed supplementation on resilience to chronic stress-induced depression-like behaviors of rats and investigate whether these behavioral effects are associated with alterations in glial cell line–derived neurotrophic factor (GDNF) promoter methylation and expression in the ventral tegmental area (VTA).
Methods: Forty-eight male rats were randomly grouped to chronic unpredictable stress (CUS) alone, or with flaxseeds oil (CUS/FO), or flaxseed flour (CUS/FF), flaxseed oil alone (FO), flaxseed flour alone (FF), or not any treatments (blank control, BC). FO, FF, CUS/FO, CUS/FF rats treated flaxseeds oil or flour for 5 weeks. During the second week of the 5-week period, CUS, CUS/FO, CUS/FL rats were subjected to chronic unpredictable stress for 4 weeks. Sucrose preference test (SPT) and forced swim test (FST) were used to rats’ behavioral performance. The methylation levels, mRNA and protein expression of GDNF gene in the VTA were also measured after behavioral test.
Results: CUS/FO rats exhibited a significantly higher sucrose preference rate (SPR) in the SPT than CUS rats (p< 0.05). CUS/FO and CUS/FF rats both exhibited significantly shorter immobility time, longer climbing and swimming time in the FST than CUS rats (ps< 0.05). FO rats also showed a significantly increased SPR compared with BC (p< 0.05). Both GDNF protein and mRNA level in CUS/FO rats were significantly higher compared with CUS alone (ps< 0.05). There was significantly lower GDNF gene promotor methylation in CUS/FO, CUS/FF compared with CUS alone (ps< 0.05).
Conclusion: Flaxseed supplementation, particularly flaxseed oil, confers resilience to chronic stress and attenuates depression-like behaviors in rat. In addition, enhancing hedonic capacity may be a key mechanism by which flaxseed promotes resilience to stress. These behavioral improvements may be mediated, at least in part, by decreased methylation of the GDNF gene promoter and subsequently up-regulation of GDNF gene expression in the VTA, highlighting an epigenetic mechanism linking dietary interventions to stress-related behavioral outcomes.
Keywords: flaxseed, stress resilience, depression, GDNF, ventral tegmental area, rat