Hyperhomocysteinemia is a result, rather than a cause, of depression under chronic stress
Shen Chengfeng1, Liu Wei2, Wang Xinxing3
1Tianjin Centers for Disease Control and Prevention, Tianjin, China.
Insights
Elevated homocysteine (Hcy) levels do not cause depression in rats subjected to chronic stress. Instead, increased Hcy appears to be a consequence of stress-induced depression.
Area of Science:
- Neuroscience
- Biochemistry
Background:
- Homocysteine (Hcy) accumulation is linked to depression pathogenesis.
- The direct role of Hcy as a primary cause of depressive symptoms is not fully understood.
Purpose of the Study:
- To investigate if elevated homocysteine (Hcy) plays a significant role in stress-induced depression.
Main Methods:
- Utilized the chronic unpredictable mild stress (CUMS) model in Wistar rats for 8 weeks.
- Assessed depression-like behaviors (anhedonia) and hippocampal 5-Hydroxy Tryptophan (5-HT) levels.
- Monitored plasma Hcy levels, and the effects of sertraline and RhBHMT.
Main Results:
- CUMS rats exhibited depression-like symptoms and increased hippocampal 5-HT reduction after 4 weeks.
- Plasma Hcy levels increased in CUMS rats by 8 weeks.
- Sertraline reduced plasma Hcy and improved depressive symptoms; RhBHMT reduced Hcy but not depressive symptoms.
Conclusions:
- Findings do not support the hypothesis that increased Hcy mediates stress-induced depression.
- Elevated plasma Hcy in CUMS rats is likely a result of depression, not its cause.
Background:
Although the accumulation of homocysteine (Hcy) has been implicated in the pathogenesis of depression, whether Hcy is directly involved and acts as the primary cause of depressive symptoms remains unclear. The present study was designed to clarify whether increased Hcy plays an important role in stress-induced depression.
Results:
We employed the chronic unpredictable mild stress model (CUMS) of depression for 8 weeks to observe changes in the plasma Hcy level in the development of depression. The results showed that Wistar rats exposed to a series of mild, unpredictable stressors for 4 weeks displayed depression-like symptoms such as anhedonia (decreased sucrose preferences) and a decreased 5-Hydroxy Tryptophan (5-HT) concentration in the hippocampus. At the end of 8 weeks, the plasma Hcy level increased in the CUMS rats. The anti-depressant sertraline could decrease the plasma Hcy level and improve the depression-like symptoms in the CUMS rats. RhBHMT, an Hcy metabolic enzyme, could decrease the plasma Hcy level significantly, although it could not improve the depressive symptoms in the CUMS rats.
Conclusions:
The results obtained from the experiments did not support the hypothesis that the increased Hcy concentration mediated the provocation of depression in CUMS rats, and the findings suggested that the increased Hcy concentration in the plasma might be the result of stress-induced depression.
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