Setnik Beatrice, de Souza Fernanda Gonçalves, d'Almeida Vania, Nobrega José N
Neuroimaging Research Section, Centre for Addiction and Mental Health, Toronto, Canada.
Pharmacol Biochem Behav. 2004 Jan;77(1):155-61. doi: 10.1016/j.pbb.2003.10.006.
Elevated levels of homocysteine (Hcy) have been associated with major depressive (MD) illness. As human females show a higher predisposition towards depression, this study examined how Hcy levels in rats are affected by sex and estrous cycle in the learned helplessness (LH) model of depression. Male and female rats in either estrus or diestrus were subjected to LH, with intervals of 4 days between the two stress tests and between tests and sacrifice, in order to accommodate the female estrous cycle. No differences were found in LH behavior between males and females at either estrous phase. Control Hcy levels were significantly lower in females than in males (-36%, P<.001), with no further differences between estrous and diestrus phases in females. Stress exposure increased plasma Hcy by approximately 26% in females, both in estrus and diestrus, but not in males. However, when behavioral responses to stress were considered, no association was found between increased Hcy levels and propensity to develop helpless behavior. Therefore, while male rats have higher basal Hcy levels than females, females appear to be more vulnerable than males to stress-induced elevations in Hcy, although this did not correlate with behavioral responses to stress. Neither was this vulnerability influenced by estrous phase. These results imply that both stress and sex should be considered as risk factors for increased plasma Hcy.
同型半胱氨酸（Hcy）水平升高与重度抑郁症（MD）相关。由于人类女性患抑郁症的倾向更高，本研究在习得性无助（LH）抑郁模型中，研究了大鼠的Hcy水平如何受到性别和发情周期的影响。处于发情期或间情期的雄性和雌性大鼠接受LH实验，两次应激测试之间以及测试与处死之间间隔4天，以适应雌性发情周期。在任一发情阶段，雄性和雌性大鼠的LH行为均未发现差异。雌性大鼠的对照Hcy水平显著低于雄性（-36%，P<.001），雌性发情期和间情期之间没有进一步差异。应激暴露使发情期和间情期雌性大鼠的血浆Hcy水平均升高约26%，但雄性大鼠未升高。然而，当考虑对应激的行为反应时，未发现Hcy水平升高与产生无助行为的倾向之间存在关联。因此，虽然雄性大鼠的基础Hcy水平高于雌性，但雌性似乎比雄性更容易受到应激诱导的Hcy升高的影响，尽管这与对应激的行为反应无关。这种易感性也不受发情期的影响。这些结果表明，应激和性别都应被视为血浆Hcy升高的风险因素。
