Mild hyperhomocysteinemia is a risk factor for psychiatric and neurodegenerative diseases, whose mechanisms between them are not well-known. In the present study, we evaluated the emotional behavior and neurochemical pathways (ATPases, glutamate homeostasis, and cell viability) in amygdala and prefrontal cortex rats subjected to mild hyperhomocysteinemia (in vivo studies). The ex vivo effect of homocysteine on ATPases and redox status, as well as on NMDAR antagonism by MK-801 in same structures slices were also performed. Wistar male rats received a subcutaneous injection of 0.03 µmol Homocysteine/g of body weight or saline, twice a day from 30 to 60th–67th days of life. Hyperhomocysteinemia increased anxiety-like behavior and tended to alter locomotion/exploration of rats, whereas sucrose preference and forced swimming tests were not altered. Glutamate uptake was not changed, but the activities of glutamine synthetase and ATPases were increased. Cell viability was not altered. Ex vivo studies (slices) showed that homocysteine altered ATPases and redox status and that MK801, an NMDAR antagonist, protected amygdala (partially) and prefrontal cortex (totally) effects. Taken together, data showed that mild hyperhomocysteinemia impairs the emotional behavior, which may be associated with changes in ATPase and glutamate homeostasis, including glutamine synthetase and NMDAR overstimulation that could lead to excitotoxicity. These findings may be associated with the homocysteine risk factor on psychiatric disorders development and neurodegeneration.

轻度高同型半胱氨酸血症是精神疾病和神经退行性疾病的危险因素，它们之间的机制尚不清楚。在本研究中，我们评估了轻度高同型半胱氨酸血症（体内研究）杏仁核和前额叶皮层大鼠的情绪行为和神经化学通路（ATP 酶、谷氨酸稳态和细胞活力）。还进行了同型半胱氨酸对ATP酶和氧化还原状态的离体作用，以及MK-801在相同结构切片中对NMDAR的拮抗作用。Wistar 雄性大鼠接受皮下注射 0.03 µmol 同型半胱氨酸/g 体重或生理盐水，从生命的第 30 天到第 60 天到第 67 天，每天两次。高同型半胱氨酸血症增加焦虑样行为并倾向于改变大鼠的运动/探索，而蔗糖偏好和强迫游泳测试没有改变。谷氨酸摄取没有改变，但谷氨酰胺合成酶和ATP酶的活性增加。细胞活力没有改变。体外研究（切片）表明，同型半胱氨酸改变了 ATP 酶和氧化还原状态，并且 NMDAR 拮抗剂 MK801 保护杏仁核（部分）和前额叶皮层（完全）作用。总之，数据显示轻度高同型半胱氨酸血症会损害情绪行为，这可能与 ATP 酶和谷氨酸稳态的变化有关，包括可能导致兴奋性毒性的谷氨酰胺合成酶和 NMDAR 过度刺激。这些发现可能与精神疾病发展和神经变性的同型半胱氨酸风险因素有关。体外研究（切片）表明，同型半胱氨酸改变了 ATP 酶和氧化还原状态，并且 NMDAR 拮抗剂 MK801 保护杏仁核（部分）和前额叶皮层（完全）作用。总之，数据显示轻度高同型半胱氨酸血症会损害情绪行为，这可能与 ATP 酶和谷氨酸稳态的变化有关，包括可能导致兴奋性毒性的谷氨酰胺合成酶和 NMDAR 过度刺激。这些发现可能与精神疾病发展和神经变性的同型半胱氨酸风险因素有关。体外研究（切片）表明，同型半胱氨酸改变了 ATP 酶和氧化还原状态，并且 NMDAR 拮抗剂 MK801 保护杏仁核（部分）和前额叶皮层（完全）作用。总之，数据显示轻度高同型半胱氨酸血症会损害情绪行为，这可能与 ATP 酶和谷氨酸稳态的变化有关，包括可能导致兴奋性毒性的谷氨酰胺合成酶和 NMDAR 过度刺激。这些发现可能与精神疾病发展和神经变性的同型半胱氨酸风险因素有关。这可能与 ATP 酶和谷氨酸稳态的变化有关，包括可能导致兴奋性毒性的谷氨酰胺合成酶和 NMDAR 过度刺激。这些发现可能与精神疾病发展和神经变性的同型半胱氨酸风险因素有关。这可能与 ATP 酶和谷氨酸稳态的变化有关，包括可能导致兴奋性毒性的谷氨酰胺合成酶和 NMDAR 过度刺激。这些发现可能与精神疾病发展和神经变性的同型半胱氨酸风险因素有关。