School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, China.
Beijing University of Chinese Medicine, Beijing, 100029, China.
BMC Psychiatry. 2018 Oct 17;18(1):337. doi: 10.1186/s12888-018-1880-y.
The etiology of depression and its effective therapeutic treatment have not been clearly identified. Using behavioral phenotyping and resting-state functional magnetic resonance imaging (r-fMRI), we investigated the behavioral impact and cerebral alterations of chronic unpredictable mild stress (CUMS) in the rat. We also evaluated the efficacy of telmisartan therapy in this rodent model of depression.
Thirty-two rats were divided into 4 groups: a control group(C group), a stress group(S group), a stress + telmisartan(0.5 mg/kg)group (T-0.5 mg/kg group) and a stress + telmisartan(1 mg/kg) group (T-1 mg/kg group). A behavioral battery, including an open field test (OFT), a sucrose preference test (SPT), and an object recognition test (ORT), as well as r-fMRI were conducted after 4 weeks of CUMS and telmisartan therapy. The r-fMRI data were analyzed using the amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) approach. The group differences in the behavior and r-fMRI test results as well as the correlations between these 2 approaches were examined.
CUMS reduced the number of rearings and the total moved distance in OFT, the sucrose preference in SPT, and novel object recognition ability in ORT. The telmisartan treatment (1 mg/kg) significantly improved B-A/B + A in the ORT and improved latency scores in the OFT and SPT. The S group exhibited a decreased ReHo in the motor cortex and pons, but increased ReHo in the thalamus, visual cortex, midbrain, cerebellum, hippocampus, hypothalamus, and olfactory cortex compared to the C group. Telmisartan (1 mg/kg)reversed or attenuated the stress-induced changes in the motor cortex, midbrain, thalamus, hippocampus, hypothalamus, visual cortex, and olfactory cortex. A negative correlation was found between OFT rearing and ReHo values in the thalamus. Two positive correlations were found between ORT B-A and the ReHo values in the olfactory cortexand pons.
Telmisartan may be an effective complementary drug for individuals with depression who also exhibit memory impairments. Stress induced widespread regional alterations in the cerebrum in ReHo measures while telmissartan can reverse part of theses alterations. These data lend support for future research on the pathology of depression and provide a new insight into the effects of telmisartan on brain function in depression.
抑郁症的病因及其有效治疗方法尚未明确。本研究采用行为表型和静息态功能磁共振成像（r-fMRI）技术，观察慢性不可预测轻度应激（CUMS）对大鼠的行为影响和脑区改变，并评估替米沙坦治疗该抑郁模型的疗效。
32 只大鼠随机分为 4 组：对照组（C 组）、应激组（S 组）、应激+替米沙坦（0.5mg/kg）组（T-0.5mg/kg 组）和应激+替米沙坦（1mg/kg）组（T-1mg/kg 组）。经过 4 周 CUMS 和替米沙坦治疗后，进行行为学测试（旷场实验、糖水偏好实验、物体识别实验）和 r-fMRI 检查。r-fMRI 数据采用低频振幅（ALFF）和局部一致性（ReHo）分析方法进行分析。比较各组行为学和 r-fMRI 结果的差异，并分析两者之间的相关性。
CUMS 降低了旷场实验中的后肢站立次数和总运动距离、糖水偏好实验中的糖水偏好率以及物体识别实验中的新物体识别能力。替米沙坦（1mg/kg）治疗显著提高了物体识别实验中的 B-A/B+A 比值，并改善了旷场实验和糖水偏好实验中的潜伏期评分。与 C 组相比，S 组运动皮质和脑桥的 ReHo 值降低，而丘脑、视皮质、中脑、小脑、海马、下丘脑和嗅皮质的 ReHo 值升高。替米沙坦（1mg/kg）治疗逆转或减轻了 CUMS 引起的运动皮质、中脑、丘脑、海马、下丘脑、视皮质和嗅皮质的变化。旷场实验中的后肢站立次数与丘脑的 ReHo 值呈负相关，物体识别实验中的 B-A 与嗅皮质和脑桥的 ReHo 值呈正相关。
替米沙坦可能是一种有效的补充药物，可用于治疗伴有记忆障碍的抑郁症患者。应激导致大脑在 ReHo 测量中广泛区域改变，而替米沙坦可以逆转其中的部分改变。这些数据为进一步研究抑郁症的发病机制提供了支持，并为替米沙坦治疗抑郁症的脑功能提供了新的见解。
