N-Palmitoylethanolamide Exerts Antidepressant-Like Effects in Rats: Involvement of PPARα Pathway in the Hippocampus
N-Palmitoylethanolamide Exerts Antidepressant-Like Effects in Rats: Involvement of PPARα Pathway in the Hippocampus
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N-棕榈酰乙醇酰胺在大鼠中发挥抗抑郁样作用：海马 PPARα 通路的参与
DOI：
10.1124/jpet.118.254524
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发表时间：
2019-01
影响因子：
3.5
通讯作者：
Yu HL
中科院分区：
文献类型：
--
作者：
Li MM;Wang D;Jiang ZE;Bi WP;Piao RL;Yu HL
N-棕榈酰乙醇酰胺（PEA）是一种内源性大麻素样分子，作为内源性神经保护因子参与控制与精神障碍相关的行为。基于积累的证据和我们以前的数据，我们验证了一个假设，即PEA在慢性不可预测的轻度应激（CNOMS）中观察到的抗抑郁样作用是由过氧化物酶体增殖物激活受体α（PPARα）通路中的可能靶点介导的。在本研究中，对大鼠进行35天的PENS，并给予PEA（2.5、5.0或10 mg/kg，经口）、氟西汀（10 mg/kg，经口）或PEA和MK 886（1-[（4-氯苯基）甲基]-3-[（1，1-二甲基乙基）硫代]-α，α-二甲基-5-（1-甲基乙基）-1H-吲哚-2-丙酸）联合给药。在行为测试之后，处死动物，解剖它们的背侧肌用于后续研究。PEA使体重增加、蔗糖偏好、旷场试验中的自发活动以及海马中的PPARα mRNA和蛋白水平正常化，并降低了遭受BRAS的大鼠的血清促肾上腺皮质激素（ACTH）和皮质酮（CORT）水平。PEA逆转了几种氧化应激生物标志物的异常水平，并增加了海马中两种神经营养因子的浓度。此外，PEA减轻海马重量的下降。选择性PPARα拮抗剂MK 886可完全或部分阻断PEA的上述作用。基于这些发现，海马中的PPARα通路是PEA抗抑郁作用的可能靶点，并且在此过程中涉及稳定的下丘脑-垂体-肾上腺轴的维持、抗氧化防御和海马中神经营养因子水平的正常化。
N-Palmitoylethanolamide (PEA), an endocannabinoid-like molecule, participates in controlling behaviors associated with mental disorders as an endogenous neuroprotective factor. On the basis of accumulating evidence and our previous data, we tested the hypothesis that the antidepressant-like effects of PEA observed during chronic unpredictable mild stress (CUMS) are mediated by possible targets in the peroxisome proliferator–activated receptor alpha (PPARα) pathway. In this study, rats were subjected to 35 days of CUMS and treated with drugs such as PEA (2.5, 5.0, or 10 mg/kg, by mouth), fluoxetine (10 mg/kg, by mouth), or the combination of PEA and MK886 (1-[(4-chlorophenyl) methyl]-3-[(1,1-dimethylethyl) thio]-α,α-dimethyl-5-(1-methylethyl)-1H-indole-2-propanoic acid). After behavioral tests, the animals were sacrificed and their hippocampi were dissected for subsequent studies. PEA normalized weight gain, sucrose preferences, locomotor activity in an open-field test, and levels of the PPARα mRNA and protein in the hippocampus, and it reduced serum adrenocorticotropic hormone (ACTH) and corticosterone (CORT) levels in rats subjected to CUMS. PEA reversed the abnormal levels of several oxidative stress biomarkers and increased the concentrations of two neurotrophic factors in the hippocampus of CUMS-induced rats. In addition, PEA alleviated the decrease in hippocampal weight. However, the aforementioned effects of PEA were completely or partially abolished by MK886, a selective PPARα antagonist. On the basis of these findings, the PPARα pathway in the hippocampus is a possible target of the antidepressant effects of PEA, and the maintenance of a stable hypothalamic-pituitary-adrenal axis, the antioxidant defenses, and normalization of neurotrophic factor levels in the hippocampus are involved in this process.
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影响因子：
3.1
作者：
Halappa NG;Thirthalli J;Varambally S;Rao M;Christopher R;Nanjundaiah GB
通讯作者：
Nanjundaiah GB
影响因子：
3.3
作者：
Palta P;Samuel LJ;Miller ER 3rd;Szanton SL
通讯作者：
Szanton SL
影响因子：
6.2
作者：
Roy, Avik;Pahan, Kalipada
通讯作者：
Pahan, Kalipada
DOI：
10.12659/msm.889853
发表时间：
2014-01-24
期刊：
Medical science monitor : international medical journal of experimental and clinical research
影响因子：
--
作者：
Talarowska M;Bobińska K;Zajączkowska M;Su KP;Maes M;Gałecki P
通讯作者：
Gałecki P
影响因子：
4
作者：
Rodrigues, Roberto;Petersen, Robert B.;Perry, George
通讯作者：
Perry, George