在成年大鼠中，早期母亲分离增强了后来社会隔离通过氧化应激诱导抑郁样行为的影响。

IF 3.5 3区医学 Q2 NEUROSCIENCES

Psychopharmacology Pub Date : 2025-05-20 DOI:10.1007/s00213-025-06811-0

Yating Chen, Jingjing Du, Mengzhu Lei, Na Ji, Wei Zhang, Chuanyu Li, Bo Zhang

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引用次数: 0

摘要

理论基础：经历过早期生活压力（ELS）的个体更容易受到晚年生活压力诱发的抑郁症的影响，这可能归因于ELS对晚年生活压力的增强影响。这一假设和涉及的神经生物学机制需要进一步的验证和阐明。目的：探讨断奶前母亲分离（MS）对断奶后社会隔离（SI）诱导抑郁样行为的影响，以及中枢性氧化应激、谷氨酸能和脑源性神经营养因子(BDNF)/酪氨酸激酶受体B （TrkB）信号在这一过程中的作用。方法：将雄性子代分别暴露于MS、SI和母亲分离与社会隔离（MSSI）压力下。在青少年或成人行为测试前，受试者分别接受生理盐水、抗氧化剂二烯丙基二硫醚（DADS）（30 mg/kg, ig）或抗抑郁药氟西汀（10 mg/kg, ig）治疗两周。抑郁样行为通过蔗糖偏好、强迫游泳和悬尾试验进行评估。采用免疫印迹法检测海马和血清中4-羟基壬烯醛（4-HNE）、谷胱甘肽、超氧化物歧化酶的浓度，以及海马谷氨酸转运蛋白1 （GLT-1）、BDNF、TrkB蛋白的表达。结果：在成人中，MSSI，而不是MS或SI，诱发了显著的抑郁样行为，但在青少年中没有。与此一致的是，只有MSSI显著升高了4-HNE，而抑制了成人海马的GLT-1、BDNF和TrkB。msi诱导的成人行为和生化异常可通过DADS或氟西汀治疗逆转。结论：早期MS通过提高氧化应激和中断大脑中的谷氨酸能和BDNF/TrkB信号，以年龄依赖性增强了后期SI对雄性大鼠诱导抑郁样行为的影响。结果进一步表明抗氧化治疗是一种有前景的抗抑郁途径。

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Early maternal separation potentiates the impact of later social isolation in inducing depressive-like behavior via oxidative stress in adult rats.

Rationale: Individuals who have experienced early life stress (ELS) are more vulnerable to later life stress induced depression, which might attribute to ELS potentiated impact of later life stress. The presumption and neurobiological mechanisms involved require further validation and elucidation.

Objectives: To investigate impact of pre-weaning maternal separation (MS) on post-weaning social isolation (SI) in inducing depressive-like behavior, and involvement of central oxidative stress, glutamatergic and brain-derived neurotrophic factor (BDNF)/tyrosine kinase receptor B (TrkB) signaling in the process.

Methods: Male offspring were exposed to MS, SI or maternal separation and social isolation (MSSI) stress, respectively. Subjects were treated with saline, antioxidant diallyl disulfide (DADS) (30 mg/kg, i.g.) or antidepressant fluoxetine (10 mg/kg, i.p.), for two weeks before behavioral tests in adolescents or adults. Depressive-like behavior was assessed with sucrose preference, forced swim and tail suspension tests. Concentrations of 4-hydroxynonenal (4-HNE), glutathione and superoxide dismutase in hippocampus and serum, and hippocampal protein expressions of glutamate transporter 1 (GLT-1), BDNF and TrkB were assessed by western blotting analysis.

Results: MSSI, rather than MS or SI, induced significant depressive-like behavior, in adults but not adolescents. Consistently, only MSSI significantly elevated 4-HNE, whereas inhibited GLT-1, BDNF and TrkB in adult hippocampus. MSSI induced behavioral and biochemical abnormalities in adults were reversed by DADS or fluoxetine treatment.

Conclusions: Early MS age-dependently potentiates later SI impact in inducing depressive-like behavior in male rats, through elevating oxidative stress and interrupting glutamatergic and BDNF/TrkB signaling in the brain. Results further suggest antioxidant treatment as a promising anti-depressant avenue.

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来源期刊

Psychopharmacology 医学-精神病学

CiteScore

7.10

自引率

5.90%

发文量

257

审稿时长

2-4 weeks

期刊介绍： Official Journal of the European Behavioural Pharmacology Society (EBPS) Psychopharmacology is an international journal that covers the broad topic of elucidating mechanisms by which drugs affect behavior. The scope of the journal encompasses the following fields: Human Psychopharmacology: Experimental This section includes manuscripts describing the effects of drugs on mood, behavior, cognition and physiology in humans. The journal encourages submissions that involve brain imaging, genetics, neuroendocrinology, and developmental topics. Usually manuscripts in this section describe studies conducted under controlled conditions, but occasionally descriptive or observational studies are also considered. Human Psychopharmacology: Clinical and Translational This section comprises studies addressing the broad intersection of drugs and psychiatric illness. This includes not only clinical trials and studies of drug usage and metabolism, drug surveillance, and pharmacoepidemiology, but also work utilizing the entire range of clinically relevant methodologies, including neuroimaging, pharmacogenetics, cognitive science, biomarkers, and others. Work directed toward the translation of preclinical to clinical knowledge is especially encouraged. The key feature of submissions to this section is that they involve a focus on clinical aspects. Preclinical psychopharmacology: Behavioral and Neural This section considers reports on the effects of compounds with defined chemical structures on any aspect of behavior, in particular when correlated with neurochemical effects, in species other than humans. Manuscripts containing neuroscientific techniques in combination with behavior are welcome. We encourage reports of studies that provide insight into the mechanisms of drug action, at the behavioral and molecular levels. Preclinical Psychopharmacology: Translational This section considers manuscripts that enhance the confidence in a central mechanism that could be of therapeutic value for psychiatric or neurological patients, using disease-relevant preclinical models and tests, or that report on preclinical manipulations and challenges that have the potential to be translated to the clinic. Studies aiming at the refinement of preclinical models based upon clinical findings (back-translation) will also be considered. The journal particularly encourages submissions that integrate measures of target tissue exposure, activity on the molecular target and/or modulation of the targeted biochemical pathways. Preclinical Psychopharmacology: Molecular, Genetic and Epigenetic This section focuses on the molecular and cellular actions of neuropharmacological agents / drugs, and the identification / validation of drug targets affecting the CNS in health and disease. We particularly encourage studies that provide insight into the mechanisms of drug action at the molecular level. Manuscripts containing evidence for genetic or epigenetic effects on neurochemistry or behavior are welcome.