Early life stress lastingly alters the function and AMPA-receptor composition of glutamatergic synapses in the hippocampus of male mice

IF 3.3 4区 医学 Q2 ENDOCRINOLOGY & METABOLISM
Niek Brosens, Carla Simon, Helmut W. Kessels, Paul J. Lucassen, Harm J. Krugers
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Abstract

Early postnatal life is a sensitive period of development that shapes brain structure and function later in life. Exposure to stress during this critical time window can alter brain development and may enhance the susceptibility to psychopathology and neurodegenerative disorders later in life. The developmental effects of early life stress (ELS) on synaptic function are not fully understood, but could provide mechanistic insights into how ELS modifies later brain function and disease risk. We here assessed the effects of ELS on synaptic function and composition in the hippocampus of male mice. Mice were subjected to ELS by housing dams and pups with limited bedding and nesting material from postnatal days (P) 2–9. Synaptic strength was measured in terms of miniature excitatory postsynaptic currents (mEPSCs) in the hippocampal dentate gyrus at three different developmental stages: the early postnatal phase (P9), preadolescence (P21, at weaning) and adulthood at 3 months of age (3MO). Hippocampal synaptosome fractions were isolated from P9 and 3MO tissue and analyzed for protein content to assess postsynaptic composition. Finally, dendritic spine density was assessed in the DG at 3MO. At P9, ELS increased mEPSC frequency and amplitude. In parallel, synaptic composition was altered as PSD-95, GluA3 and GluN2B content were significantly decreased. The increased mEPSC frequency was sustained up to 3MO, at which age, GluA3 content was significantly increased. No differences were found in dendritic spine density. These findings highlight how ELS affects the development of hippocampal synapses, which could provide valuable insight into mechanisms how ELS alters brain function later in life.

Abstract Image

早期生活压力会持久改变雄性小鼠海马谷氨酸能突触的功能和AMPA受体组成。
出生后早期是一个敏感的发育时期,它塑造了以后的大脑结构和功能。在这个关键的时间窗口暴露在压力下会改变大脑发育,并可能增加日后患精神病理学和神经退行性疾病的易感性。早期生活压力(ELS)对突触功能的发育影响尚不完全清楚,但可能为ELS如何改变后期大脑功能和疾病风险提供机制见解。我们在此评估了ELS对雄性小鼠海马突触功能和组成的影响。从出生后第2-9天起,通过用有限的寝具和筑巢材料饲养母鼠和幼崽来对小鼠进行ELS(P)。突触强度是根据海马齿状回在三个不同发育阶段的微型兴奋性突触后电流(mEPSC)来测量的:出生后早期(P9)、青春期前(P21,断奶时)和3岁成年 月龄(3MO)。从P9和3MO组织中分离海马突触体部分,并分析蛋白质含量以评估突触后组成。最后,在3MO的DG中评估树突棘密度。在P9,ELS增加了mEPSC的频率和振幅。同时,突触组成发生改变,PSD-95、GluA3和GluN2B含量显著降低。mEPSC频率的增加一直持续到3MO,在这个年龄,GluA3含量显著增加。树突棘密度没有发现差异。这些发现突出了ELS如何影响海马突触的发育,这可能为深入了解ELS如何在晚年改变大脑功能的机制提供有价值的见解。
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来源期刊
Journal of Neuroendocrinology
Journal of Neuroendocrinology 医学-内分泌学与代谢
CiteScore
6.40
自引率
6.20%
发文量
137
审稿时长
4-8 weeks
期刊介绍: Journal of Neuroendocrinology provides the principal international focus for the newest ideas in classical neuroendocrinology and its expanding interface with the regulation of behavioural, cognitive, developmental, degenerative and metabolic processes. Through the rapid publication of original manuscripts and provocative review articles, it provides essential reading for basic scientists and clinicians researching in this rapidly expanding field. In determining content, the primary considerations are excellence, relevance and novelty. While Journal of Neuroendocrinology reflects the broad scientific and clinical interests of the BSN membership, the editorial team, led by Professor Julian Mercer, ensures that the journal’s ethos, authorship, content and purpose are those expected of a leading international publication.
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