Reduction in hippocampal GABAergic transmission in a low birth weight rat model of depression.

IF 3.8 4区 医学 Q1 Medicine
Acta Neuropsychiatrica Pub Date : 2023-12-01 Epub Date: 2023-03-10 DOI:10.1017/neu.2023.18
Zita Dósa, Jose Luis Nieto-Gonzalez, Betina Elfving, Karin Sørig Hougaard, Mai Marie Holm, Gregers Wegener, Kimmo Jensen
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Abstract

Prenatal stress is believed to increase the risk of developing neuropsychiatric disorders, including major depression. Adverse genetic and environmental impacts during early development, such as glucocorticoid hyper-exposure, can lead to changes in the foetal brain, linked to mental illnesses developed in later life. Dysfunction in the GABAergic inhibitory system is associated with depressive disorders. However, the pathophysiology of GABAergic signalling is poorly understood in mood disorders. Here, we investigated GABAergic neurotransmission in the low birth weight (LBW) rat model of depression. Pregnant rats, exposed to dexamethasone, a synthetic glucocorticoid, during the last week of gestation, yielded LBW offspring showing anxiety- and depressive-like behaviour in adulthood. Patch-clamp recordings from dentate gyrus granule cells in brain slices were used to examine phasic and tonic GABAA receptor-mediated currents. The transcriptional levels of selected genes associated with synaptic vesicle proteins and GABAergic neurotransmission were investigated. The frequency of spontaneous inhibitory postsynaptic currents (sIPSC) was similar in control and LBW rats. Using a paired-pulse protocol to stimulate GABAergic fibres impinging onto granule cells, we found indications of decreased probability of GABA release in LBW rats. However, tonic GABAergic currents and miniature IPSCs, reflecting quantal vesicle release, appeared normal. Additionally, we found elevated expression levels of two presynaptic proteins, Snap-25 and Scamp2, components of the vesicle release machinery. The results suggest that altered GABA release may be an essential feature in the depressive-like phenotype of LBW rats.

低出生体重抑郁症大鼠模型的海马 GABA 能传导减少。
产前压力被认为会增加罹患神经精神疾病(包括重度抑郁症)的风险。早期发育过程中的不良遗传和环境影响,如糖皮质激素暴露过多,可导致胎儿大脑发生变化,并与日后的精神疾病有关。GABA 能抑制系统的功能障碍与抑郁症有关。然而,人们对情绪障碍中 GABA 能信号的病理生理学还知之甚少。在此,我们研究了低出生体重(LBW)抑郁模型大鼠的 GABA 能神经传递。妊娠大鼠在妊娠最后一周暴露于地塞米松(一种合成糖皮质激素),所产的低出生体重后代在成年后表现出焦虑和抑郁样行为。研究人员利用对大脑切片中齿状回颗粒细胞的膜片钳记录来检测相性和强直性 GABAA 受体介导的电流。研究还调查了与突触小泡蛋白和GABA能神经递质相关的部分基因的转录水平。对照组大鼠和 LBW 大鼠的自发抑制性突触后电流(sIPSC)频率相似。使用成对脉冲方案刺激冲击颗粒细胞的 GABA 能纤维,我们发现 LBW 大鼠释放 GABA 的几率有所下降。然而,反映量子囊泡释放的强直性 GABA 能电流和微型 IPSC 似乎正常。此外,我们还发现两种突触前蛋白 Snap-25 和 Scamp2 的表达水平升高,它们是囊泡释放机制的组成部分。这些结果表明,GABA释放的改变可能是LBW大鼠抑郁样表型的一个基本特征。
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来源期刊
Acta Neuropsychiatrica
Acta Neuropsychiatrica 医学-精神病学
CiteScore
8.50
自引率
5.30%
发文量
30
审稿时长
6-12 weeks
期刊介绍: Acta Neuropsychiatrica is an international journal focussing on translational neuropsychiatry. It publishes high-quality original research papers and reviews. The Journal''s scope specifically highlights the pathway from discovery to clinical applications, healthcare and global health that can be viewed broadly as the spectrum of work that marks the pathway from discovery to global health.
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