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生命早期肠道微生物紊乱对成年大鼠海马突触外 GABA-A 受体 α5 和 δ 亚基表达的影响。

Effects of gut microbiota disturbance induced in early life on the expression of extrasynaptic GABA-A receptor α5 and δ subunits in the hippocampus of adult rats.

机构信息

Department of Pathology, Renmin Hospital of Wuhan University, Hubei Provincial, 430060, China.

Department of Pathology, Renmin Hospital of Wuhan University, Hubei Provincial, 430060, China.

出版信息

Brain Res Bull. 2017 Oct;135:113-119. doi: 10.1016/j.brainresbull.2017.09.014. Epub 2017 Sep 28.


DOI:10.1016/j.brainresbull.2017.09.014
PMID:28964773
Abstract

Previous studies have demonstrated that gut microbiota disturbance significantly increases the risk of emotional disorders via the gut-brain axis, but the mechanism is unclear. Furthermore, gamma-aminobutyric acid (GABA) deficits were reported to be implicated in the development of depression and amnesia, but the alterations in the GABA-A receptor subunits that are involved in the pathogenetic process have not been fully elucidated. This study used juvenile rats that were fed ampicillin-Na to establish degree III dysbiosis of the intestinal flora and examined emotional change via the tail suspension test, forced swim test and Morris water maze. Additionally, our study investigated the expression of GABA-A receptor α5 and δ subunits in the hippocampus in adulthood via q-PCR and immunohistochemistry. We focused on the role of GABA-A receptor α5 and δ subunit changes induced by juvenile gut microbiota disturbance in the pathogenesis of emotional disorders in adulthood. In addition, we investigated the protective effects of probiotics and benzodiazepine (clonazepam). Findings showed that juvenile gut microbiota disturbances induced chronic depression and memory loss and reduced the expression of GABA-A receptor α5 and δ subunits in the hippocampus of the adult rat. Furthermore, moderate probiotic administration led to a significant improvement compared to short-term BZ treatment. However, we are aware that these results have been established with a single animal experiment and will require further confirmation with a larger group of individuals. Future directions for the exploration of the effects of gut microbiota disturbance on GABA-A receptor α5 and δ subunits are discussed.

摘要

先前的研究表明,通过肠道-大脑轴,肠道微生物群紊乱显著增加了情绪障碍的风险,但具体机制尚不清楚。此外,据报道,γ-氨基丁酸(GABA)不足与抑郁症和健忘症的发展有关,但涉及发病过程的 GABA-A 受体亚基的变化尚未完全阐明。本研究使用氨苄青霉素-Na 喂养幼年大鼠,建立了肠道菌群 III 度失调,并通过悬尾试验、强迫游泳试验和 Morris 水迷宫检测情绪变化。此外,我们通过 q-PCR 和免疫组织化学研究了成年期海马 GABA-A 受体α5 和δ亚基的表达。我们专注于幼年肠道微生物群紊乱引起的 GABA-A 受体α5 和δ亚基变化在成年期情绪障碍发病机制中的作用。此外,我们还研究了益生菌和苯二氮䓬类药物(氯硝西泮)的保护作用。结果表明,幼年肠道微生物群紊乱会导致慢性抑郁和记忆丧失,并降低成年大鼠海马 GABA-A 受体α5 和δ亚基的表达。此外,与短期 BZ 治疗相比,适度的益生菌给药可显著改善。然而,我们知道这些结果是通过单次动物实验得出的,需要更多的个体来进一步证实。讨论了探索肠道微生物群紊乱对 GABA-A 受体α5 和δ亚基影响的未来方向。

相似文献

[1]
Effects of gut microbiota disturbance induced in early life on the expression of extrasynaptic GABA-A receptor α5 and δ subunits in the hippocampus of adult rats.

Brain Res Bull. 2017-9-28

[2]
Effects of Traumatic Stress Induced in the Juvenile Period on the Expression of Gamma-Aminobutyric Acid Receptor Type A Subunits in Adult Rat Brain.

Neural Plast. 2017

[3]
Downregulation of the alpha5 subunit of the GABA(A) receptor in the pilocarpine model of temporal lobe epilepsy.

Hippocampus. 2003

[4]
[Long-term effects of neonatal recurrent seizures on gamma-aminobutyric acid A receptor alpha1 and gamma2 subunit expressions in the rat brain].

Beijing Da Xue Xue Bao Yi Xue Ban. 2006-12-18

[5]
Effects of toluene exposure during brain growth spurt on GABA(A) receptor-mediated functions in juvenile rats.

Toxicol Sci. 2007-2

[6]
Behavioural and neurochemical consequences of chronic gut microbiota depletion during adulthood in the rat.

Neuroscience. 2016-12-17

[7]
Altered expression of GABA(A) and GABA(B) receptor subunit mRNAs in the hippocampus after kindling and electrically induced status epilepticus.

Neuroscience. 2005

[8]
Selective inhibition of extra-synaptic α5-GABA receptors by S44819, a new therapeutic agent.

Neuropharmacology. 2017-8-12

[9]
Post-weaning social isolation of rats leads to long-term disruption of the gut microbiota-immune-brain axis.

Brain Behav Immun. 2017-11-6

[10]
Native gamma-aminobutyric acid type A receptors from rat hippocampus, containing both alpha 1 and alpha 5 subunits, exhibit a single benzodiazepine binding site with alpha 5 pharmacological properties.

J Pharmacol Exp Ther. 1999-9

引用本文的文献

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The Role of Mitochondrial Dysfunction-Mediated Changes in Immune Cytokine Expression in the Pathophysiology and Treatment of Major Depressive Disorder.

Mol Neurobiol. 2025-8

[2]
Exploring the microbiota-gut-brain axis: impact on brain structure and function.

Front Neuroanat. 2025-2-12

[3]
A systematic review and meta-analysis of basal microbiota and cognitive function in Alzheimer's disease: A potential target for treatment or a contributor to disease progression?

Alzheimers Dement (Amst). 2024-12-27

[4]
The interplay between microbiota and brain-gut axis in epilepsy treatment.

Front Pharmacol. 2024-1-26

[5]
Relationship Between Severity of Gastrointestinal Symptoms and Anxiety Symptoms in Patients with Chronic Gastrointestinal Disease: The Mediating Role of Illness Perception.

Psychol Res Behav Manag. 2023-12-5

[6]
16S rRNA gene sequencing reveals the effect of fluoxetine on gut microbiota in chronic unpredictable stress-induced depressive-like rats.

Ann Gen Psychiatry. 2023-8-3

[7]
Pathogenesis from the microbial-gut-brain axis in white matter injury in preterm infants: A review.

Front Integr Neurosci. 2023-3-16

[8]
Effects of early postnatal life nutritional interventions on immune-microbiome interactions in the gastrointestinal tract and implications for brain development and function.

Front Microbiol. 2022-11-23

[9]
Post-Weaning Treatment with Probiotic Inhibited Stress-Induced Amnesia in Adulthood Rats: The Mediation of GABAergic System and BDNF/c-Fos Signaling Pathways.

Neurochem Res. 2022-8

[10]
The microbiota-gut-brain axis and epilepsy from a multidisciplinary perspective: Clinical evidence and technological solutions for improvement of in vitro preclinical models.

Bioeng Transl Med. 2022-2-25

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