Comparative analysis of adenosine 1 receptor expression and function in hippocampal and hypothalamic neurons.

IF 4.8 3区 医学 Q2 CELL BIOLOGY Inflammation Research Pub Date : 2025-01-08 DOI:10.1007/s00011-024-01980-8
Lea Wegmann, Helmut L Haas, Olga A Sergeeva
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Abstract

Background: Adenosine, an ATP degradation product, is a sleep pressure factor. The adenosine 1 receptor (A1R) reports sleep need. Histaminergic neurons (HN) of the tuberomamillary nucleus (TMN) fire exclusively during wakefulness and promote arousal. All of them express GABAA receptors and are inhibited by GABA. Does adenosine contribute to their silencing?

Subjects and treatment: Responses to adenosine were studied in mouse brain slices and primary dissociated cultures. For HN identification single-cell (sc)RT-PCR, reporter protein and pharmacology were used. Hippocampal Dentate Gyrus granular layer cells (DGgc) were studied in parallel.

Methods: Firing frequency was recorded in patch-clamp configuration or by microelectrode arrays. A1R-expression was studied by scRT-PCR and semiquantitative PCR.

Results: Most DGgc were inhibited through A1R, detected with scRT-PCR in 7 out of 10 PDZd2-positive DGgc; all HN were A1R negative. One HN out of 25 was inhibited by adenosine. The A1R mRNA level in the hippocampus was 6 times higher than in the caudal (posterior) hypothalamus. Response to adenosine was weaker in hypothalamic compared to hippocampal cultures.

Conclusions: Most HN are not inhibited by adenosine.

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海马与下丘脑神经元腺苷1受体表达与功能的比较分析。
背景:腺苷是一种ATP降解产物,是一种睡眠压力因子。腺苷1受体(A1R)报告睡眠需求。结节乳头核(TMN)的组胺能神经元(HN)只在清醒时放电并促进觉醒。它们均表达GABAA受体,并受GABA抑制。腺苷是否导致了它们的沉默?实验对象和治疗方法:在小鼠脑切片和原代分离培养物中研究对腺苷的反应。利用单细胞RT-PCR技术,结合报告蛋白和药理学方法对HN进行鉴定。平行研究海马齿状回颗粒层细胞(DGgc)。方法:用膜片钳或微电极阵列记录放电频率。采用scRT-PCR和半定量PCR检测a1r的表达。结果:大多数DGgc通过A1R被抑制,10个pdzd2阳性DGgc中有7个通过scRT-PCR检测到;所有HN均为A1R阴性。25个HN中有1个被腺苷抑制。海马中的A1R mRNA水平比下丘脑尾侧(后)高6倍。下丘脑对腺苷的反应弱于海马体培养。结论:大多数HN不受腺苷的抑制。
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来源期刊
Inflammation Research
Inflammation Research 医学-免疫学
CiteScore
9.90
自引率
1.50%
发文量
134
审稿时长
3-8 weeks
期刊介绍: Inflammation Research (IR) publishes peer-reviewed papers on all aspects of inflammation and related fields including histopathology, immunological mechanisms, gene expression, mediators, experimental models, clinical investigations and the effect of drugs. Related fields are broadly defined and include for instance, allergy and asthma, shock, pain, joint damage, skin disease as well as clinical trials of relevant drugs.
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