海马体和下丘脑神经元中腺苷1受体表达与功能的比较分析
Comparative analysis of adenosine 1 receptor expression and function in hippocampal and hypothalamic neurons.
作者信息
Wegmann Lea, Haas Helmut L, Sergeeva Olga A
机构信息
Medical Faculty and University Hospital, Institute of Neural and Sensory Physiology, Heinrich Heine University Düsseldorf, 40225, Düsseldorf, Germany.
Medical Faculty and University Hospital, Institute of Clinical Neurosciences and Medical Psychology, Heinrich Heine University Düsseldorf, 40225, Düsseldorf, Germany.
出版信息
Inflamm Res. 2025 Jan 8;74(1):11. doi: 10.1007/s00011-024-01980-8.
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 GABA 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.
背景
腺苷作为三磷酸腺苷（ATP）的降解产物，是一种睡眠压力因子。腺苷1受体（A1R）反映睡眠需求。结节乳头体核（TMN）的组胺能神经元（HN）仅在清醒时放电并促进觉醒。它们均表达GABA受体并受GABA抑制。腺苷是否有助于使其沉默？
研究对象与处理
在小鼠脑片和原代解离培养物中研究对腺苷的反应。对于HN鉴定，使用了单细胞（sc）逆转录聚合酶链反应（RT-PCR）、报告蛋白和药理学方法。同时对海马齿状回颗粒层细胞（DGgc）进行了研究。
方法
采用膜片钳记录或微电极阵列记录放电频率。通过scRT-PCR和半定量PCR研究A1R的表达。
结果
多数DGgc通过A1R受到抑制，在10个PDZd2阳性DGgc中有7个通过scRT-PCR检测到A1R；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水平比下丘脑尾部（后部）高6倍。与海马培养物相比，下丘脑培养物中对腺苷的反应较弱。
结论
多数HN不受腺苷抑制。
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