由GPRCs激活的改变的PLCβ/IP3/Ca2+信号通路在来自被诊断为精神分裂症的患者的嗅觉神经前体细胞中
Zuly A Sánchez-Florentino1,2, Bianca S Romero-Martínez3, Edgar Flores-Soto3
1Posgrado en Biología Experimental, Universidad Autónoma Metropolitana-Iztapalapa, Mexico City 09340, CP, Mexico.
Biomedicines
|October 26, 2024
概括
这项研究揭示了从精神分裂症患者的嗅觉神经元前体细胞中的脂酶Cββ (PLCβ) /伊诺西托三酸盐 (IP3) / (Ca2+) 信号通路的功能障碍,表明这种疾病的潜在细胞机制.
科学领域:
- 神经科学是一个神经科学.
- 细胞信号传输 细胞信号传输
- 精神疾病 精神疾病
背景情况:
- 精神分裂症 (SZ) 是一种慢性精神疾病,影响全球1%的人口.
- 在SZ患者中改变的脂酶Cβ (PLCβ) 表达表明了PLCβ/伊诺西托三酸盐 (IP3) / (Ca2+) 信号通路的失调.
- 关于这种途径在SZ患者的神经细胞中的功能存在有限的数据.
研究的目的:
- 研究从SZ患者获得的人类嗅觉神经元前体细胞 (hONPCs) 中的PLCβ/IP3/Ca2+通路的功能.
- 为了比较该途径在SZ衍生的hONPCs与健康受试者 (HS) 的活性.
主要方法:
- 来自SZ患者和HS患者的人类嗅觉神经元前体细胞 (hONPCs) 被培养.
- 使用G蛋白合受体 (GPCR) 配体和PLCβ和IP3受体的直接激活剂激活了PLCβ/IP3/Ca2+通路.
- 用微光度和Ca2+成像测量细胞质Ca2+水平;用ELISA量化IP3度;通过免疫光检测评估PLCβ异型表达.
主要成果:
- 与HS衍生的细胞相比,SZ衍生的hONPCs在GPCR或直接通路激活时显著减少了Ca2+的增加.
- 在SZ衍生细胞中,PLCβ1和PLCβ3异型的相对数量和IP3的产生减少了.
- 这些发现表明,精神分裂症患者的hONPCs中PLCβ/IP3/Ca2+信号级联中的功能缺陷.
结论:
- 这项研究表明,从精神分裂症患者获得的hONPCs中,PLCβ/IP3/Ca2+信号通路的显著受损.
- 这种途径功能障碍可能代表一个关键的细胞异常,有助于精神分裂症的病理生理学.
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