Pregnenolone monosulfate is a key precursor to various steroid hormones, including steroid hormones, and possesses multiple biological functions[1-2]. Pregnenolone monosulfate can be utilized in neuroscience research and related nervous system disorders[3-4].
In vitro, Pregnenolone monosulfate (5-300μM) was applied to GH3 pituitary cells for 1 minute, Pregnenolone monosulfate induced a rapid and transient increase in intracellular calcium ion ([Ca²⁺]i) levels. Pregnenolone monosulfate activated L-type voltage-gated calcium channels, mediating extracellular calcium influx[5]. In neonatal rat cerebellar Purkinje cells (P4–10), Pregnenolone monosulfate (25μM) enhanced glutamate release by promoting presynaptic calcium influx through transient receptor potential (TRP) channels, Pregnenolone monosulfate significantly increased AMPA receptor-mediated miniature excitatory postsynaptic currents (AMPA-mEPSCs)[6].
In vivo, in dopamine transporter knockout (DAT-KO) mice (8-10 weeks old), Pregnenolone monosulfate (40 or 80mg/kg; administered either as a single injection or daily for 10 consecutive days via intraperitoneal injection). Pregnenolone monosulfate significantly suppressed hyperlocomotion and stereotypic behaviors, rescued prepulse inhibition deficits, and improved cognitive impairments in novel object recognition and social food preference tests. The therapeutic effects of Pregnenolone monosulfate were mediated through the AKT/GSK3β pathway and increased expression of the hippocampal NMDA receptor NR1 subunit[7]. In wild-type mice (9-10 weeks old), a single subcutaneous injection of Pregnenolone monosulfate (6mg/kg), Pregnenolone monosulfate antagonized Δ9-tetrahydrocannabinol (THC)-induced psychotic-like behaviors, significantly blocked THC-induced cognitive impairments, sensory gating deficits, and reduced social interaction[8].
References:
[1] Vallée M, Vitiello S, Bellocchio L, et al. Pregnenolone can protect the brain from cannabis intoxication. Science. 2014 Jan 3;343(6166):94-8.
[2] Ducharme N, Banks WA, Morley JE, et al. Brain distribution and behavioral effects of progesterone and pregnenolone after intranasal or intravenous administration. Eur J Pharmacol. 2010 Sep 1;641(2-3):128-34.
[3] Shiels A. TRPM3_miR-204: a complex locus for eye development and disease. Hum Genomics. 2020 Feb 18;14(1):7.
[4] Weaver CE Jr, Wu FS, Gibbs TT, et al. Pregnenolone sulfate exacerbates NMDA-induced death of hippocampal neurons. Brain Res. 1998 Aug 24;803(1-2):129-36.
[5] Büküşoğlu C, Sarlak F. Pregnenolone sulfate increases intracellular Ca2+ levels in a pituitary cell line. Eur J Pharmacol. 1996 Feb 29;298(1):79-85.
[6] Zamudio-Bulcock PA, Valenzuela CF. Pregnenolone sulfate increases glutamate release at neonatal climbing fiber-to-Purkinje cell synapses. Neuroscience. 2011 Feb 23;175:24-36.
[7] Wong P, Sze Y, Chang CC, et al. Pregnenolone sulfate normalizes schizophrenia-like behaviors in dopamine transporter knockout mice through the AKT/GSK3β pathway. Transl Psychiatry. 2015 Mar 17;5(3):e528.
[8] Busquets-Garcia A, Soria-Gómez E, Redon B, et al. Pregnenolone blocks cannabinoid-induced acute psychotic-like states in mice. Mol Psychiatry. 2017 Nov;22(11):1594-1603.
Pregnenolone monosulfate是包括甾体酮在内的各种甾体激素的主要前体，具有多种生物学功能[1-2]。Pregnenolone monosulfate可用于神经科学及相关神经系统疾病的研究[3-4]。
在体外，Pregnenolone monosulfate（5-300μM）处理GH3垂体细胞1分钟，可诱导快速、瞬态的细胞内钙离子（[Ca²⁺]i）水平升高，Pregnenolone monosulfate激活L型电压门控钙通道，介导细胞外钙离子内流 [5]。Pregnenolone monosulfate（25μM）处理新生大鼠小脑浦肯野细胞（P4–10），Pregnenolone monosulfate通过瞬时受体电位（TRP）通道介导的突触前钙内流增强谷氨酸释放，显著增加AMPA受体介导的微小兴奋性突触后电流（AMPA-mEPSC）[6]。
在体内，Pregnenolone monosulfate（40或80mg/kg；单次或连续10天腹腔注射）处理多巴胺转运体敲除（DAT-KO）小鼠（8-10周龄），Pregnenolone monosulfate显著抑制小鼠的高活动性和刻板行为，挽救前脉冲抑制缺陷，并改善新物体识别和社会性食物偏好测试中的认知缺陷，Pregnenolone monosulfate通过AKT/GSK3β通路和增加海马NMDA受体NR1亚基表达水平发挥治疗作用[7]。Pregnenolone monosulfate（6mg/kg；单次皮下注射）处理野生型小鼠（9-10周龄），Pregnenolone monosulfate可拮抗Δ9-四氢大麻酚（THC）诱导的精神病样行为，Pregnenolone monosulfate显著阻断THC引起的认知功能损伤、感觉门控缺陷和社会互动减少[8]。