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.