Desmosterol in developing rat brain

Abstract

The brain of the young rat contains appreciable amounts of desmosterol (24‐dehydrocholesterol). The peak desmosterol concentration is seen during the first week of life and only traces of this sterol are found at 21 days. The spinal cord also contains some desmosterol. Rat brain desmosterol is distributed in the white matter, gray matter and cerebellum and occurs in the same proportion to cholesterol in each of these brain fractions. Rat brain contains a small amount of sterol ester but no appreciable amounts of desmosterol are present in this fraction.Studies carried out in intact animals injected either intraperitoneally or intracerebrally with mevalonic acid‐2‐14C or glucose‐U‐14C indicate the biosynthetic origin or brain desmosterol. Rat brain slices (1舑20 day old) incubated in suitably fortified medium convert sodium acetate‐2‐14C and glucose‐U‐14C to desmosterol, whereas brain slices from adult rats yielded no radioactive desmosterol under similar conditions. When labeled desmosterol was incubated with young rat brain slices, it was converted to cholesterol.When pregnant rats were treated with triparanol (20 mg/kg/day) during the course of their pregnancy, they either resorbed the fetuses or gave birth to small, stillborn litters. The brains of the progeny of triparanol treated mothers contained large amounts of desmosterol as well as another sterol which may be ख7,24‐cholestadiene‐3ॆ‐ol.

Profile of cholesterol-related sterols in aged amyloid precursor protein transgenic mouse brain

“…While high desmosterol levels could be detected in the brain of young rat and mouse (30,31) and in fetal human brain (32), no desmosterol was found in the brain of adult rats (33) or humans (32). The same holds true for the brain of newborn guinea pigs, which is fully myelinated at birth (33). The brain of Sprague-Dawley rats exhibited 4-fold decreasing desmosterol contents between 4 and 21 days, and almost undetectable levels at 6 months of age.…”

Precursors for Cholesterol Synthesis (7‐Dehydrocholesterol, 7‐Dehydrodesmosterol, and Desmosterol): Cholesterol/7‐Dehydrocholesterol Ratio as an Index of Development and Aging in PNS but Not in CNS

“…In contrast,desmosterol (24dehydrocholesterol) was found in the brain of the young rat and mouse (Kritchevsky and Holmes, 1962;Paoletti et a]., 1965) and in fetal human brain (Fumagalli and Paoletti, 1963). It has been associated with the myelination process, because no desmosterol has been detected in the brains of adult rats (Kntchevsky et al, 1965) or humans (Fumagalli and Paoletti, 1963), nor is any present in the brain of the newborn guinea pig, which is fully myelinated at birth (Kritchevsky et al, 1965). Recent reexamination of sterol content in the nervous system has shown that the following free sterols are found in both the optic nerve and cerebral white matter: cholesterol, desmosterol, lanosterol, two dimethylsterols (4,4-dimethyl-5-a-cholesterol-8,24dienes-3-P-01 and 4-a, 14a-dimethyl-5-a-cholesterol-7ene-3-@-01), and probably cholestene.…”

Progestins block cholesterol synthesis to produce meiosis‐activating sterols

“…Under normal metabolic conditions, the rapid conversion of sterol intermediates to cholesterol results in low concentrations of precursors in liver, blood, and most other tissues. Exceptions include the occurrence of elevated concentrations of T-MAS in testicular tissue (1,11), of FF-MAS and T-MAS in preovulatory follicular fluid (11), and of desmosterol in spermatozoa, testis (13,14), human milk (15), and the developing brain (16). The significant levels of MAS in gonadal tissue could result from hormonal regulation, and progestins have long been associated with meiotic events (17,18) and with inhibition of cholesterol synthesis in somatic cells (19,20).…”