desmosterol and Seizures

desmosterol has been researched along with Seizures* in 3 studies

Other Studies

3 other study(ies) available for desmosterol and Seizures

ArticleYear
Studies on the mechanisms of the epileptiform activity induced by U186661. I Gross alteration of the lipids of synaptosomes and myelin.
    Epilepsia, 1982, Volume: 23, Issue:3

    U18666A, an inhibitor of desmosterol reductase (a terminal enzyme in cholesterol synthesis), has been found to produce chronic epileptiform activity in laboratory animals. Since desmosterol might substitute for cholesterol in neuronal membranes without detriment, the present study was undertaken to examine the possibility that this drug-induced epilepsy was related to changes in other brain lipids. Chronic treatment of rat with U18666A, beginning at one day of age, resulted in pronounced decreases in the concentration of phospholipids and increases in gangliosides of brain microsomal, synaptosomal, and crude myelin fractions. Since total sterol levels were not changed, the ratio of sterols to phospholipids also increased. If drug treatment was stopped at 4 weeks of age, brain lipids of all subcellular fractions examined returned to normal levels by 8 weeks, and no epileptiform activity was detected. However, following 8 weeks of continuous treatment, epileptiform activity was present, and the changes in brain lipids were focused in the myelin fraction. Phospholipid levels and the sterol:phospholipid ratio of microsomes and synaptosomes, in contrast to myelin, were near normal; however, gangliosides were still clearly elevated in all fractions. A reported ability to induce epileptiform activity in rats by treatment with antiserum to brain gangliosides could indicate a special significance of the altered myelin and synaptic gangliosides to the U18666A-induced epilepsy. We suggest that some epileptiform conditions could be directly related to alterations in the lipid composition of critical neuronal structures.

    Topics: Androstenes; Animals; Brain; Cholesterol; Desmosterol; Female; Gangliosides; Lipid Metabolism; Myelin Sheath; Pregnancy; Rats; Rats, Inbred Strains; Seizures; Synaptosomes

1982
Induction of chronic epileptiform activity in the rat by an inhibitor of cholesterol synthesis, U18666A.
    Brain research, 1978, Jul-14, Volume: 150, Issue:2

    Earlier work in our and other laboratories suggest that alteration of brain lipids, primarily sterols, could be a precondition for the development of epileptiform activity. The present study further tests this hypothesis by attempting to produce chronic epileptiform activity in the rat by a drug which impairs biosynthesis of cerebral cholesterol. Starting one day after birth, weekly injection of the rat with U18666A, 3-beta(2-diethylaminoethoxy)androst-5-en-17-one hydrochloride (10 mg/kg, s.c.), produced a reduced seizure threshold to flurothyl ether and a recurrent, spontaneous seizure state by the sixth and tenth weeks of life, respectively. These conditions were not seen if treatment was delayed until rats were about 4 weeks old. The seizure pattern, as seen by continuous ECoG and EMG recordings, consisted of a 3--5 sec burst of high voltage spiking and corresponding increases in muscle activity. However, major motor seizures were not produced. The total episode lasted 10--15 sec. Seizure frequency ranged from 5 to 21 per day. U18666A decreases cholesterolsynthesis, presumably by inhibiting enzymatic reduction of desmosterol to cholesterol. After the first two weeks of treatment, cerebral cortical cholesterol levels decreased to about 50% of control cortical levels. However, the concentration of cerebral total sterols did not change because desmosterol levels reciprocally increased. In spite of continued drug dosage, cholesterol and desmosterol levels of treated rats approached those of controls by 8 weeks of age. These observations, plus finding that a seizure-prone state did not develop in rats when the onset of drug treatment was postponed until about 4 weeks of age, suggest that alterations of brain sterols early in development of the mammalian brain can result in development of a chronic, epileptiform condition later in life.

    Topics: Age Factors; Androstenes; Animals; Animals, Newborn; Anticholesteremic Agents; Cerebral Cortex; Cholesterol; Chronic Disease; Desmosterol; Disease Susceptibility; Flurothyl; Phospholipids; Rats; Seizures

1978
Induction of a chronic somatosensory epilepsy in the opossum (Didelphis virginiana Kerr) with an inhibitor of cholesterol biosynthesis.
    Brain research, 1973, Dec-21, Volume: 64

    Topics: Androstenes; Animals; Anticholesteremic Agents; Brain; Cholesterol; Desmosterol; Diethylamines; Disease Models, Animal; Electroencephalography; Ketosteroids; Myotonia; Opossums; Seizures; Somatosensory Cortex

1973