Effects of the cholesterol biosynthesis inhibitor ay9944 on organotypic cultures ofmouse spinal cord. Retarded myelinogenesis and induction of cytoplasmic inclusions.
Young cultures of fetal mouse spinal cord were exposed to nutrient medium containingAY9944 [trans-1,4-bis(2-chlorobenzylaminomethyl)cyclohexane dihydrochloride], apotent cholesterol biosynthesis inhibitor, and their reactions were studied by light and electron microscopy.  AY9944 treatment for 4 to 7 days retarded cultures revealed anaccumulation of numerous intracytoplasmic inclusions in perikarya of neurons, astrocytes,and oligodendrocytes.  These inclusions were also found in dendritic processes, myelinated axons, and presynaptic terminals.  These inclusions were composed of concentric lamellar structures or of reticular internal structures.  Although considerable improvement of myelination and diminution of cytoplasmic inclusions were noted following the removal of the inhibitor and the restitution in normal nutrient medium, a complete recovery oflesions was not observed during the 3-week restitution period in vitro.
D000818:Animals; D001253:Astrocytes / Q000648:ultrastructure; D001369:Axons / Q000648:ultrastructure; D002784:Cholesterol / Q000096:biosynthesis*; D003470:Culture Media; D003510:Cyclohexanes / Q000494:pharmacology*; D003712:Dendrites / Q000648:ultrastructure; D005260:Female; D005333:Fetus; D002479:Inclusion Bodies / Q000187:drug effects* / Q000648:ultrastructure; D051379:Mice; D008854:Microscopy, Electron; D009186:Myelin Sheath / Q000187:drug effects* / Q000196:embryology; D009474:Neurons / Q000648:ultrastructure; D009836:Oligodendroglia / Q000648:ultrastructure; D009924:Organ Culture Techniques; D011247:Pregnancy; D013116:Spinal Cord / Q000187:drug effects* / Q000648:ultrastructure; D013997:Time Factors; D001371:trans-1,4-Bis(2-chlorobenzaminomethyl)cyclohexane Dihydrochloride / Q000494:pharmacology*
D003470:Culture Media; D003510:Cyclohexanes; D001371:trans-1,4-Bis(2-chlorobenzaminomethyl)cyclohexane Dihydrochloride; D002784:Cholesterol