title: Olivocerebellar projections modify hereditary Purkinje cell degeneration.
abstract: Brainstem inferior olivary neurons, through their olivocerebellar efferent projections, dynamically regulate the structure and function of Purkinje neurons. To test the hypothesis that the inferior olive can epigenetically modify adult-onset hereditary Purkinje cell death, olivocerebellar projections were destroyed by 3-acetylpyridine chemoablation of the inferior olive in Shaker mutant rats. Starting around seven weeks of age, mutant Purkinje cells degenerate in a highly predictable spatial and temporal pattern. Chemoablation of the inferior olive at the onset of hereditary Purkinje cell degeneration accelerated the temporal pattern of Purkinje cell death from a natural phenotypic course of six to eight weeks to one and two weeks. When chemoablation of the inferior olive was performed three and a half weeks earlier, the onset of Purkinje cell death was accelerated by seven to 10days, but the spatial pattern and natural rate of temporal degeneration was maintained. Chemoablation of the inferior olive in normal rats did not result in any apparent death of Purkinje cells. These findings indicate that the olivocerebellar system can markedly modify hereditary Purkinje cell death. The accelerated death of Purkinje cells following chemoablation of the inferior olive can result from either the interruption of a trophic signal by climbing fiber deafferentation or parallel fiber excitotoxicity due to cortical disinhibition, but not due to olivocerebellar excitotoxicity.
authors.affiliation: Francis and Doris Murphy Neuroanatomy Research Laboratory, Department of Anatomy and Neurobiology, and Department of Surgery (Neurosurgery), Saint Louis University School of Medicine, St Louis, MO 63104, USA. tolbertd@slu.edu
authors.forename: D L
authors.initials: DL
authors.lastname: Tolbert
authors.forename: B R
authors.initials: BR
authors.lastname: Clark
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D064026:Calbindins; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002525:Cerebellar Cortex / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D003714:Denervation / Q000009:adverse effects; D004195:Disease Models, Animal; D006246:Harmaline / Q000494:pharmacology; D008297:Male; D009410:Nerve Degeneration / Q000139:chemically induced / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D009434:Neural Pathways / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D009498:Neurotoxins / Q000494:pharmacology; D009536:Niacinamide / Q000494:pharmacology; D009847:Olivary Nucleus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D010320:Parvalbumins / Q000378:metabolism; D011689:Purkinje Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D013132:Spinocerebellar Degenerations / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*
chemical_list: D064026:Calbindins; D009498:Neurotoxins; D010320:Parvalbumins; D011725:Pyridines; D064030:S100 Calcium Binding Protein G; C010835:3-acetylpyridine; D009536:Niacinamide; D006246:Harmaline