title: Subsurface cistern (SSC) proliferation in Purkinje cells of the rat cerebellum in response to acute and chronic exposure to paint thinner: A light and electron microscopy study.
abstract: Intentional inhalation and occupational exposure are two ways humans are exposed to thinner, a widely employed solvent in industry. Inhalation of thinner induces toxic effects in various organs, with the cerebellum being one of the most affected structures of the CNS. The aim of this work was to describe specific structural alterations of cerebellum Purkinje cells in rats following exposure to thinner for 16 weeks. A histological analysis of the cerebellum of solvent-exposed rats revealed swollen Purkinje cell dendrites surrounded by empty space, and electronic microscopy showed an increase in the number of subsurface cisterns (SSCs) within their dendritic processes. After a period of non-exposure, the number of SSCs decreased without reaching normal levels, suggesting a degree of plasticity. Purkinje cell SSCs, which are derived from smooth endoplasmic reticulum, contain inositol trisphosphate receptors (IP3Rs), ryanodine receptors (RR), and a recently identified characteristic cluster of large conductance calcium-activated potassium (BKCa) channels. We found that SSCs in Purkinje cell dendrites were closely associated with mitochondria, and immunofluorescence microscopy showed higher levels of RR and calbindin receptors (CB), in Purkinje cells of exposed than normal rats. These changes are probably related to behavioral manifestations of cerebellar alterations, such as imbalance and ataxia, consistent with the suggested involvement of increases in SSCs in ataxia in rats and humans. This increase in SSCs, taken together with the localization of RR, IP3R and BKCa proteins in this structure, suggests altered intracellular calcium-buffering processes in the Purkinje cells of thinner-exposed rats.
authors.affiliation: Departamento de Farmacia, Universidad de Guanajuato, Noria Alta, Guanajuato CP 36050, Mexico. Electronic address: alfarominerva@yahoo.fr.
authors.forename: Minerva
authors.initials: M
authors.lastname: Martínez-Alfaro
authors.affiliation: Instituto de Neurobiología UNAM Campus Juriquilla, Boulevard Juriquilla No. 3002, Querétaro CP 76230, Mexico. Electronic address: carabez1@unam.mx.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Cárabez-Trejo
authors.affiliation: Instituto de Neurobiología UNAM Campus Juriquilla, Boulevard Juriquilla No. 3002, Querétaro CP 76230, Mexico.
authors.forename: Francisca
authors.initials: F
authors.lastname: Sandoval-Zapata
authors.affiliation: Hospital Regional de Alta Especialidad del Bajío, León, Guanajuato CP 37660, Mexico.
authors.forename: Verónica
authors.initials: V
authors.lastname: Morales-Tlalpan
authors.affiliation: Instituto de Neurobiología UNAM Campus Juriquilla, Boulevard Juriquilla No. 3002, Querétaro CP 76230, Mexico.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Palma-Tirado
mesh_terms: D000818:Animals; D064026:Calbindins / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D004305:Dose-Response Relationship, Drug; D019570:Inhalation Exposure; D008297:Male; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D018384:Oxidative Stress / Q000187:drug effects; D010150:Paint; D011689:Purkinje Cells / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D017208:Rats, Wistar; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D012997:Solvents / Q000633:toxicity*; D014835:Volatilization
chemical_list: D064026:Calbindins; D019837:Ryanodine Receptor Calcium Release Channel; D012997:Solvents
keywords: Cerebellum plasticity; Ryanodine and calbindin receptors; Solvent inhalation; Subsurface cisterns membrane