title: Decreased hippocampal expression of calbindin D28K and cognitive impairment in MELAS.
abstract: Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is a maternally inherited mitochondrial syndrome characterized by seizures, migrainous headaches, lactic acidosis, vomiting, and recurrent stroke-like episodes. Patients often suffer from cognitive dysfunction of unclear pathogenesis. In this study, we explored a possible link between cognitive dysfunction and hippocampal expression of calbindin D(28KD) (CB), a high affinity calcium-binding protein, in four MELAS patients, using post mortem hippocampal tissues. We found significantly reduced CB levels in all patients by immunohistochemistry, Western blot, and quantitative real-time PCR. Reduction in CB expression has been associated with aging and with neurodegenerative disorders, including Alzheimer's disease. We postulate that the reduced CB expression may play a role in the cognitive abnormalities associated with MELAS.
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Valentina
authors.initials: V
authors.lastname: Emmanuele
authors.forename: Angels
authors.initials: A
authors.lastname: Garcia-Cazorla
authors.forename: Hua-Bin
authors.initials: HB
authors.lastname: Huang
authors.forename: Jorida
authors.initials: J
authors.lastname: Coku
authors.forename: Beatriz
authors.initials: B
authors.lastname: Dorado
authors.forename: Etty P
authors.initials: EP
authors.lastname: Cortes
authors.forename: Kristin
authors.initials: K
authors.lastname: Engelstad
authors.forename: Darryl C
authors.initials: DC
authors.lastname: De Vivo
authors.forename: Salvatore
authors.initials: S
authors.lastname: Dimauro
authors.forename: Eduardo
authors.initials: E
authors.lastname: Bonilla
authors.forename: Kurenai
authors.initials: K
authors.lastname: Tanji
mesh_terms: D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics; D064092:Calbindin 1; D064026:Calbindins; D003072:Cognition Disorders / Q000378:metabolism* / Q000473:pathology* / Q000523:psychology; D005260:Female; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D017241:MELAS Syndrome / Q000378:metabolism* / Q000473:pathology* / Q000523:psychology; D008297:Male; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D064030:S100 Calcium Binding Protein G / Q000096:biosynthesis*
chemical_list: C576498:CALB1 protein, human; D064092:Calbindin 1; D064026:Calbindins; D009419:Nerve Tissue Proteins; D064030:S100 Calcium Binding Protein G