title: Loss of DARPP-32 and calbindin in multiple system atrophy.
abstract: We evaluated the immunohistochemical intensities of α-synuclein, phosphorylated α-synuclein (p-syn), dopamine- and cAMP-regulated phosphoprotein of 32 kDa (DARPP-32), calbindin-D 28k, calpain-cleaved carboxy-terminal 150-kDa spectrin fragment, and tyrosine hydroxylase in multiple system atrophy (MSA). The caudate head, anterior putamen, posterior putamen, substantia nigra, pontine nucleus, and cerebellar cortex from six MSA brains, six age-matched disease control brains (amyotrophic lateral sclerosis), and five control brains were processed for immunostaining by standard methods. Immunostaining for α-synuclein, p-syn, or both was increased in all areas examined in oligodendrocytes in MSA. Immunostaining for DARPP-32 and calbindin-D 28k was most prominently decreased in the posterior putamen, where neuronal loss was most prominent. Immunostaining for DARPP-32 and calbindin-D 28k was also diminished in the anterior putamen and caudate head, where neuronal loss was less prominent or absent. Calbindin immunostaining was also decreased in the dorsal tier of the substantia nigra and cerebellar cortex. Loss of immunostaining for DARPP-32 and calbindin-D 28k compared with that of neurons indicates calcium toxicity and disturbance of the phosphorylated state of proteins as relatively early events in the pathogenesis of MSA.
authors.affiliation: Department of Neuroregenerative Medicine, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan, hayahide@med.kitasato-u.ac.jp.
authors.forename: Hideki
authors.initials: H
authors.lastname: Hayakawa
authors.forename: Makiko
authors.initials: M
authors.lastname: Nagai
authors.forename: Aya
authors.initials: A
authors.lastname: Kawanami
authors.forename: Yasuto
authors.initials: Y
authors.lastname: Nakata
authors.forename: Tomoko
authors.initials: T
authors.lastname: Nihira
authors.forename: Mieko
authors.initials: M
authors.lastname: Ogino
authors.forename: Masahiko
authors.initials: M
authors.lastname: Takada
authors.forename: Takaomi
authors.initials: T
authors.lastname: Saido
authors.forename: Jiro
authors.initials: J
authors.lastname: Takano
authors.forename: Makoto
authors.initials: M
authors.lastname: Saegusa
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Mikami
authors.forename: Junichi
authors.initials: J
authors.lastname: Hamada
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Nishiyama
authors.forename: Hideki
authors.initials: H
authors.lastname: Mochizuki
authors.forename: Yoshikuni
authors.initials: Y
authors.lastname: Mizuno
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000378:metabolism*; D064092:Calbindin 1 / Q000378:metabolism*; D016022:Case-Control Studies; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000473:pathology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism
chemical_list: D064092:Calbindin 1; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; C497928:PPP1R1B protein, human; D051844:alpha-Synuclein; D014446:Tyrosine 3-Monooxygenase