title: Expression of glutamate receptor subtypes in the spinal cord of control and mnd mice, a model of motor neuron disorder.
abstract: We studied the expression and distribution of glutamate receptor subtypes in the spinal cord of mnd mice, a model of motor neuron disorders and neuronal ceroid lipofuscinosis, and control mice using immunocytochemistry and in situ hybridization. The constitutive subunit of the NMDA ionotropic glutamate receptor, NMDAR1, was expressed in all neurons of the grey matter and was not modified in the spinal cord of mnd mice in either its normal or phosphorylated form. The immunoreactivity of GluR2, but not its mRNA, was increased mainly in the substantia gelatinosa both in presymptomatic and in 8-month-old symptomatic mice, suggesting compensatory changes aimed at reducing the Ca2+ permeability of the receptor channel. In spinal cord of mnd mice, mRNA, and protein levels of GluR3 were low only at the symptomatic stage, possibly as a consequence of motor neuron dysfunction. This was not due to motoneuron degeneration, because the number of choline acetyltransferase (ChAT) immunopositive lumbar motor neurons and the ChAT activity in the spinal cord and hind leg muscles of symptomatic mnd mice were no different from control mice. GluR4 mRNA was increased throughout the grey matter, presumably in relation to the marked microglia activation reported in the grey matter of the lumbar spinal cord in mnd mice. These changes in ionotropic glutamate receptors may alter glutamatergic neurotransmission and play some role in the pathology of mnd mice.
authors.affiliation: Istituto di Ricerche Farmacologiche Mario Negri, Milano, Italy. tiziana@marionegri.it
authors.forename: Tiziana
authors.initials: T
authors.lastname: Mennini
authors.forename: Paolo
authors.initials: P
authors.lastname: Bigini
authors.forename: Teresa
authors.initials: T
authors.lastname: Ravizza
authors.forename: Annamaria
authors.initials: A
authors.lastname: Vezzani
authors.forename: Novella
authors.initials: N
authors.lastname: Calvaresi
authors.forename: Massimo
authors.initials: M
authors.lastname: Tortarolo
authors.forename: Caterina
authors.initials: C
authors.lastname: Bendotti
mesh_terms: D000818:Animals; D002452:Cell Count; D002795:Choline O-Acetyltransferase / Q000096:biosynthesis; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008818:Mice, Neurologic Mutants; D016472:Motor Neuron Disease / Q000378:metabolism* / Q000473:pathology; D009046:Motor Neurons / Q000378:metabolism / Q000473:pathology; D018482:Muscle, Skeletal / Q000294:innervation / Q000473:pathology; D009472:Neuronal Ceroid-Lipofuscinoses / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D018091:Receptors, AMPA / Q000096:biosynthesis / Q000235:genetics; D017470:Receptors, Glutamate / Q000096:biosynthesis* / Q000235:genetics; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis / Q000235:genetics; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology
chemical_list: D002795:Choline O-Acetyltransferase; D012333:RNA, Messenger; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C104723:glutamate receptor ionotropic, AMPA 3; C104724:glutamate receptor ionotropic, AMPA 4; C104722:glutamate receptor ionotropic, AMPA 2