TY - JOUR
T1 - Effects of Anti-NMDA Antibodies on Functional Recovery and Synaptic Rearrangement Following Hemicerebellectomy
AU - Laricchiuta, Daniela
AU - Cavallucci, Virve
AU - Cutuli, Debora
AU - de Bartolo, Paola
AU - Caporali, Paola
AU - Foti, Francesca
AU - Finke, Carsten
AU - D’Amelio, Marcello
AU - Manto, Mario
AU - Petrosini, Laura
PY - 2016/3/30
Y1 - 2016/3/30
N2 - The compensation that follows cerebellar lesions is based on synaptic modifications in many cortical and subcortical regions, although its cellular mechanisms are still unclear. Changes in glutamatergic receptor expression may represent the synaptic basis of the compensated state. We analyzed in rats the involvement of glutamatergic system of the cerebello-frontal network in the compensation following a right hemicerebellectomy. We evaluated motor performances, spatial competencies and molecular correlates in compensated hemicerebellectomized rats which in the frontal cortex contralateral to the hemicerebellectomy side received injections of anti-NMDA antibodies from patients affected by anti-NMDA encephalitis. In the compensated hemicerebellectomized rats, the frontal injections of anti-NMDA antibodies elicited a marked decompensation state characterized by slight worsening of the motor symptoms as well as severe impairment of spatial mnesic and procedural performances. Conversely, in the sham-operated group the frontal injections of anti-NMDA antibodies elicited slight motor and spatial impairment. The molecular analyses indicated that cerebellar compensatory processes were related to a relevant rearrangement of glutamatergic synapses (NMDA and AMPA receptors and other glutamatergic components) along the entire cortico-cerebellar network. The long-term maintenance of the rearranged glutamatergic activity plays a crucial role in the maintenance of recovered function.
AB - The compensation that follows cerebellar lesions is based on synaptic modifications in many cortical and subcortical regions, although its cellular mechanisms are still unclear. Changes in glutamatergic receptor expression may represent the synaptic basis of the compensated state. We analyzed in rats the involvement of glutamatergic system of the cerebello-frontal network in the compensation following a right hemicerebellectomy. We evaluated motor performances, spatial competencies and molecular correlates in compensated hemicerebellectomized rats which in the frontal cortex contralateral to the hemicerebellectomy side received injections of anti-NMDA antibodies from patients affected by anti-NMDA encephalitis. In the compensated hemicerebellectomized rats, the frontal injections of anti-NMDA antibodies elicited a marked decompensation state characterized by slight worsening of the motor symptoms as well as severe impairment of spatial mnesic and procedural performances. Conversely, in the sham-operated group the frontal injections of anti-NMDA antibodies elicited slight motor and spatial impairment. The molecular analyses indicated that cerebellar compensatory processes were related to a relevant rearrangement of glutamatergic synapses (NMDA and AMPA receptors and other glutamatergic components) along the entire cortico-cerebellar network. The long-term maintenance of the rearranged glutamatergic activity plays a crucial role in the maintenance of recovered function.
KW - Anti-NMDA encephalitis
KW - Cerebellar compensation
KW - Glutamate receptors
KW - Morris water maze
KW - Postural and motor behaviors
KW - Rat
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U2 - 10.1007/s12017-016-8390-1
DO - 10.1007/s12017-016-8390-1
M3 - Article
AN - SCOPUS:84962262503
SP - 1
EP - 13
JO - NeuroMolecular Medicine
JF - NeuroMolecular Medicine
SN - 1535-1084
ER -