PMID- 21946266
OWN - NLM
STAT- MEDLINE
DCOM- 20111220
LR  - 20181201
IS  - 1090-2430 (Electronic)
IS  - 0014-4886 (Linking)
VI  - 232
IP  - 2
DP  - 2011 Dec
TI  - Higher free D-aspartate and N-methyl-D-aspartate levels prevent striatal 
      depotentiation and anticipate L-DOPA-induced dyskinesia.
PG  - 240-50
LID - 10.1016/j.expneurol.2011.09.013 [doi]
AB  - In Parkinson's disease (PD) progressive alteration of striatal 
      N-methyl-D-aspartate receptors (NMDARs) signaling has emerged as a considerable 
      factor for the onset of the adverse motor effects of long-term levodopa (l-DOPA) 
      treatment. In this regard, the NMDAR channel blocker amantadine is so far the 
      only drug available for clinical use that attenuates L-DOPA-induced dyskinesia 
      (LID). In this study, we examined the influence of a basal corticostriatal 
      hyper-glutamatergic transmission in the appearance of dyskinesia, using a genetic 
      mouse model lacking D-Aspartate Oxidase (DDO) enzyme (Ddo(-/-) mice). We found 
      that, in Ddo(-/-) mice, non-physiological, high levels of the endogenous free 
      D-amino acids D-aspartate (D-Asp) and NMDA, known to stimulate NMDAR 
      transmission, resulted in the loss of corticostriatal synaptic depotentiation and 
      precocious expression of LID. Interestingly, the block of depotentiation precedes 
      any change in dopaminergic transmission associated to 6-OHDA lesion and l-DOPA 
      treatment. Indeed, lesioned mutant mice display physiological L-DOPA-dependent 
      enhancement of striatal D1 receptor/PKA/protein phosphatase-1 and ERK signaling. 
      Moreover, in line with synaptic rearrangements of NMDAR subunits occurring in 
      dyskinetic animal models, a short L-DOPA treatment produces a dramatic and 
      selective reduction of the NR2B subunit in the striatal post-synaptic fraction of 
      Ddo(-/-) lesioned mutants but not in controls. These data indicate that a 
      preexisting hyper-glutamatergic tone at NMDARs in Ddo(-/-) mice produce abnormal 
      striatal synaptic changes that, in turn, facilitate the onset of LID.
CI  - Copyright (c) 2011 Elsevier Inc. All rights reserved.
FAU - Errico, Francesco
AU  - Errico F
AD  - Laboratory of Behavioural Neuroscience, Ceinge Biotecnologie Avanzate, Naples, 
      Italy.
FAU - Bonito-Oliva, Alessandra
AU  - Bonito-Oliva A
FAU - Bagetta, Vincenza
AU  - Bagetta V
FAU - Vitucci, Daniela
AU  - Vitucci D
FAU - Romano, Rosaria
AU  - Romano R
FAU - Zianni, Elisa
AU  - Zianni E
FAU - Napolitano, Francesco
AU  - Napolitano F
FAU - Marinucci, Silvia
AU  - Marinucci S
FAU - Di Luca, Monica
AU  - Di Luca M
FAU - Calabresi, Paolo
AU  - Calabresi P
FAU - Fisone, Gilberto
AU  - Fisone G
FAU - Carta, Manolo
AU  - Carta M
FAU - Picconi, Barbara
AU  - Picconi B
FAU - Gardoni, Fabrizio
AU  - Gardoni F
FAU - Usiello, Alessandro
AU  - Usiello A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110917
PL  - United States
TA  - Exp Neurol
JT  - Experimental neurology
JID - 0370712
RN  - 0 (Antiparkinson Agents)
RN  - 0 (Receptors, AMPA)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (Sympatholytics)
RN  - 46627O600J (Levodopa)
RN  - 4SR0Q8YD1X (D-Aspartic Acid)
RN  - 6384-92-5 (N-Methylaspartate)
RN  - 8HW4YBZ748 (Oxidopamine)
RN  - EC 1.4.3.1 (D-Aspartate Oxidase)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - TFZ3H25BS1 (glutamate receptor ionotropic, AMPA 1)
SB  - IM
MH  - Action Potentials/physiology
MH  - Animals
MH  - Antiparkinson Agents/toxicity
MH  - Corpus Striatum/*metabolism/pathology/physiopathology
MH  - D-Aspartate Oxidase/genetics/metabolism
MH  - D-Aspartic Acid/*metabolism
MH  - Dyskinesia, Drug-Induced/*metabolism/pathology
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Levodopa/*toxicity
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - N-Methylaspartate/*metabolism
MH  - Neuronal Plasticity/physiology
MH  - Oxidopamine/toxicity
MH  - Parkinsonian Disorders/*drug therapy/metabolism/pathology
MH  - Phosphorylation/physiology
MH  - Receptors, AMPA/metabolism
MH  - Receptors, N-Methyl-D-Aspartate/metabolism
MH  - Sympatholytics/toxicity
MH  - Synapses/metabolism/pathology
EDAT- 2011/09/29 06:00
MHDA- 2011/12/21 06:00
CRDT- 2011/09/28 06:00
PHST- 2011/06/22 00:00 [received]
PHST- 2011/08/31 00:00 [revised]
PHST- 2011/09/09 00:00 [accepted]
PHST- 2011/09/28 06:00 [entrez]
PHST- 2011/09/29 06:00 [pubmed]
PHST- 2011/12/21 06:00 [medline]
AID - S0014-4886(11)00321-9 [pii]
AID - 10.1016/j.expneurol.2011.09.013 [doi]
PST - ppublish
SO  - Exp Neurol. 2011 Dec;232(2):240-50. doi: 10.1016/j.expneurol.2011.09.013. Epub 
      2011 Sep 17.