PMID- 21782871
OWN - NLM
STAT- MEDLINE
DCOM- 20130129
LR  - 20141120
IS  - 1872-9754 (Electronic)
IS  - 0197-0186 (Linking)
VI  - 59
IP  - 6
DP  - 2011 Nov
TI  - Sera from amyotrophic lateral sclerosis patients induce the non-canonical 
      activation of NMDA receptors "in vitro".
PG  - 954-64
LID - 10.1016/j.neuint.2011.07.006 [doi]
AB  - Amyotrophic lateral sclerosis (ALS) is a neuromuscular disease characterized by 
      the selective loss of both upper and lower motoneurons (MNs). The familial form 
      of the illness is associated with mutations in the gene encoding Cu/Zn superoxide 
      dismutase 1 (SOD-1) enzyme, but it accounts for fewer than 10% of cases; the 
      rest, more than 90%, correspond to the sporadic form of ALS. Although many 
      proposals have been suggested over the years, the mechanisms underlying the 
      characteristic selective killing of MN in ALS remain unknown. In this study we 
      tested the effect of sera from sporadic ALS patients on NMDA receptors (NMDAR). 
      We hypothesize that an endogenous seric factor is implicated in neuronal death in 
      ALS, mediated by the modulation of NMDAR. Sera from ALS patients and from healthy 
      subjects were pretreated to inactivate complement pathways and dialyzed to remove 
      glutamate and glycine. IgGs from ALS patients and healthy subjects were obtained 
      by affinity chromatography and dialyzed against phosphate-buffered saline. Human 
      NMDAR were expressed in Xenopus laevis oocytes, and ionic currents were recorded 
      using the two-electrode voltage clamp technique. Sera from sporadic ALS patients 
      induced transient oscillatory currents in oocytes expressing NMDAR with a 
      significantly higher total electrical charge than that induced by sera from 
      healthy subjects. Sera from patients with other neuromuscular diseases did not 
      exert this effect. The currents were inhibited by MK-801, a noncompetitive 
      blocker of NMDAR. The PLC inhibitor, U-73122, and the IP(3) receptor antagonist, 
      2-APB, also inhibited the sera-induced currents. The oscillatory signal recorded 
      was due to internal calcium mobilization. Isolated IgGs from ALS patients 
      significantly affected the activity of oocytes injected with NMDAR, causing a 
      2-fold increase over the response recorded for IgGs from healthy subjects. Our 
      data support the notion that ALS sera contain soluble factors that mobilize 
      intracellular calcium, not opening directly the ionic conductance, but through 
      the non-canonical activation of NMDAR.
CI  - Copyright A(c) 2011 Elsevier B.V. All rights reserved.
FAU - Texido, Laura
AU  - Texido L
AD  - Laboratory of Cellular and Molecular Neurobiology, Department of Pathology and 
      Experimental Therapeutics, Medical School-Bellvitge Campus, University of 
      Barcelona, C/Feixa Llarga s/n, L'Hospitalet de Llobregat, E-08907 Barcelona, 
      Spain.
FAU - Hernandez, Sara
AU  - Hernandez S
FAU - Martin-Satue, Mireia
AU  - Martin-Satue M
FAU - Povedano, Monica
AU  - Povedano M
FAU - Casanovas, Anna
AU  - Casanovas A
FAU - Esquerda, Josep
AU  - Esquerda J
FAU - Marsal, Jordi
AU  - Marsal J
FAU - Solsona, Carles
AU  - Solsona C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110718
PL  - England
TA  - Neurochem Int
JT  - Neurochemistry international
JID - 8006959
RN  - 0 (Blood Proteins)
RN  - 0 (Excitatory Amino Acid Agonists)
RN  - 0 (Neurotoxins)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 3KX376GY7L (Glutamic Acid)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Amyotrophic Lateral Sclerosis/*blood/*physiopathology
MH  - Animals
MH  - Blood Proteins/*toxicity
MH  - Calcium Signaling/*drug effects/physiology
MH  - Excitatory Amino Acid Agonists/toxicity
MH  - Excitatory Postsynaptic Potentials/drug effects/physiology
MH  - Female
MH  - Glutamic Acid/physiology/toxicity
MH  - Humans
MH  - In Vitro Techniques
MH  - Male
MH  - Middle Aged
MH  - Nerve Degeneration/chemically induced/physiopathology
MH  - Neurotoxins/toxicity
MH  - Oocytes
MH  - Receptors, N-Methyl-D-Aspartate/*agonists/physiology
MH  - Synaptic Transmission/drug effects/physiology
MH  - Xenopus laevis
EDAT- 2011/07/26 06:00
MHDA- 2013/01/30 06:00
CRDT- 2011/07/26 06:00
PHST- 2011/02/11 00:00 [received]
PHST- 2011/07/05 00:00 [revised]
PHST- 2011/07/07 00:00 [accepted]
PHST- 2011/07/26 06:00 [entrez]
PHST- 2011/07/26 06:00 [pubmed]
PHST- 2013/01/30 06:00 [medline]
AID - S0197-0186(11)00249-X [pii]
AID - 10.1016/j.neuint.2011.07.006 [doi]
PST - ppublish
SO  - Neurochem Int. 2011 Nov;59(6):954-64. doi: 10.1016/j.neuint.2011.07.006. Epub 
      2011 Jul 18.