The NMDA receptor complex is altered in an animal model of human cerebral heterotopia

Fabrizio Gardoni, Silvia Pagliardini, Veronica Setola, Stefania Bassanini, Flaminio Cattabeni, Giorgio Battaglia, Monica Di Luca

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Double intraperitoneal injections of methylazoxymethanol (MAM) in pregnant rats induce developmental brain dysgenesis with nodular heterotopia similar to human periventricular nodular heterotopia (PNH) and composed of hyperexcitable neurons. Here we analyzed the NMDA receptor complex and associated proteins in the heterotopic neurons of 2- to 3-month-old MAM-treated rats by means of a combined immunocytochemical/molecular approach. Our data demonstrated a clear reduction of p286-active form of αCaMKII and a selective impairment of both the targeting and the CaMKII-dependent phosphorylation of NR2A/B subunits in the postsynaptic membranes of the MAM-induced heterotopia. The reduced NR2A/B immunofluorescence of the cellular membrane was not due to reduced expression since it was decreased only in postsynaptic fractions but not in the homogenate. NMDA-NR1 and AMPA-GluR2/3 subunits, as well as PSD-95 and total αCaMKII protein levels, were not affected in MAM-treated rats, thus revealing that the overall composition of the postsynaptic fraction was not altered. These data clearly suggest that the molecular organization of the NMDA/αCaMKII complex is selectively altered in the postsynaptic compartment of heterotopic neurons. This alteration can play a role in determining the hyperexcitability of brain heterotopia in MAM rats as well as in human patients affected by PNH.

Original languageEnglish
Pages (from-to)662-675
Number of pages14
JournalJournal of Neuropathology and Experimental Neurology
Volume62
Issue number6
Publication statusPublished - Jun 1 2003

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Calcium-Calmodulin-Dependent Protein Kinase Type 2
N-Methyl-D-Aspartate Receptors
Animal Models
Periventricular Nodular Heterotopia
N-Methylaspartate
Neurons
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Membranes
Brain
Intraperitoneal Injections
Fluorescent Antibody Technique
Proteins
Phosphorylation
methylazoxymethanol

Keywords

  • αCaMKII
  • Cerebral dysgenesis
  • Epilepsy
  • Glutamate
  • Methylazoxymethanol (MAM)
  • NMDA receptor complex

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neuroscience(all)

Cite this

Gardoni, F., Pagliardini, S., Setola, V., Bassanini, S., Cattabeni, F., Battaglia, G., & Di Luca, M. (2003). The NMDA receptor complex is altered in an animal model of human cerebral heterotopia. Journal of Neuropathology and Experimental Neurology, 62(6), 662-675.

The NMDA receptor complex is altered in an animal model of human cerebral heterotopia. / Gardoni, Fabrizio; Pagliardini, Silvia; Setola, Veronica; Bassanini, Stefania; Cattabeni, Flaminio; Battaglia, Giorgio; Di Luca, Monica.

In: Journal of Neuropathology and Experimental Neurology, Vol. 62, No. 6, 01.06.2003, p. 662-675.

Research output: Contribution to journalArticle

Gardoni, F, Pagliardini, S, Setola, V, Bassanini, S, Cattabeni, F, Battaglia, G & Di Luca, M 2003, 'The NMDA receptor complex is altered in an animal model of human cerebral heterotopia', Journal of Neuropathology and Experimental Neurology, vol. 62, no. 6, pp. 662-675.
Gardoni F, Pagliardini S, Setola V, Bassanini S, Cattabeni F, Battaglia G et al. The NMDA receptor complex is altered in an animal model of human cerebral heterotopia. Journal of Neuropathology and Experimental Neurology. 2003 Jun 1;62(6):662-675.
Gardoni, Fabrizio ; Pagliardini, Silvia ; Setola, Veronica ; Bassanini, Stefania ; Cattabeni, Flaminio ; Battaglia, Giorgio ; Di Luca, Monica. / The NMDA receptor complex is altered in an animal model of human cerebral heterotopia. In: Journal of Neuropathology and Experimental Neurology. 2003 ; Vol. 62, No. 6. pp. 662-675.
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