Differential expression of postsynaptic NMDA and AMPA receptor subunits in the hippocampus and prefrontal cortex of the flinders sensitive line rat model of depression.
Glutamatergic abnormalities have recently been implicated in the pathophysiology of depression, and the ionotropic glutamate receptors in particular have been suggested as possible underlying molecular determinants. The Flinders Sensitive Line (FSL) rats constitute a validated model of depression with dysfunctional regulation of glutamate transmission relatively to their control strain Flinders Resistant Line (FRL). To gain insight into how signaling through glutamate receptors may be altered in the FSL rats, we investigated the expression and phosphorylation of AMPA and NMDA receptor subunits in an enriched postsynaptic fraction of the hippocampus and prefrontal cortex. Compared to the hippocampal postsynaptic fractions of FRL rats, FSL rats exhibited decreased and increased levels of the NMDA receptor subunits GluN2A and GluN2B, respectively, causing a lower ratio of GluN2A/GluN2B. The GluA2/GluA3 AMPA receptor subunit ratio was significantly decreased while the expression of the individual GluA1, GluA2, and GluA3 subunits were unaltered including phosphorylation levels of GluA1 at S831 and S845. There were no changes in the prefrontal cortex. These results support altered expression of postsynaptic glutamate receptors in the hippocampus of FSL rats, which may contribute to the depressive-like phenotype of these rats.
Translational Neuropsychiatry Unit, Department of Clinical Medicine Aarhus University, Risskov, Denmark. ctre@clin.au.dk.|Laboratory of Neuropsychopharmacology and Functional Neurogenomics, Department of Pharmacological and Biomolecular Sciences, University of Milano, Milano, Italy. ctre@clin.au.dk.
Giulia
G
Treccani
Translational Neuropsychiatry Unit, Department of Clinical Medicine Aarhus University, Risskov, Denmark.
Kristian
K
Gaarn du Jardin
Translational Neuropsychiatry Unit, Department of Clinical Medicine Aarhus University, Risskov, Denmark.|School of Pharmacy, Faculty of Health Sciences North-West University, Potchefstroom, South Africa.
Gregers
G
Wegener
Translational Neuropsychiatry Unit, Department of Clinical Medicine Aarhus University, Risskov, Denmark.
Heidi Kaastrup
HK
Müller
D000818:Animals; D003863:Depression / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000378:metabolism*; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D051381:Rats; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*
D021122:Protein Subunits; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate
AMPA receptor; NMDA receptor; TIF fraction; Western blot; flinders sensitive line rats