Altered expression of synapse and glutamate related genes in post-mortem hippocampus of depressed subjects

Major depressive disorder (MDD) has been linked to changes in function and activity of the hippocampus, one of the central limbic regions involved in regulation of emotions and mood. The exact cellular and molecular mechanisms underlying hippocampal plasticity in response to stress are yet to be ful...

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Veröffentlicht in:The international journal of neuropsychopharmacology Jg. 16; H. 1; S. 69 - 82
Hauptverfasser: Duric, Vanja, Banasr, Mounira, Stockmeier, Craig A., Simen, Arthur A., Newton, Samuel S., Overholser, James C., Jurjus, George J., Dieter, Lesa, Duman, Ronald S.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Cambridge, UK Cambridge University Press 01.02.2013
Oxford University Press
Schlagworte:
Adult
Aged
Aged, 80 and over
Animals
Depressive Disorder, Major - genetics
Depressive Disorder, Major - metabolism
Depressive Disorder, Major - pathology
Female
Gene Expression Regulation
Genes
Guanylate Kinases - biosynthesis
Guanylate Kinases - genetics
Hippocampus - metabolism
Hippocampus - pathology
Humans
Male
Microtubule-Associated Proteins - biosynthesis
Microtubule-Associated Proteins - genetics
Middle Aged
Nerve Tissue Proteins - biosynthesis
Nerve Tissue Proteins - genetics
Rats
Rats, Sprague-Dawley
Receptors, AMPA - biosynthesis
Receptors, AMPA - genetics
Receptors, Glutamate - biosynthesis
Receptors, Glutamate - genetics
Synapses - genetics
Synapses - metabolism
Synaptosomal-Associated Protein 25 - biosynthesis
Synaptosomal-Associated Protein 25 - genetics
Tumor Suppressor Proteins - biosynthesis
Tumor Suppressor Proteins - genetics
stress
AMPA
depression
hippocampus
post-mortem
ISSN:1461-1457, 1469-5111, 1469-5111
Online-Zugang:Volltext
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Zusammenfassung:Major depressive disorder (MDD) has been linked to changes in function and activity of the hippocampus, one of the central limbic regions involved in regulation of emotions and mood. The exact cellular and molecular mechanisms underlying hippocampal plasticity in response to stress are yet to be fully characterized. In this study, we examined the genetic profile of micro-dissected subfields of post-mortem hippocampus from subjects diagnosed with MDD and comparison subjects matched for sex, race and age. Gene expression profiles of the dentate gyrus and CA1 were assessed by 48K human HEEBO whole genome microarrays and a subgroup of identified genes was confirmed by real-time polymerase chain reaction (qPCR). Pathway analysis revealed altered expression of several gene families, including cytoskeletal proteins involved in rearrangement of neuronal processes. Based on this and evidence of hippocampal neuronal atrophy in MDD, we focused on the expression of cytoskeletal, synaptic and glutamate receptor genes. Our findings demonstrate significant dysregulation of synaptic function/structure related genes SNAP25, DLG2 (SAP93), and MAP1A, and 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl)propanoic acid receptor subunit genes GLUR1 and GLUR3. Several of these human target genes were similarly dysregulated in a rat model of chronic unpredictable stress and the effects reversed by antidepressant treatment. Together, these studies provide new evidence that disruption of synaptic and glutamatergic signalling pathways contribute to the pathophysiology underlying MDD and provide interesting targets for novel therapeutic interventions.
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ISSN:1461-1457
1469-5111
1469-5111
DOI:10.1017/S1461145712000016