Lack of Glutamate Receptor Subunit Expression Changes in Hippocampal Dentate Gyrus after Experimental Traumatic Brain Injury in a Rodent Model of Depression

Traumatic brain injury (TBI) affects over 69 million people annually worldwide, and those with pre-existing depression have worse recovery. The molecular mechanisms that may contribute to poor recovery after TBI with co-morbid depression have not been established. TBI and depression have many commonalities including volume changes, myelin disruption, changes in proliferation, and changes in glutamatergic signaling. We used a well-established animal model of depression, the Wistar Kyoto (WKY) rat, to elucidate changes after TBI that may influence the recovery trajectory. We compared the histological and molecular outcomes in the hippocampal dentate gyrus after experimental TBI using the lateral fluid percussion injury (LFPI) in the WKY and the parent Wistar (WIS) strain. We showed that WKY had exaggerated myelin loss after LFPI and baseline deficits in proliferation. In addition, we showed that while after LFPI WIS rats exhibited glutamate receptor subunit changes, namely increased GluN2B, the WKY rats failed to show such injury-related changes. These differential responses to LFPI helped to elucidate the molecular characteristics that influence poor recovery after TBI in those with pre-existing depression and may lead to targets for future therapeutic interventions.

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Regulation of glutamate receptor subunit availability by microRNAs

The Journal of Cell Biology ◽

10.1083/jcb.200902062 ◽

2009 ◽

Vol 185 (4) ◽

pp. 685-697 ◽

Cited By ~ 41

Author(s):

Julie Karr ◽

Vasia Vagin ◽

Kaiyun Chen ◽

Subhashree Ganesan ◽

Oxana Olenkina ◽

...

Keyword(s):

Synaptic Transmission ◽

Glutamate Receptors ◽

Glutamate Receptor ◽

Binding Sites ◽

Messenger Rna ◽

Molecular Mechanisms ◽

Neuromuscular Junctions ◽

Synaptic Strength ◽

Receptor Subunit ◽

Glutamate Receptor Subunit

The efficacy of synaptic transmission depends, to a large extent, on postsynaptic receptor abundance. The molecular mechanisms controlling receptor abundance are poorly understood. We tested whether abundance of postsynaptic glutamate receptors (GluRs) in Drosophila neuromuscular junctions is controlled by microRNAs, and provide evidence that it is. We show here that postsynaptic knockdown of dicer-1, the endoribonuclease necessary for microRNA synthesis, leads to large increases in postsynaptic GluR subunit messenger RNA and protein. Specifically, we measured increases in GluRIIA and GluRIIB but not GluRIIC. Further, knockout of MiR-284, a microRNA predicted to bind to GluRIIA and GluRIIB but not GluRIIC, increases expression of GluRIIA and GluRIIB but not GluRIIC proportional to the number of predicted binding sites in each transcript. Most of the de-repressed GluR protein, however, does not appear to be incorporated into functional receptors, and only minor changes in synaptic strength are observed, which suggests that microRNAs primarily regulate Drosophila receptor subunit composition rather than overall receptor abundance or synaptic strength.

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