The effects of restraint stress on reelin mrna expression in glucocorticoid receptor-overexpressing female mice
Krolweski DM, Hebda-Bauer EK, Wei Q, Shaikh M, Illagan RA, Waselus M, Akil H, Watson SJ
Society for Neuroscience. 2017.
Reelin is a large neuronally secreted excitatory glycoprotein (~450 kDa) whose regulation has been largely studied within cortical and hippocampal interneurons. Alterations in Reelin gene expression amongst these neuronal populations has been linked to psychiatric illness in humans and various stress paradigms utilizing animal models. In order to further examine the effects of stress on Reelin gene activity, we took advantage of a transgenic mouse line that overexpresses glucocorticoid receptors (GRov) in the forebrain and demonstrates increased emotional lability similar to that reported in some psychiatric disorders (Wei et al., 2004).
Methods: GRov (n=16) and wild-type (WT; n=16) female mice were separated into two groups that underwent either 20 minutes of restraint (RST, n=8) or were maintained in their home- cage (controls; CTRL, n=8). Following a post-restraint recovery period of 2 hours and 40 min that took place post-restraint recovery period in the home-cages, animals were sacrificed, brains removed and stored at -80°C. In situ-hybridization using an S35-labeled Reelin cRNA riboprobe was performed on 10 µM-thick sections, exposed on autoradiographic film, and signal quantified using Image J software. Neuroanatomical regions of interest included the motor, prelimbic, infralimbic, piriform, auditory, and entorhinal cortices as well as the hippocampus, striatum, and nucleus accumbens.
Results: Quantitative analyses are currently ongoing and thus far, no significant effect of mouse strain or restraint on Reelin mRNA in the motor, prelimbic or infralimbic prefrontal cortices has been observed. However, within the striatum, Reelin expression was elevated in the GRov phenotype compared to WT mice. Moreover, restraint was associated with a significant reduction in Reelin expression specifically in GRov mice, but not WT mice.
Conclusion: These preliminary findings suggest that stress-mediated activation of glucocorticoid receptors may be connected to dysregulation of Reelin gene expression in subcortical motor circuits. Moreover, the effects of stress on Reelin mRNA may be more pronounced in the striatum vs. prefrontal cortex of female mice.