Stress, reelin, and the entorhinal cortex: Exploring the effect of chronic stress on reelin density in the rat entorhinal cortex and the correlations with cognition, emotion, and inflammation
Date
2024
Authors
Kurz, Katerina E.
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Abstract
Chronic stress is a risk factor for depression, Alzheimer’s disease, and other disorders. Reelin is a protein with roles in cortex development, synaptic plasticity, and immune responses. Reelin is dysregulated in the hippocampus, hypothalamus, and other regions in these disorders and others. The entorhinal cortex (EC) plays an important role in episodic and spatial memory: with ties to the hippocampus, reelin expression, and shows alterations in depression. To examine the effect of chronic stress on the reelin positive (reelin+) cells in the EC and the connections to cognitive, emotional, and immune systems, 36 rats underwent a 14 week cyclic chronic stress model of depression. A subset of rats received an injection of reelin on the last day to test whether reelin treatment reverses depression-like behaviour and restores reelin in the EC. Behavioural tests were conducted, and immunohistochemistry was used to stain reelin+ cells. Reelin treatment reversed depression-like behaviour, but no effect of chronic stress on EC reelin+ cell density was observed, suggesting that chronic stress does not affect the levels of reelin+ cells in the EC as it does in other regions such as the dentate gyrus. Correlations were examined between reelin+ cell density, forced swim test immobility, spatial memory, and spleen white pulp (WP) area. There was no relationship between reelin+ cell density and immobility time, however there was a significant correlation between spatial memory and reelin cell density in males. This correlation was disrupted with chronic stress but successfully recovered with a reelin injection, suggesting a sex-specific relationship between spatial memory and reelin levels in the EC. Males showed significant white pulp atrophy and recovery with reelin, but only females showed a significant correlation with reelin+ cell density. This suggests a role of reelin in modulating inflammatory responses, and highlights another sex-specific difference. The disruption by chronic stress in the correlation between cognitive tests and EC reelin+ cells, and the subsequent recovery by a single reelin iv injection should be further explored when considering the putative fast-acting antidepressant actions of reelin, and that cognitive symptoms in depression patients aren’t properly solved by current antidepressant treatment.