Cognitive Decline Is Associated with Reduced Reelin Expression in the Entorhinal Cortex of Aged Rats

Brain regions and neural circuits differ in their vulnerability to changes that occur during aging and in age-related neurodegenerative diseases. Among the areas that comprise the medial temporal lobe memory system, the layer II neurons of the entorhinal cortex, which form the perforant path input to the hippocampal formation, exhibit early alterations over the course of aging Reelin, a glycoprotein implicated in synaptic plasticity, is expressed by entorhinal cortical layer II neurons. Here, we report that an age-related reduction in reelin expression in the entorhinal cortex is associated with cognitive decline. Using immunohistochemistry and in situ hybridization, we observed decreases in the number of Reelin-immunoreactive cells and reelin messenger RNA expression in the lateral entorhinal cortex of aged rats that are cognitively impaired relative to young adults and aged rats with preserved cognitive abilities. The lateral entorhinal cortex of aged rats with cognitive impairment also exhibited changes in other molecular markers, including increased accumulation of phosphorylated tau and decreased synaptophysin immunoreactivity. Taken together, these findings suggest that reduced reelin expression, emanating from layer II entorhinal neurons, may contribute to network dysfunction that occurs during memory loss in aging.