Entorhinal cortex regulation of multiple brain-derived neurotrophic factor promoters in the rat hippocampus

Abstract

Developmental or degenerative damage of the neuronal architecture in the entorhinal cortex may disintegrate a functional part of hippocampal input since the entorhinal cortex provides a major source of neocortical and subcortial input to the hippocampus. These alterations, such as seen in Alzheimer's disease, 15 schizophrenia 5 and temporal lobe epilepsy 29 are likely to be associated with cognitive deficits. To understand the basis for pathological changes in the corticohippocampal loop it is important to study mechanisms involved in neuronal plasticity. Brain-derived neurotrophic factor provides a possible substrate to mediate such plasticity. We have previously provided evidence that stimulation of hippocampal afferents transynaptically increase the level of brain-derived neurotrophic factor messenger RNA within the hippocampus. 21 In the present study we have investigated whether different brain-derived neurotrophic factor messenger RNAs are specifically regulated in the hippocmapus. We provide evidence for a differential and dose-dependent regulation of the different brain-derived neurotrophic factor promoters in the hippocampus by afferents in the entorhinal cortex. Our finding of a graded regulation is in contrast to earlier evidence of an “all-or-none” type of regulation. 3