UC San Diego

Entorhinal cortex (EC), primary source of input into the hippocampus, is important for memory and learning. Alzheimer’s patients experience memory loss at early stages of the disease. The memory loss is associated with neuronal atrophy and death, which starts in EC. Previous evidence indicates that brain-derived neurotrophic factor (BDNF) could prevent cell loss and atrophy. The goal of this study was to test lower dosages of adeno-associated virus (AAV) 2-BDNF (1e11vp/ml, 3e11vp/ml and 3e11vp/ml x2 volume) and AAV9-BDNF (3e11vp/ml). Our hypothesis was the BDNF gene delivery into the EC will produce a neuroprotective effect preventing cell lose and cell body atrophy. A perforant pathway lesion was performed in rats that severed the projections from EC layer II neurons to dentate gyrus to induce cell death or atrophy in these neurons. Three days prior to the lesion, subject received treatments into the EC. Rats were euthanized two weeks after lesion, and the brains were analyzed using stereology to quantify the number of neurons and cell atrophy by measuring cell body size. Results showed that BDNF treatment produced a neuroprotective effect that ameliorated cell loss (p<0.01 – 0.05), while control groups had ~30% cell loss. Cell atrophy was decreased within the AAV9 treatment group (p<0.05). Quantification of pAKT cell numbers in ECLII showed no effect of BDNF treatment on pAKT activation after 2 weeks. BDNF does have the potential to prevent early cell lose and atrophy in AD. This might prove to prevent the early memory observed AD.