UC San Diego

To date, there are at least two locations in the mammalian brain where new neurons are being born, one of which is the subgranular zone of the hippocampus. These newborn neurons are fully capable of integrating and functioning as part of the hippocampal circuitry, thereby improving performance on learning and memory tasks. Hippocampal neurogenesis may be modulated by different stimuli and treatments, such as brain-derived neurotrophic factor (BDNF). In the present study, BDNF vector is delivered into the entorhinal cortex. BDNF is anterogradely transported from the entorhinal cortex into the aged non- human primate hippocampus. Newborn cells are detected by use of 5-bromo-2'-deoxyuridine (BrdU). Neurogenesis was measured by the number of BrdU+ cells that colabeled with either a mature neuronal marker (NeuN) or an immature neuronal marker (DCX). It was determined that while BDNF gene delivery resulted in an increased trend of surviving cells, there was no difference in the number of these newborn cells that differentiate into neurons. While the rate of neurogenesis was unaffected by aging, there was an observed decline in the total number of BrdU+ cells colabeled with a neuronal marker as well as the total amount of DCX+ cells. There was, however, a large portion of the BrdU+ cells that remained unidentified. No BrdU+ cell was colocalized with glial fibrillary acidic protein (GFAP), present in astrocytes and neural progenitor cells (NPCs). Lastly, there was no effect of treatment on maturation of newborn neurons as measured by migration and branching of DCX+ cells