Infusion of brain-derived neurotrophic factor into the lateral ventricle of the adult rat leads to new neurons in the parenchyma of the striatum, septum, thalamus, and hypothalamus

The findings that brain-derived neurotrophic factor (BDNF) promotes in vitr o the survival and/or differentiation of postnatal subventricular zone (SVZ ) progenitor cells and increases in vivo the number of the newly generated neurons in the adult rostral migratory stream and olfactory bulb prompted u s to investigate whether the infusion of BDNF influences the proliferation and/or differentiation of cells in other regions of the adult forebrain. We examined the distribution and phenotype of newly generated cells in the ad ult rat forebrain 16 d after intraventricular administration of BDNF in con junction with the cell proliferation marker bromodeoxyuridine (BrdU) for 12 d. BDNF infusion resulted in numerous BrdU(+) cells, not only in the SVZ l ining the infused lateral ventricle, but moreover, in specific parenchymal structures lining the lateral and third ventricles, including the striatum and septum, as well as the thalamus and hypothalamus, in which neurogenesis had never been demonstrated previously during adulthood. In each region, n ewly generated cells expressed the neuronal marker microtubule-associated p rotein-2, or neuron-specific tubulin, identified by the antibody TuJ1. The percentage of the newly generated cells expressing TuJ1 ranged from 27 to 4 2%, suggesting that the adult forebrain has a more profound capacity to pro duce neurons than recognized previously. The extent of cell proliferation a fter BDNF infusion was correlated with the level of expression of full-leng th TrkB, the high-affinity receptor for BDNF, despite the fact that the Brd U(+) cells were not themselves TrkB(+). Collectively, our results demonstra te that the adult brain parenchyma may recruit and/or generate new neurons, which could replace those lost as a result of injury or disease.