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

TLDR

BDNF is known to promote survival and differentiation of subventricular zone progenitors and increase neurons in the rostral migratory stream and olfactory bulb. This study examined whether intraventricular BDNF infusion stimulates proliferation or differentiation of cells in other adult forebrain regions. Adult rats received 12‑day intraventricular BDNF with BrdU labeling, and BrdU+ cells were mapped in the SVZ and parenchymal structures adjacent to the lateral and third ventricles. BDNF infusion induced BrdU+ cells in SVZ and previously neurogenesis‑negative parenchymal regions (striatum, septum, thalamus, hypothalamus), with 27–42 % expressing neuronal markers, proliferation correlating with TrkB expression, indicating the adult forebrain can generate new neurons that may replace lost ones.

Abstract

The findings that brain-derived neurotrophic factor (BDNF) promotes <i>in vitro</i> the survival and/or differentiation of postnatal subventricular zone (SVZ) progenitor cells and increases<i>in vivo</i> the number of the newly generated neurons in the adult rostral migratory stream and olfactory bulb prompted us 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 adult rat forebrain 16 d after intraventricular administration of BDNF in conjunction with the cell proliferation marker bromodeoxyuridine (BrdU) for 12 d. BDNF infusion resulted in numerous BrdU⁺ cells, not only in the SVZ lining 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, newly generated cells expressed the neuronal marker microtubule-associated protein-2, or neuron-specific tubulin, identified by the antibody TuJ1. The percentage of the newly generated cells expressing TuJ1 ranged from 27 to 42%, suggesting that the adult forebrain has a more profound capacity to produce neurons than recognized previously. The extent of cell proliferation after BDNF infusion was correlated with the level of expression of full-length TrkB, the high-affinity receptor for BDNF, despite the fact that the BrdU⁺ cells were not themselves TrkB⁺. Collectively, our results demonstrate that the adult brain parenchyma may recruit and/or generate new neurons, which could replace those lost as a result of injury or disease.