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Author Notes:

Dr. Marla B. Luskin, Department of Cell Biology, Emory University School of Medicine, 1648 Pierce Drive, Atlanta, GA 30322. E-mail: luskin@cellbio.emory.edu

We are grateful to Dr. Giri Venkatraman, Dr. Volkan Coskun, and Joanna Bonsall for their critical and helpful comments on this manuscript; and to Dr. Stuart C. Feinstein for his generous gift of anti-TrkB.

Subjects:

Research Funding:

This work was supported by National Institute of Deafness and Other Communicative Disorders Grant RO1 DC03190 (M.B.L.); and by Regeneron Pharmaceuticals, Inc.

Keywords:

  • brain-derived neurotrophic factor
  • cell proliferation
  • forebrain parenchyma
  • intraventricular infusion
  • postnatal neurogenesis
  • subventricular zone

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

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Journal Title:

Journal of Neuroscience Nursing

Volume:

Volume 21, Number 17

Publisher:

, Pages 6706-6717

Type of Work:

Article | Final Publisher PDF

Abstract:

The findings that brain-derived neurotrophic factor (BDNF) promotes in vitro the survival and/or differentiation of postnatal subventricular zone (SVZ) progenitor cells and increasesin vivo 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.

Copyright information:

Copyright © 2001 Society for Neuroscience

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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