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ARTICLE, Development/Plasticity/Repair

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

Viorica Pencea, Kimberly D. Bingaman, Stanley J. Wiegand and Marla B. Luskin
Journal of Neuroscience 1 September 2001, 21 (17) 6706-6717; DOI: https://doi.org/10.1523/JNEUROSCI.21-17-06706.2001
Viorica Pencea
1Departments of Cell Biology and
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Kimberly D. Bingaman
1Departments of Cell Biology and
2Neurosurgery, Emory University School of Medicine, Atlanta, Georgia 30322, and
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Stanley J. Wiegand
3Regeneron Pharmaceuticals Inc., Tarrytown, New York 10591
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Marla B. Luskin
1Departments of Cell Biology and
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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.

  • brain-derived neurotrophic factor
  • cell proliferation
  • forebrain parenchyma
  • intraventricular infusion
  • postnatal neurogenesis
  • subventricular zone
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The Journal of Neuroscience: 21 (17)
Journal of Neuroscience
Vol. 21, Issue 17
1 Sep 2001
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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
Viorica Pencea, Kimberly D. Bingaman, Stanley J. Wiegand, Marla B. Luskin
Journal of Neuroscience 1 September 2001, 21 (17) 6706-6717; DOI: 10.1523/JNEUROSCI.21-17-06706.2001

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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
Viorica Pencea, Kimberly D. Bingaman, Stanley J. Wiegand, Marla B. Luskin
Journal of Neuroscience 1 September 2001, 21 (17) 6706-6717; DOI: 10.1523/JNEUROSCI.21-17-06706.2001
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Keywords

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

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