Co-localization of brain-derived neurotrophic factor (BDNF) and wild-type huntingtin in normal and quinolinic acid-lesioned rat brain

Francesca R. Fusco, Chiara Zuccato, Marzia Tartari, Alessandro Martorana, Zena De March, Carmela Giampà, Elena Cattaneo, Giorgio Bernardi

Research output: Contribution to journalArticlepeer-review

Abstract

Loss of huntingtin-mediated brain-derived neurotrophic factor (BDNF) gene transcription has been described in Huntington's disease (HD) [Zuccato et al. (2001) Science, 293, 493-498]. It has been shown that BDNF is synthesized in the pyramidal layer of cerebral cortex and released in the striatum [Altar et al (1997) Nature, 389, 856-860; Conner et al (1997) J. Neurosci., 17, 2295-2313]. Here we show the cellular localization of BDNF in huntingtin-containing neurons in normal rat brain; our double-label immunofluorescence study shows that huntingtin and BDNF are co-contained in ≈99% of pyramidal neurons of motor cortex. In the striatum, huntingtin is expressed in 75% of neurons containing BDNF. In normal striatum we also show that BDNF is contained in cholinergic and in NOS-containing interneurons, which are relatively resistant to HD degeneration. Furthermore, we show a reduction in huntingtin and in BDNF immunoreactivity in cortical neurons after striatal excitotoxic lesion. Our data are confirmed by an ELISA study of BDNF and by a Western blot analysis of huntingtin in cortex of quinolic acid (QUIN)-lesioned hemispheres. In the lesioned striatum we describe that the striatal subpopulation of cholinergic neurons, surviving degeneration, contain BDNF. The finding that BDNF is contained in nearly all neurons that contain huntingtin in the normal cortex, along with the reduced expression of BDNF after QUIN injection of the striatum, shows that huntingtin may be required for BDNF production in cortex.

Original languageEnglish
Pages (from-to)1093-1102
Number of pages10
JournalEuropean Journal of Neuroscience
Volume18
Issue number5
DOIs
Publication statusPublished - Sep 2003

Keywords

  • Cortico-striatal inputs
  • ELISA
  • Huntington's disease
  • Immunofluorescence

ASJC Scopus subject areas

  • Neuroscience(all)

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