BDNF up-regulates pre-pro-TRH mRNA expression in the fetal/neonatal paraventricular nucleus of the hypothalamus. Properties of the transduction pathway

Raimundo Ubieta, Rosa Maria Uribe, José Antonio González, Arlene García-Vázquez, Carlos Pérez-Monter, Leonor Pérez-Martínez, Patricia Joseph-Bravo, Jean-Louis Charli

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18 Citations (Scopus)


Brain derived neurotrophic factor (BDNF) increases the levels of pre-pro-thyrotropin releasing hormone (TRH) mRNA in fetal rodent hypothalamic neurons that express TrkB receptors. The present studies aimed at better understanding the role of BDNF in establishing and maintaining the TRH phenotype in hypothalamic neurons during early development. To determine where BDNF regulates the expression of pre-pro-TRH mRNA in vivo, we compared the hypothalamic distribution of pre-pro-TRH mRNA to that of TrkB mRNA. Full-length TrkB (FL-TrkB) mRNA was detected earlier in development than pre-pro-TRH mRNA in the region that gives rise to the paraventricular nucleus of the hypothalamus (PVN). We also evaluated the effects of BDNF on the expression of pre-pro-TRH mRNA in vitro. BDNF up-regulated the levels of pre-pro-TRH mRNA in primary cell cultures obtained from the hypothalamus or the PVN of 17 days old fetuses or newborn rats. This effect was abolished by PD98059, an inhibitor of the mitogen-activated protein kinase kinase (MEK) 1/2 or 5. The effect of BDNF on pre-pro-TRH mRNA levels was reversible. The continuous application of BDNF led to a desensitization of the response at day 10 in vitro, an effect that correlated with a drop in the levels of FL-TrkB protein. In conclusion, BDNF enhances the expression of pre-pro-TRH mRNA in PVN neurons. This effect is reversible, decreases with time, and requires an active MEK. BDNF may contribute to the enhancement of pre-pro-TRH mRNA expression in the hypothalamic PVN during development.

Original languageEnglish
Pages (from-to)28-38
Number of pages11
JournalBrain Research
Publication statusPublished - 12 Oct 2007

Bibliographical note

The authors thank F. Romero and M. Villa for technical assistance and S. González for providing the animals used in this study. Supported in part by DGAPA-UNAM grants # IN 223599 and 227002-3 as well as CONACYT Mexico–Cuba Program.


  • Animals
  • Animals, Newborn
  • Brain-Derived Neurotrophic Factor
  • Carcinoma, Medullary
  • Female
  • Gene Expression Regulation, Developmental
  • Hypothalamus
  • Male
  • Neurons
  • Paraventricular Hypothalamic Nucleus
  • Pregnancy
  • Protein Precursors
  • RNA, Messenger
  • Rats
  • Rats, Wistar
  • Receptor, trkB
  • Signal Transduction
  • Thyroid Neoplasms
  • Thyrotropin-Releasing Hormone
  • Tumor Cells, Cultured
  • Journal Article
  • Research Support, Non-U.S. Gov't


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