Induction of the serotonin1A receptor in neuronal cells during prolonged stress and degeneration

Jyoti K. Singh, Brett A. Chromy, Michael J. Boyers, Glyn Dawson, Probal Banerjee

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

Neuronal migration in brain is followed by differentiation of committed neurons and simultaneous apoptosis of uncommitted preneuronal cells due to a limiting supply of trophic factors and nutrients. We have dissected differentiation and apoptosis by designing a simple in vitro model for this nutrient deprivation using engineered neuronal cell lines stably transfected with a promoterless segment (G-21) of the intronless human serotonin1A receptor (5-HT1A-R) gene. Despite the use of widely different heterologous promoters (cytomegalovirus and Rous sarcoma virus) for the stable expression of G-21, a dramatic increase in expression of the 5-HT1A-R (five- to 15-fold) and its mRNA was always observed during degeneration and apoptosis of nutrient-deprived neuronal cells. Involvement in this induction of a 170-bp 5′-end untranslated sequence (5′-UT) (tail end of the 500-bp natural promoter) of G-21 was confirmed by stable transfection of neuronal cells with an SV-40 promoter-driven construct harboring the 5′-UT and the reporter chloramphenicol acetyltransferase (CAT) cDNA. Presence of the 5′-UT resulted in a threefold increase in CAT expression during nutrient deprivation in randomly chosen clones. The induction was also observed in the endogenous 5-HT1A-R, expressed by embryonic day 16 mouse hippocampal neurons, subsequent to nutrient deprivation and onset of degeneration. A trophic role of the 5-HT1A-R has been suggested in earlier studies. Considering the example of protective heat shock proteins, which are induced during various types of stress, our results suggest that stressed neuronal cells undergoing degeneration and apoptosis synthesize increased levels of 5-HT1A-R as a final attempt to survive.

Original languageEnglish (US)
Pages (from-to)2361-2372
Number of pages12
JournalJournal of Neurochemistry
Volume66
Issue number6
StatePublished - Jun 1996
Externally publishedYes

Keywords

  • Neuronal cells
  • Serotonin 5-HT receptor
  • Stress regulation

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Induction of the serotonin<sub>1A</sub> receptor in neuronal cells during prolonged stress and degeneration'. Together they form a unique fingerprint.

  • Cite this

    Singh, J. K., Chromy, B. A., Boyers, M. J., Dawson, G., & Banerjee, P. (1996). Induction of the serotonin1A receptor in neuronal cells during prolonged stress and degeneration. Journal of Neurochemistry, 66(6), 2361-2372.