5,19-cyclo-9β,10ξ-androstane-3,17-dione promotes neurotrophic factor biosynthesis in 1321N1 human astrocytoma cells and improves passive avoidance learning impairment

Yutaro Obara, Asami Haganuma, Shinsuke Murakami, Toshiki Chiba, Koichiro Mori, Osamu Nakagawasai, Takeshi Tadano, Haruhisa Kikuchi, Yoshiteru Oshima, Norimichi Nakahata

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Since neurotrophic factors are essential for neurons to form neuronal networks and maintain neuronal functions, neurotrophic factor-like substances or inducers of neurotrophic factors can be useful for the treatment of serious neuronal diseases such as Alzheimer's and Parkinson's diseases. In the present study, we examined an effect of 5,19-cyclo-9β,10ξ-androstane-3,17-dione (CAD) on neurotrophic factor synthesis in glial cells and scopolamine-induced impairment of learning in mice. 1321N1 human astrocytoma cells promoted secretion of certain neurotrophic factors in response to CAD with no cytotoxicity, which caused dramatic neurite outgrowth in rat pheochromocytoma (PC12) cells. In fact, CAD significantly enhanced nerve growth factor (NGF) secretion and its gene expression in 1321N1 cells, in a time and concentration-dependent manner. Because second messengers such as cAMP, inositol 1,4,5-trisphosphates and Ca2+ induce NGF gene expression, we measured activities of adenylyl cyclase and phospholipase C and intracellular Ca2+ concentration in 1321N1 cells. However, CAD changed neither second messenger levels. CAD enhanced the gene expression of proto-oncogene, c-fos that is one of the components of transcription factor (AP-1). In addition to those above, the in vivo effects of CAD were also examined. Although injection of muscarinic receptor antagonist scopolamine impaired passive avoidance learning in mice, pretreatment with CAD significantly reversed the adverse effect in a dose-dependent manner. Taking these results together, CAD has enormous therapeutic potential for serious neuronal diseases.

Original languageEnglish
Pages (from-to)57-64
Number of pages8
JournalBrain research
Volume1184
Issue number1
DOIs
Publication statusPublished - 2007 Dec 12

Keywords

  • 1321N1 human astrocytoma cell
  • 5,19-cyclo-9β,10ξ-androstane-3,17-dione (CAD)
  • Nerve growth factor (NGF)
  • Neurotrophic factor
  • PC12 cell

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology

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