Hippocampal cytochrome P450s synthesize brain neurosteroids which are paracrine neuromodulators of synaptic signal transduction

Keisuke Shibuya, Norio Takata, Yasushi Hojo, Aizo Furukawa, Nobuaki Yasumatsu, Tetsuya Kimoto, Taihei Enami, Kumiko Suzuki, Nobuaki Tanabe, Hirotaka Ishii, Hideo Mukai, Taiki Takahashi, Taka aki Hattori, Suguru Kawato

Research output: Contribution to journalArticlepeer-review

119 Citations (Scopus)

Abstract

Hippocampal pyramidal neurons and granule neurons of adult male rats are equipped with a complete machinery for the synthesis of pregnenolone, dehydroepiandrosterone, 17β-estradiol and testosterone as well as their sulfate esters. These brain neurosteroids are synthesized by cytochrome P450s (P450scc, P45017α and P450arom) from endogenous cholesterol. Synthesis is acutely dependent on the Ca2+ influx attendant upon neuron-neuron communication via N-methyl-D-aspartate (NMDA) receptors. Pregnenolone sulfate, estradiol and corticosterone rapidly modulate neuronal signal transduction and the induction of long-term potentiation via NMDA receptors and putative membrane steroid receptors. Brain neurosteroids are therefore promising neuromodulators that may either activate or inactivate neuron-neuron communication, thereby mediating learning and memory in the hippocampus.

Original languageEnglish
Pages (from-to)301-316
Number of pages16
JournalBiochimica et Biophysica Acta - General Subjects
Volume1619
Issue number3
DOIs
Publication statusPublished - 2003 Feb 17
Externally publishedYes

Keywords

  • Brain
  • Hippocampus
  • LTP
  • Neurosteroid
  • P450
  • Signal transduction

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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