Expression and p75 neurotrophin receptor dependence of cholesterol synthetic enzymes in adult mouse brain

Zeljka Korade, Zhiping Mi, Carmel Portugal, Nina F. Schor

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


Normal brain function depends critically on cholesterol. Although cholesterol is synthesized locally in the adult brain, the precise anatomical localization of cholesterogenic enzymes is not known. Here we show that 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoAred) and 7-dehydrocholesterol reductase (7dhcred), the first and last enzymes, respectively, in the cholesterol biosynthesis pathway, are co-expressed in neurons throughout adult murine brain. Co-localization is most prominent in cortical, hippocampal, and cholinergic neurons. Since adult hippocampal and cholinoergic neurons express p75 neurotrophin receptors (p75NTR) we hypothesized that p75NTR regulates expression of cholesterogenic enzymes. Treatment of Neuro2a neuroblastoma cells or primary cerebellar cultures with siRNA downregulates p75NTR and decreases the expression level of HMG-CoAred and 7dhcred. Native neuroblastoma cell lines with differential expression of p75NTR differentially express 7dhcred; 7dhcred expression correlates with p75NTR expression. This suggests that, in p75NTR-expressing cells, p75NTR regulates cholesterol synthesis through regulation of HMG-CoAred and 7dhcred expression. The unexpected localization of cholesterogenic enzymes in adult neurons suggests that at least some adult neurons retain the ability to synthesize cholesterol.

Original languageEnglish (US)
Pages (from-to)1522-1531
Number of pages10
JournalNeurobiology of Aging
Issue number10
StatePublished - Oct 2007
Externally publishedYes


  • 7dhcred
  • Cholesterol
  • HMG-CoAred
  • In situ hybridization
  • P75 neurotrophin receptor

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Developmental Biology
  • Clinical Neurology
  • Geriatrics and Gerontology


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