Vitamin A Deficiency Leads to Increased Cell Proliferation in Olfactory Epithelium of Mature Rats

J Neurobiol. 2003 Mar;54(4):539-54. doi: 10.1002/neu.10192.


We have shown previously that vitamin A deficiency (VAD) leads to the decreased expression of gene products that are specifically synthesized by mature neurons in the olfactory epithelium (OE) of adult rats. These results support the hypothesis that retinoic acid, a derivative of vitamin A, is required for neurogenesis and neuron replacement in vivo. VAD does not cause gross degeneration of the OE, raising the question: what types of cells continue to populate VAD OE? In this study, we compared the cell densities of VAD and VA-sufficient (VAS) OE and investigated whether cell proliferation is upregulated in VAD OE. The results show that (1) total cell number in VAD and VAS OE are comparable; (2) localized areas of hyperplasia are present in the basal regions of VAD, but not VAS, OE; (3) there is a substantial increase in the number of PCNA (proliferating cell nuclear antigen) positive cells in the basal region of VAD OE relative to VAS OE; and (4) there is a relative increase in the levels of mRNA encoding the transcription factor, MASH I, in VAD OE. We conclude that reduced availability of vitamin A derivatives, such as retinoic acid, leads to a loss of control over proliferation, hyperplasia, and increased numbers of pro-neural cells in vivo.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Newborn / growth & development
  • Basic Helix-Loop-Helix Transcription Factors
  • Cell Count / methods
  • Cell Division / physiology
  • DNA-Binding Proteins / metabolism
  • Immunohistochemistry
  • In Situ Hybridization / methods
  • Male
  • Nerve Tissue Proteins / metabolism
  • Olfactory Marker Protein
  • Olfactory Mucosa / metabolism
  • Olfactory Mucosa / pathology*
  • Proliferating Cell Nuclear Antigen / metabolism
  • RNA, Messenger / biosynthesis
  • RNA, Ribosomal, 18S / metabolism
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors / metabolism
  • Vitamin A Deficiency / metabolism*
  • Vitamin A Deficiency / pathology*


  • Ascl1 protein, rat
  • Basic Helix-Loop-Helix Transcription Factors
  • DNA-Binding Proteins
  • Nerve Tissue Proteins
  • Olfactory Marker Protein
  • Omp protein, rat
  • Proliferating Cell Nuclear Antigen
  • RNA, Messenger
  • RNA, Ribosomal, 18S
  • Transcription Factors