Evidence of newly generated neurons in the human olfactory bulb

Brain Res Dev Brain Res. 2004 Jul 19;151(1-2):159-68. doi: 10.1016/j.devbrainres.2004.03.021.


The subventricular zone (SVZ) is known to be the major source of neural stem cells in the adult brain. In rodents and nonhuman primates, many neuroblasts generated in the SVZ migrate in chains along the rostral migratory stream (RMS) to populate the olfactory bulb (OB) with new granular and periglomerular interneurons. In order to know if such a phenomenon exists in the adult human brain, we applied single and double immunostaining procedures to olfactory bulbs obtained following brain necropsy in normal adult human subjects. Double immunofluorescence labelling with a confocal microscope served to visualize cells that express markers of proliferation and immature neuronal state as well as markers that are specific to olfactory interneurons. Newborn cells that express cell cycle proteins [Ki-67, proliferating cell nuclear antigen (PCNA)] were detected in the granular and glomerular layers (GLs) of the human olfactory bulb; these cells coexpressed markers of immature neuronal state, such as Doublecortin (DCX), NeuroD and Nestin. Numerous differentiating cells expressed molecular markers of early committed neurons [beta-tubulin class III (TuJ1)] and were also immunoreactive for glutamic acid decarboxylase (GAD), a marker of GABAergic neurons, or tyrosine hydroxylase (TH), a marker of dopaminergic neurons. Other early committed neurons expressed the calcium-binding proteins calretinin (CR) or parvalbumin (PV). These results provide strong evidence for the existence of adult neurogenesis in the human olfactory system. Despite its relatively small size compared to that in rodents and nonhuman primates, the olfactory bulb in humans appears to be populated, throughout life, by new granular and periglomerular neurons that express a wide variety of chemical phenotypes.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Alcohol Oxidoreductases / metabolism
  • Basic Helix-Loop-Helix Transcription Factors
  • Calbindin 2
  • Cell Division
  • Female
  • Glutamate Decarboxylase / metabolism
  • Humans
  • Immunohistochemistry / methods
  • Intermediate Filament Proteins / metabolism
  • Isoenzymes / metabolism
  • Ki-67 Antigen / metabolism
  • Male
  • Middle Aged
  • Nerve Tissue Proteins / metabolism
  • Nestin
  • Neural Cell Adhesion Molecule L1 / metabolism
  • Neurons / metabolism*
  • Olfactory Bulb / cytology*
  • Parvalbumins / metabolism
  • Postmortem Changes
  • Proliferating Cell Nuclear Antigen / metabolism
  • S100 Calcium Binding Protein G / metabolism
  • Sialic Acids / metabolism
  • Sugar Alcohol Dehydrogenases*
  • Tubulin / metabolism
  • Tyrosine 3-Monooxygenase / metabolism


  • Basic Helix-Loop-Helix Transcription Factors
  • CALB2 protein, human
  • Calb2 protein, mouse
  • Calbindin 2
  • Intermediate Filament Proteins
  • Isoenzymes
  • Ki-67 Antigen
  • NES protein, human
  • Nerve Tissue Proteins
  • Nes protein, mouse
  • Nestin
  • Neural Cell Adhesion Molecule L1
  • Parvalbumins
  • Proliferating Cell Nuclear Antigen
  • S100 Calcium Binding Protein G
  • Sialic Acids
  • Tubulin
  • beta3 tubulin, mouse
  • polysialyl neural cell adhesion molecule
  • NeuroD protein
  • Alcohol Oxidoreductases
  • Sugar Alcohol Dehydrogenases
  • L-xylulose reductase
  • Tyrosine 3-Monooxygenase
  • Glutamate Decarboxylase
  • glutamate decarboxylase 1
  • glutamate decarboxylase 2