Evidence of newly generated neurons in the human olfactory bulb

• Published in: Brain research. Developmental brain research Vol. 151; no. 1; pp. 159 - 168
• Main Authors: Bédard, Andréanne, Parent, André
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 19.07.2004
• Subjects: Adult; Adult neurogenesis; Aged; Alcohol Oxidoreductases - metabolism; Basic Helix-Loop-Helix Transcription Factors; Brain development; Calbindin 2; Cell Division; Female; Glutamate Decarboxylase - metabolism; Human brain; 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; Olfactory system; Parvalbumins - metabolism; Postmortem Changes; Primates; Proliferating Cell Nuclear Antigen - metabolism; Rostral migratory stream; S100 Calcium Binding Protein G - metabolism; Sialic Acids - metabolism; Stem cell; Sugar Alcohol Dehydrogenases; Tubulin - metabolism; Tyrosine 3-Monooxygenase - metabolism; EPL; Rostral migratory stream; PCNA; Adult neurogenesis; Stem cell; PV; Brain development; LV; ONL; Olfactory system; OB; SVZ; Human brain; OP; GL; Sensory systems; Olfactory senses; GAD; CR; GFAP; TuJ1; GCL; TH; MCL; DCX; RMS; PSA-NCAM
• ISSN: 0165-3806
• 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 [β-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.