Loss of STOP protein impairs peripheral olfactory neurogenesis.
BACKGROUND
STOP (Stable Tubulin-Only Polypeptide) null mice show behavioral deficits, impaired synaptic plasticity, decrease in synaptic vesicular pools and disturbances in dopaminergic transmission, and are considered a neurodevelopmental model of schizophrenia. Olfactory neurons highly express STOP protein and are continually generated throughout life. Experimentally-induced loss of olfactory neurons leads to epithelial regeneration within two months, providing a useful model to evaluate the role played by STOP protein in adult olfactory neurogenesis.


RESULTS
Immunocytochemistry and electron microscopy were used to study the structure of the glomerulus in the main olfactory bulb and neurogenesis in the neurosensorial epithelia. In STOP null mice, olfactory neurons showed presynaptic swellings with tubulovesicular profiles and autophagic-like structures. In olfactory and vomeronasal epithelia, there was an increase in neurons turnover, as shown by the increase in number of proliferating, apoptotic and immature cells with no changes in the number of mature neurons. Similar alterations in peripheral olfactory neurogenesis have been previously described in schizophrenia patients. In STOP null mice, regeneration of the olfactory epithelium did not modify these anomalies; moreover, regeneration resulted in abnormal organisation of olfactory terminals within the olfactory glomeruli in STOP null mice.


CONCLUSIONS
In conclusion, STOP protein seems to be involved in the establishment of synapses in the olfactory glomerulus. Our results indicate that the olfactory system of STOP null mice is a well-suited experimental model (1) for the study of the mechanism of action of STOP protein in synaptic function/plasticity and (2) for pathophysiological studies of the mechanisms of altered neuronal connections in schizophrenia.
Benardais
Karelle
K
INSERM U666, Strasbourg, France.
Kasem
Basem
B
Couegnas
Alice
A
Samama
Brigitte
B
Fernandez
Sebastien
S
Schaeffer
Christiane
C
Antal
Maria-Cristina
MC
Job
Didier
D
Schweitzer
Annie
A
Andrieux
Annie
A
Giersch
Anne
A
Nehlig
Astrid
A
Boehm
Nelly
N
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000172:deficiency* / Q000235:genetics; D055495:Neurogenesis; D009830:Olfactory Bulb / Q000166:cytology / Q000378:metabolism; D009831:Olfactory Mucosa / Q000294:innervation / Q000378:metabolism; D018034:Olfactory Receptor Neurons / Q000378:metabolism*; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism; D013569:Synapses / Q000378:metabolism
D008869:Microtubule-Associated Proteins; C491893:Mtap6 protein, mouse