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Retinoic acid receptor-dependent survival of olfactory sensory neurons in postnatal and adult mice.
Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). (Bohm)
Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet). (Berghard)
Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). (Bohm)
2006 (Engelska)Ingår i: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 26, nr 12, s. 3281-3291Artikel i tidskrift (Refereegranskat) Published
Ort, förlag, år, upplaga, sidor
2006. Vol. 26, nr 12, s. 3281-3291
Identifikatorer
URN: urn:nbn:se:umu:diva-16510DOI: 10.1523/JNEUROSCI.4955-05.2006PubMedID: 16554478OAI: oai:DiVA.org:umu-16510DiVA, id: diva2:156183
Tillgänglig från: 2007-10-04 Skapad: 2007-10-04 Senast uppdaterad: 2018-06-09
Ingår i avhandling
1. Effects of retinoic acid in the mouse olfactory sensory systems
Öppna denna publikation i ny flik eller fönster >>Effects of retinoic acid in the mouse olfactory sensory systems
2007 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

A common characteristic in neurodegenerative diseases of the brain is death of specific neuronal populations. The lack of neuron proliferation and axon extension in most parts of the central nervous system leads to chronic loss of neurons in the case of injury or disease. Therefore it is essential to identify signals involved in neurogenesis and neuronal survival. A favorable model in which to study these events is the olfactory sensory neurons in the main olfactory epithelium and their target in the glomeruli of the olfactory bulb.

In spite of constant regeneration, each olfactory sensory neuron maintain expression of one particular odorant receptor and the specificity of their axonal projections to the glomeruli. Most mammals also have an accessory olfactory system consisting of the sensory neurons in the vomeronasal epithelium and their target area the accessory olfactory bulb. Differential expression of receptors and other genes divides the olfactory and vomeronasal epithelium into zones, but the function and mechanisms underlying the establishment of these zones are still elusive.

We identified four genes with graded expression patterns that correlated with the zones of the olfactory epithelium. One of the identified genes encodes a retinoic acid synthesizing enzyme, RALDH-2. We showed that RALDH-2 was expressed in a gradient in cells of the lamina propria underneath the olfactory epithelium, suggesting a possible retinoic acid regulation of zonally expressed genes in the olfactory epithelium.

To investigate the role of retinoic acid in the olfactory systems, we generated a transgenic mouse strain that selectively expressed a dominant negative retinoic acid receptor in mature olfactory and vomeronasal neurons. We found that subsequent to the establishment of axonal projections, the neurons of both olfactory systems died prematurely by retrograde caspase-3 activation. In the main olfactory system the onset of apoptosis was associated with the appearance of incorrect heterogenous glomeruli with axons of more than one OR identity. Additionally, the activity regulated cell adhesion molecule kirrel-2 was down regulated suggesting an additional regulation of this gene by retinoic acid. Deficient retinoic acid signaling in olfactory sensory neurons could thus induce apoptosis by changing the parameters for axonal competition by neural activity and kirrel-2 expression.

We found evidence for a selective neuronal death in the accessory olfactory system of the dnRAR mice, where only vomeronasal sensory neurons belonging to the basal zone died by retrograde caspase-3 activation. This implies that the two populations of sensory neurons in the vomeronasal epithelium differently depend on retinoic acid for their survival.

Ort, förlag, år, upplaga, sidor
Umeå: Molekylärbiologi (Medicinska fakulteten), 2007. s. 63
Serie
Umeå University medical dissertations, ISSN 0346-6612 ; 1124
Nyckelord
olfactory, retinoic acid, neuron survival
Nationell ämneskategori
Biokemi och molekylärbiologi
Identifikatorer
urn:nbn:se:umu:diva-1371 (URN)978-91-7264-375-8 (ISBN)
Disputation
2007-10-12, Major Groove, 6L, NUS, Umeå, 13:00 (Engelska)
Opponent
Handledare
Tillgänglig från: 2007-09-26 Skapad: 2007-09-26 Senast uppdaterad: 2009-05-25Bibliografiskt granskad

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Berghard, AnnaBohm, Staffan

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Institutionen för molekylärbiologi (Medicinska fakulteten)Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet)
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Totalt: 194 träffar
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