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Furthermore, multiple families of proteins can bind to the
extracellular region of Neogenin including Netrins, Repulsive
Guidance Molecules (RGM), and Bone Morphogenetic Proteins
(BMP). Using in situ hybridization and immunohistochemical
approaches, we have examined the pattern of expression of
Neogenin and of its ligands in the OE. Our analyses have revealed
that Neogenin is expressed at high levels in the basal progenitor
cell region of the OE and in mature OSNs. In contrast, expression
of the Neogenin ligand, RGM-b, is restricted to immature OSNs.
These patterns of expression suggest that RGM-b-Neogenin
interactions may regulate the differentiation of progenitor cells into
OSNs. To test this hypothesis, we have examined the development
of OSNs in Neogenin mutant mice. Ablation of Neogenin
expression leads to an increase in the number of proliferating cells
in the basal region of the OE, and to a decrease in the number of
mature OSNs, indicating that Neogenin regulates the differentiation
of progenitor cells into OSNs. We are currently assessing the role
of RGM-b in this process by using a combination of
in vitro
and
in
vivo
approaches. Our findings therefore define a new role for
Neogenin in olfactory neurogenesis. Acknowledgements: Canadian
Institute of Health Research
#P89
POSTER SESSION III:
OLFACTION DEVELOPMENT & CNS;
HUMAN PSYCHOPHYSICS; TASTE PERIPHERY
IS OLFACTORY NEURAL STEMACTIVITY PERTURBED
IN ALZHEIMER’S DISEASE?
Athena Chou, Connor Keller, Nicole Janzen, Jane A. Roskams
Department of Zoology, Life Sciences Centre, UBC, 2350 Health
Sciences Mall Vancouver, BC, Canada
Despite the extensive neurogenic capacity of the olfactory system,
it is not able to maintain function during the progression of
Alzheimer’s disease (AD) and, in fact, shows some of the earliest
AD deficits. So, do olfactory neural stem cells (NSCs) in the
Olfactory Epithelium (OE) or subventricular zone (SVZ) become
dysregulated in their ability to compensate for loss of neuronal
function in AD? Familial AD is linked to mutations in Amyloid
Precursor Protein (APP) and Presenilins 1 and 2. APP mutations
can increase apoptosis of Olfactory Receptor Neurons (ORNs),
which should produce a compensatory up-regulation in
neurogenesis. However, presenilin mutations could impact the
stability of NSCs, or ability of ORNs to be assisted in targeting by
Olfactory Ensheathing cells, due to deficits in Notch signaling. This
has lead us to test if the olfactory system develops early signs of
AD as a result of the failure to maintain neurogenesis from its NSC
pools, in human AD post-mortem SVZ, and the OE and SVZ of a
symptomatic mouse AD model. To test for the integrity of the NSC
niche in human AD, we have developed new techniques to detect
human NSC and progenitor markers (including GFAP, GFAPδ,
BLBP, Vimentin, PSA-NCAM) in formalin-fixed AD SVZ. We
reveal a subpopulation of GFAP
+
potential progenitors in the
human AD SVZ expressing GFAPδ and BLBP, and that the
proliferation index of distinct potential progenitors in the SVZ is
variable between AD patients. We are now using multiple
thymidine labels and in vitro assays to test if distinct changes in
neurogenic capacity and progenitor activity occur from 3-12
months in the SVZ and OE of the PS1/APPSwe doubt Tg mouse
model of AD. Our results indicate a potential disruption in the
maintenance and activity of progenitors that are direct targets of
Notch regulation. Acknowledgements: The Pacific Alzheimer’s
Research Fund, the Jack Brown family Foundation (to JR) and a
Canadian Institutes of Health Research studentship (To AC).
#P90
POSTER SESSION III:
OLFACTION DEVELOPMENT & CNS;
HUMAN PSYCHOPHYSICS; TASTE PERIPHERY
Functional and Molecular Characterization of the Cell
Turnover in the Olfactory System
Ivan Manzini
1,2
, Josua Kuttler
1
, Thomas Hassenklöver
1,2
1
Institute of Physiology, Neurophysiology and Cellular Biophysics
Göttingen, Germany,
2
DFG Research Center for Molecular
Physiology of the Brain (CMPB) Göttingen, Germany
In the olfactory system continuous cell turnover takes place
throughout life, making this system to one of the most plastic
regions of the brain. In the olfactory epithelium there is a constant
replacement of olfactory receptor neurons, while in the olfactory
bulb new neurons are continuously integrated into an existing
neuronal circuitry. The new olfactory receptor neurons originate
from a neurogenic zone residing in the most basal part of the
epithelium, the new neurons of the olfactory bulb originate from a
neurogenic zone lining the lateral telencephalic ventricles. The
maintenance of a functional sense of smell requires a fine-tuned
and highly regulated interplay of apoptosis, neurogenesis and
neuronal integration. Among many other factors, nucleotides and
their receptors have been shown to play an important role in the
regulation of neurogenesis during embryonic development as well
as in the adult nervous system. Here we have characterized the
purinergic system of the olfactory epithelium and the anterior
telencephalon of larval
Xenopus laevis
and found that extracellular
nucleotides, acting via a multitude of purinergic receptors, play an
essential role in the fine-tuning of the cell turnover in the olfactory
system. Using calcium imaging, functional apoptosis detection in
acute tissue slices and immunohistochemistry, we were able to
show the involvement of purinergic signaling in the regulation of
apoptosis and neurogenesis in both, the olfactory epithelium and
the olfactory bulb. The outcome of the present work is a further
step in an effort to understand the so far only poorly understood
mechanisms regulating the cell turnover in the olfactory system.
Acknowledgements: Supported by DFG CMPB (Project B1/9)
to I.M. and DFG Schwerpunktprogramm 1392 (project MA
4113/2-1) to I.M.
#P91
POSTER SESSION III:
OLFACTION DEVELOPMENT & CNS;
HUMAN PSYCHOPHYSICS; TASTE PERIPHERY
Effect of Vitamin A Deficiency on Olfactory Marker Protein
Expression in Postnatal Mouse Olfactory Neurons
Bukola A Oke, Mary Ann Asson-Batres
Tennessee State University Nashville, TN, USA
Previous studies in our lab have shown dietary deficiency in
vitamin A (VAD) is associated with decreased numbers of mature
olfactory receptor neurons (ORNs) in the postnatal rat olfactory
epithelium. We questioned whether a similar effect would be
observed in mice. Because mice are more difficult to make VAD,
we elected to use a mouse with a mutated lecithin retinyl acyl
transferase (LRAT knockout, KO) gene for these studies. Others
have shown that essentially all retinol stores are depleted in LRAT
mice fed a VAD diet for one month. We set up studies to determine
VAD effects on mice, specifically, on ORN numbers. LRAT KO
age-matched, males were fed a VAD diet or a diet supplemented
with VA (VAS) for 8 weeks (Study 1) or 19 weeks (Study 2).
Studies included age matched, male wild type (WT) VAS control
groups. Whereas VAD rats exhibit distinct signs of VAD that
include alopecia, ataxia, reddened eyes, white teeth and decreased
Abstracts | 57
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