Double recording system of Period1 gene expression rhythm in the olfactory bulb and liver in freely moving mouse.

Clock genes express circadian rhythms in most organs. These rhythms are organized throughout the whole body, regulated by the suprachiasmatic nucleus (SCN) in the brain. Disturbance of these clock gene expression rhythms is a risk factor for diseases such as obesity and cancer. To understand the mechanism of regulating clock gene expression rhythms in vivo, multiple real time recording systems are required. In the present study, we developed a double recording system of Period1 expression rhythm in peripheral tissue (liver) and the brain. In peripheral tissue, quantification of gene expression in a steadily moving target was achieved by using a photomultiplier tube (PMT) attached to a tissue contact optical sensor (TCS). Using this technique, we were able to analyze circadian rhythms of clock gene expression over a prolonged period in the liver and olfactory bub (OB) of the brain. The present double recording system has no effect on behavioral activity or rhythm. Our novel system thus successfully quantifies clock gene expression in deep areas of the body in freely moving mice for a period sufficient to analyze circadian dynamics. In addition, our double recording system can be widely applied to many areas of biomedical research, as well as applications beyond medicine.

Dynamic changes in cytoskeleton proteins of olfactory ensheathing cells induced by radiofrequency electromagnetic fields.

Several evidences have suggested the ability of radiofrequency electromagnetic fields to influence biological systems, even if the action mechanisms are not well understood. There are few data on the effect of radiofrequency electromagnetic fields on self-renewal of neural progenitor cells. A particular glial type that shows characteristics of stem cells is olfactory ensheathing cells (OECs). Herein, we assessed the non-thermal effects induced on OECs through radiofrequency electromagnetic fields changing the envelope of the electromagnetic wave. Primary OEC cultures were exposed to continuous or amplitude-modulated 900 MHz electromagnetic fields, in the far-field condition and at different exposure times (10, 15, 20 min). The expression of OEC markers (S-100 and nestin), cytoskeletal proteins (GFAP and vimentin), apoptotic pathway activation by caspase-3 cleavage and cell viability were evaluated. Our results highlight that 20 min of exposure to continuous or amplitude-modulated 900 MHz electromagnetic fields induced a different and significant decrease in cell viability. In addition, according to the electromagnetic field waveform, diverse dynamic changes in the expression of the analysed markers in OECs and activation of the apoptotic pathway were observed. The data suggest that radiofrequency electromagnetic fields might play different and important roles in the self-renewal of OEC stem cells, which are involved in nervous system repair.

Inhibiting constitutive neurogenesis compromises long-term social recognition memory.

Although the functional role for newborn neurons in neural circuits is still matter of investigation, there is no doubt that neurogenesis modulates learning and memory in rodents. In general, boosting neurogenesis before learning, using genetic-target tools or drugs, improves hippocampus-dependent memories. However, inhibiting neurogenesis may yield contradictory results depending on the type of memory evaluated. Here we tested the hypothesis that inhibiting constitutive neurogenesis would compromise social recognition memory (SRM). Male Swiss mice were submitted to three distinct procedures to inhibit neurogenesis: (1) intra-cerebral infusion of Cystosine-ß-D-Arabinofuranoside (AraC); (2) intra-peritoneal injection of temozolomide (TMZ) and (3) cranial gamma irradiation. All three methods decreased cell proliferation and neurogenesis in the dentate gyrus of the dorsal (dDG) and ventral hippocampus (vDG), and the olfactory bulb (OB). However, the percentage inhibition diverged between methods and brain regions. Ara-C, TMZ and gamma irradiation impaired SRM, though only gamma irradiation did not cause side effects on weight gain, locomotor activity and anxiety. Finally, we examined the contribution of cell proliferation in vDG, dDG and OB to SRM. The percent of inhibition in the dDG correlates with SRM, independently of the method utilized. This correlation was observed for granular cell layer of OB and vDG, only when the inhibition was induced by gamma irradiation. Animal's performance was restrained by the inhibition of dDG cell proliferation, suggesting that cell proliferation in the dDG has a greater contribution to SRM. Altogether, our results demonstrate that SRM, similarly to other hippocampus-dependent memories, has its formation impaired by reducing constitutive neurogenesis.

Perception of sniff phase in mouse olfaction.

Olfactory systems encode odours by which neurons respond and by when they respond. In mammals, every sniff evokes a precise, odour-specific sequence of activity across olfactory neurons. Likewise, in a variety of neural systems, ranging from sensory periphery to cognitive centres, neuronal activity is timed relative to sampling behaviour and/or internally generated oscillations. As in these neural systems, relative timing of activity may represent information in the olfactory system. However, there is no evidence that mammalian olfactory systems read such cues. To test whether mice perceive the timing of olfactory activation relative to the sniff cycle ('sniff phase'), we used optogenetics in gene-targeted mice to generate spatially constant, temporally controllable olfactory input. Here we show that mice can behaviourally report the sniff phase of optogenetically driven activation of olfactory sensory neurons. Furthermore, mice can discriminate between light-evoked inputs that are shifted in the sniff cycle by as little as 10 milliseconds, which is similar to the temporal precision of olfactory bulb odour responses. Electrophysiological recordings in the olfactory bulb of awake mice show that individual cells encode the timing of photoactivation in relation to the sniff in both the timing and the amplitude of their responses. Our work provides evidence that the mammalian olfactory system can read temporal patterns, and suggests that timing of activity relative to sampling behaviour is a potent cue that may enable accurate olfactory percepts to form quickly.

Postcomparison of [(18) F]-fluorodeoxyglucose uptake in the brain after short-term bright light exposure and no intervention.

OBJECTIVE: Bright light therapy is widely used as the treatment of choice for seasonal affective disorder. Nonetheless, our understanding of the mechanisms of bright light is limited and it is important to investigate the mechanisms. The purpose of this study is to examine the hypothesis that bright light exposure may increase [(18) F]-fluorodeoxyglucose (FDG) uptake in olfactory bulb and/or hippocampus which may be associated neurogenesis in the human brain. METHOD: A randomized controlled trial comparing 5-day bright light exposure + environmental light (bright light exposure group) with environmental light alone (no intervention group) was performed for 55 participants in a university hospital. The uptake of [(18) F]FDG in olfactory bulb and hippocampus using FDG positron emission tomography was compared between two groups. RESULTS: There was a significant increase of uptake in both right and left olfactory bulb for bright light exposure group vs. no intervention group. After adjustment of log-transformed illuminance, there remained a significant increase of uptake in the right olfactory bulb. CONCLUSION: The present findings suggest a possibility that 5-day bright light exposure may increase [(18) F]FDG in the right olfactory bulb of the human brain, suggesting a possibility of neurogenesis. Further studies are warranted to directly confirm this possibility.

Morphological and behavioural changes occur following the X-ray irradiation of the adult mouse olfactory neuroepithelium.

BACKGROUND: The olfactory neuroepithelium lines the upper nasal cavity and is in direct contact with the external environment and the olfactory bulbs. The ability to self-renew throughout life and the reproducible recovery after injury, make it a model tissue to study mechanisms underlying neurogenesis. In this study, X-rays were used to disrupt proliferating olfactory stem cell populations and to assess their role in the cellular and morphological changes involved in olfactory neurogenic processes. RESULTS: We have analysed the histological and functional effects of a sub-lethal dose of X-rays on the adult mouse olfactory neuroepithelium at 2 hours, 24 hours, 1 week, 2 weeks and 5 weeks. We have shown an immediate cessation of proliferating olfactory stem cells as shown by BrdU, Ki67 and pH3 expression. At 24 hours there was an increase in the neural transcription factors Mash1 and Pax6 expression, and a disruption of the basal lamina and increase in glandular cell marker expression at 1 week post-irradiation. Coincident with these changes was an impairment of the olfactory function in vivo. CONCLUSIONS: We have shown significant changes in basal cell proliferation as well as morphological changes in the olfactory neuroepithelium following X-ray irradiation. There is involvement of the basal lamina as well as a clear role for glandular and sustentacular cells.

Light responsiveness of clock genes, Per1 and Per2, in the olfactory bulb of mice.

The olfactory bulb (OB) of rodents has been suggested to possess a self-sustaining circadian oscillator which functions independent from the master circadian clock in the suprachiasmatic nucleus (SCN) of the hypothalamus. However, neither histology nor physiology of this extra-SCN clock is studied yet. In the present study, we examined circadian variation of major clock gene expressions in the OB and responsiveness to single photic stimuli. Here we show significant circadian variation in the expression of clock genes, Per1, Per2 and Bmal1 in the OB. Per1 and PER2 were mainly expressed in the mitral cell and granular cell layers of the OB. Light responsiveness of Per1 and Per2 expression was different in the OB from that in the parietal cortex. Both Per1 and Per2 are expressed in the OB only by l000 lux light pulse, whereas 100 lux light was enough to induce Per1 mRNA in the parietal cortex. Interestingly, even 1000 lux light failed to induce Per2 mRNA in the parietal cortex. These clock gene-specific and brain region-dependent responses to lights in the OB and parietal cortex suggest that single light stimulus induces various physiological functions in different brain areas via specific clock gene.

The Olfactory Bulb Provides a Radioresistant Niche for Glioblastoma Cells.

PURPOSE: The various microenvironments that exist within the brain combined with the invasive nature of glioblastoma (GBM) creates the potential for a topographic influence on tumor cell radiosensitivity. The aim of this study was to determine whether specific brain microenvironments differentially influence tumor cell radioresponse. METHODS AND MATERIALS: GBM stem-like cells were implanted into the right striatum of nude mice. To measure radiosensitivity, proliferation status of individual tumor cells was determined according to the incorporation of 5-chloro-2'-deoxyuridine delivered at 4, 12, and 20 days after brain irradiation. As an additional measure of radiosensitivity, the percentage of human cells in the right hemisphere and the olfactory bulb were defined using digital droplet polymerase chain reaction. Targeted gene expression profiling was accomplished using NanoString analysis. RESULTS: Tumor cells were detected throughout the striatum, corpus callosum, and olfactory bulb. After an initial loss of proliferating tumor cells in the corpus callosum and striatum after irradiation, there was only a minor recovery by 20 days. In contrast, the proliferation of tumor cells located in the olfactory bulb began to recover at 4 days and returned to unirradiated levels by day 12 postirradiation. The percentage of human cells in the right hemisphere and the olfactory bulb after irradiation also suggested that the tumor cells in the olfactory bulb were relatively radioresistant. Gene expression profiling identified consistent differences between tumor cells residing in the olfactory bulb and those in the right hemisphere. CONCLUSIONS: These results suggest that the olfactory bulb provides a radioresistant niche for GBM cells.

p53 Loss Mitigates Early Volume Deficits in the Brains of Irradiated Young Mice.

PURPOSE: Pediatric cranial radiation therapy results in lasting changes in brain structure. Though different facets of radiation response have been characterized, the relative contributions of each to altered development is unclear. We sought to determine the role of radiation-induced programmed cell death, as mediated by the Trp53 (p53) gene, on neuroanatomic development. METHODS AND MATERIALS: Mice having a conditional knockout of p53 (p53KO) or wildtype p53 (WT) were irradiated with a whole-brain dose of 7 Gy (IR; n = 30) or 0 Gy (sham; n = 28) at 16 days of age. In vivo magnetic resonance imaging was performed before irradiation and at 4 time points after irradiation, until 3 months posttreatment, followed by ex vivo magnetic resonance imaging and immunohistochemistry. The role of p53 in development was assessed at 6 weeks of age in another group of untreated mice (n = 37). RESULTS: Neuroanatomic development in p53KO mice was normal. After cranial irradiation, alterations in neuroanatomy were detectable in WT mice and emerged through 2 stages: an early volume loss within 1 week and decreased growth through development. In many structures, the early volume loss was partially mitigated by p53KO. However, p53KO had a neutral or negative impact on growth; thus, p53KO did not widely improve volume at endpoint. Partial volume recovery was observed in the dentate gyrus and olfactory bulbs of p53KO-IR mice, with corresponding increases in neurogenesis compared with WT-IR mice. CONCLUSIONS: Although p53 is known to play an important role in mediating radiation-induced apoptosis, this is the first study to look at the cumulative effect of p53KO through development after cranial irradiation across the entire brain. It is clear that apoptosis plays an important role in volume loss early after radiation therapy. This early preservation alone was insufficient to normalize brain development on the whole, but regions reliant on neurogenesis exhibited a significant benefit.

Olfactory bulb plasticity ensures proper olfaction after severe impairment in postnatal neurogenesis.

The olfactory bulb (OB) neurons establish a complex network that ensures the correct processing of the olfactory inputs. Moreover, the OB presents a lifelong addition of new neurons into its existing circuitry. This neurogenesis is considered essential for the OB function. However, its functional impact on physiology and behavior is still unclear. Here, we investigate the mechanisms of OB plasticity that underlie bulbar physiology in relation to severe damage of neurogenesis. The neurogenesis of young mice was altered by ionizing radiation. Afterwards, both multi-channel olfactometry and electrophysiological studies were performed. Furthermore, neurogenesis and differentiation of the newly formed cells were assessed using bromodeoxyuridine labeling combined with a wide battery of neuronal markers. Our results demonstrate a reduction in both neurogenesis and volume of the OB in irradiated animals. The number of neuroblasts reaching the OB was reduced and their differentiation rate into interneurons selectively changed; some populations were noticeably affected whereas others remained preserved. Surprisingly, both olfactory detection and discrimination as well as electrophysiology presented almost no alterations in irradiated mice. Our findings suggest that after damaging postnatal neurogenesis, the neurochemical fate of some interneurons changes within a new biological scenario, while maintaining homeostasis and olfaction.

Effect of whole-brain irradiation on the specific brain regions in a rat model: Metabolic and histopathological changes.

Effect of ionizing radiation on the brain affects neuronal, glial, and endothelial cell population and lead to significant morphological, metabolic, and functional deficits. In the present study we investigated a dose- and time-dependent correlation between radiation-induced metabolic and histopathological changes. Adult male Wistar rats received a total dose of 35Gy delivered in 7 fractions (dose 5Gy per fraction) once per week in the same weekday during 7 consecutive weeks. Proton magnetic resonance spectroscopy (1H MRS), histochemistry, immunohistochemistry and confocal microscopy were used to determine whether radiation-induced alteration of the brain metabolites correlates with appropriate histopathological changes of neurogenesis and glial cell response in 2 neurogenic regions: the hippocampal dentate gyrus (DG) and the subventricular zone-olfactory bulb axis (SVZ-OB axis). Evaluation of the brain metabolites 18-19 weeks after irradiation performed by 1H MRS revealed a significant decrease in the total N-acetylaspartate to total creatine (tNAA/tCr) ratio in the striatum and OB. A significant decline of gamma-aminobutyric acid to tCr (GABA/tCr) ratio was seen in the OB and hippocampus. MR revealed absence of gross inflammatory or necrotic lesions in these regions. Image analysis of the brain sections 18-21 weeks after the exposure showed a radiation-induced increase of neurodegeneration, inhibition of neurogenesis and strong resemblance to the reactive astrogliosis. Results showed that fractionated whole-brain irradiation led to the changes in neurotransmission and to the loss of neuronal viability in vivo. Metabolic changes were closely associated with histopathological findings, i.e. initiation of neuronal cell death, inhibition of neurogenesis and strong response of astrocytes indicated development of late radiation-induced changes.

Effects of repeated 9 and 30-day exposure to extremely low-frequency electromagnetic fields on social recognition behavior and estrogen receptors expression in olfactory bulb of Wistar female rats.

OBJECTIVE: We investigated the short- and long-term effects of extremely low-frequency electromagnetic fields (EMF) on social recognition behavior and expression of α- and ß-estrogen receptors (ER). METHODS: Rats were exposed to 60-Hz electromagnetic fields for 9 or 30 days and tested for social recognition behavior. Immunohistochemistry and western blot assays were performed to evaluate α- and ß-ER expression in the olfactory bulb of intact, ovariectomized (OVX), and ovariectomized+estradiol (E2) replacement (OVX+E2). RESULTS: Ovariectomization showed impairment of social recognition after 9 days of EMF exposure and a complete recovery after E2 replacement and so did those after 30 days. Short EMF exposure increased expression of ß-ER in intact, but not in the others. Longer exposure produced a decrease in intact but an increase in OVX and OVX+E2. DISCUSSION: Our findings suggest a significant role for ß-estrogen receptors and a lack of effect for α-estrogen receptors on a social recognition task. ABBREVIATIONS: EMF: extremely low frequency electromagnetic fields; ERs: estrogen receptors; OB: olfactory bulb; OVX: ovariectomized; OVX + E2: ovariectomized + estradiol replacement; IEI: interexposure interval; ß-ER: beta estrogen receptor; E2: replacement of estradiol; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; WB: Western blot; PBS: phosphate-buffer saline; PB: phosphate-buffer.

Early X-irradiation of rats--II. Effect on granule cells and their dendrodendritic synapses in the olfactory bulb.

Low, repeated doses of X-rays from a Co60 source were used to impair the development of the granule cells and their dendritic terminals in the olfactory bulb, and the resulting effect was studied under light and electron microscopes at 9 days of age. Irradiation of rats from embryonic day 18 (in utero) to postnatal day 5 resulted, among others, in maldevelopment of the (internal) granule cell and external plexiform layers. This was accompanied by a decrease in the number and the density of the granule cells, and the remaining granule cells contained less ribosomes, regardless of their position within the layer. This implies that both supposed subtypes of granule cells were effected. In the external plexiform layer, a reduced number of mature dendrodendritic synapses and signs of harmed granule gemmules were observed. The results suggest that intrauterinal plus postnatal irradiation with low, repeated doses of X-rays may be an effective tool impairing the development of prenatally forming neurons.

Establishment of modified chimeric mice using GFP bone marrow as a model for neurological disorders.

Chimeric mice stably reconstituted with bone marrow cells represent a good model for analysis of the mechanism of bone marrow cell infiltration in the brain. However, in preparing chimeric mice, irradiation of the recipient mice is necessary to kill their own bone marrow before transplantation, which induces gliosis and inflammatory response by activation of astrocytes and microglia in the brain. Here, we determined the most suitable dose of irradiation associated with the least brain damage before transplantation for reconstitution of chimeric mice, using FACS analysis. Our mouse model of 10 Gy body/5 Gy head irradiation should be useful for investigating the mechanism(s) of microglial activation in various neurological disorders such as stroke, Alzheimer's disease and Parkinson's disease.

Early X-irradiation of rats. 1. Methodological description and morphological observations on the olfactory bulb.

X-ray irradiation of rats in utero and during early postnatal days was performed using low, fragmented doses from a 60Co radiation source. Different radiation schedules were applied in order to impair the development of certain neurons. The effect of radiation on the main olfactory bulb was characterized in several ways. Early X-ray irradiation resulted in retardation of dams and young pups and an underdevelopment of the bulb and its main histological layers, especially the granule cell and external plexiform layers, but a disturbed glomerular development was also apparent. The resulting damage was proportional to the magnitude of the irradiation. The present technique seems to be useful in eliciting damage in separate populations of pre- or postnatally forming neurons.

Head-portion exposure to low-level X-rays reduces isolation-induced aggression of mouse, and involvement of the olfactory carnosine in modulation of the radiation effects.

Social isolation has been widely described to induce a compulsive aggressive behavior. The aggressiveness due to isolation in mice has often been used as a means for the better understanding of disturbed behavior in human beings. In the course of a study of the behavioral effects, we have noticed that fighting injuries, usually observed among male ICR mice, tend to decrease in mice irradiated with low-dose X-rays. We, therefore, quantitatively examined the effects of low-dose X-irradiation on aggressive behavior using a resident-intruder paradigm in which a resident mouse attacks an intruder that entered its territory. Male ICR white Swiss mice became gradually calm, and showed remarkably quiet behavior 7-10 days after whole-head 5 or 15 cGy X-irradiation. Only exposure of the anterior part of the head (olfactory system including orbits) also induced the remarkable suppression of the aggressive behavior. The olfactory system has direct access to the limbic system, a central part of the brain concerned with emotion. The calm behavior induced by low-dose X-irradiation might be related to the changes in the olfactory function. We also obtained data on brain biochemistry giving further support for the above low-dose effects on mouse behavior. The carnosine content and its synthetase activity in the olfactory bulbs decreased significantly after only the anterior part of the head had been exposed. Higher doses (25-35 cGy), however, did not induce such effects. The results suggest that the depression of aggressive behavior is limited to animals irradiated with the smaller doses.

Light microscope differentiation of two populations of rat olfactory bulb granule cells.

Examination of glycolmethacrylate embedded olfactory bulbs of normal rats revealed that the granule cells of the accessory olfactory bulb were dissimilar from the majority of main olfactory bulb granule cells. Cells from these structures can be discriminated on the basis of spherical form. nuclear diameter, nucleoplasm staining, basal dendritic arborizations, and susceptibility to loss after neonatal X-irradiation. Based on their staining qualities, we have called these cells light and dark granule cells. In the normal rat the dark granules make up about 85% of granule cells in the main olfactory bulb and is the cell type preferentially killed by neonatal X-irradiation. Timing of postnatal X-irradiation and consequent differential loss of the dark type of main olfactory bulb granule cell suggests that the light type is largely prenatally formed.

Quantitation of heavy ion damage to the mammalian brain: some preliminary findings.

Histological preparations of brains from rabbits and mice exposed to different doses of various HZE particles or to low-LET photons have been subjected to preliminary quantitation of radiation-induced morphometric changes. Computer assisted measurements of several brain structures and cell types have been made using the KONTRON Automated Interactive Measurement System (IBAS, Carl Zeiss, Inc., Thornwood, N.Y. 10594 U.S.A.). New Zealand white rabbits irradiated at approximately 6 weeks of age were euthanatized 6.5-25 months after exposure to 60Co gamma photons (LET infinity = approximately 0.3 keV/micrometer, 20Ne particles (LET infinity = 35 +/- 3 keV/micrometer), or 40Ar particles (LET infinity = 90 +/- 5 keV/micrometer). Measurements of stained sections of the olfactory bulbs of those animals indicate that the mean size (volume) of olfactory glomeruli is reduced in a dose-dependent (and perhaps an LET-dependent) manner as soon as 6.5 months after irradiation. Differences between mean volumes of additional structures have been noted when histological preparations of control mouse brains were compared with irradiated specimens. Quantitation of intermediate and late changes in nervous (and other) tissues exposed to low- and high-LET radiations will improve our ability to predict late effects in tissues of astronauts and others exposed to the radiation hazards of the space environment.

Morphometric studies of heavy ion damage in the brains of rodents.

As an approach to determining the relative biological effectiveness (RBE) of each of five different heavy ions for the mammalian brain, histological preparations of brains from mice exposed to various HZE particles at different doses and primary LETinfinity values were examined by means of semi-automated image analysis for volume changes in specific regions of the olfactory bulb. The mice were irradiated at 100 days of age and euthanatized about 500 days (16 months) later. Exposures were: 60Co gamma photons (LETinfinity = 1-2 keV/micrometer), 4He (LETinfinity = 6 keV/micrometer), 12C (LETinfinity = 80 keV/micrometer), 20Ne (LETinfinity = 150 keV/micrometer), 56Fe (LETinfinity = 180 keV/micrometer), and 40Ar (LETinfinity = 650 keV/micrometer). Animals receiving particle radiation were exposed in an extended Bragg peak region except for iron where the plateau region was used. The zones measured in the olfactory bulb were 1) the external plexiform layer (zone) and 2) an internal region consisting of the granule cells, internal plexiform layer, and layer of mitral cells. These studies indicated that volume changes did indeed occur, not only in absolute terms but also when expressed as the ratio of the structures to each other and to the bulb as a whole. Although this study is exploratory in character, the data obtained may nevertheless contribute to a determination of risk factors due to late effects from HZE articles.

Olfactory bulb volume and olfactory function after radiotherapy in patients with nasopharyngeal cancer.

OBJECTIVE: Radiotherapy is the primary method of treatment for nasopharyngeal cancer (NPC) and many side effects were reported in patients receiving radiation to this area. This study was conducted to evaluate the long-term effects of radiotherapy following NPC on olfactory bulb (OB) volume and olfactory function. METHODS: Twenty-four patients with NPC who received radiotherapy at least 12 months ago were recruited. Fourteen healthy subjects with similar demographical characteristics were recruited as the healthy control group. All volunteers were subjected to a nasoendoscopical examination, and abnormalities that could potentially cause olfactory dysfunction were the exclusion criteria from the study. An experienced radiologist segmented the MRI coronal, axial and sagittal slices manually for three-dimensional OB volume measurement in a blinded manner. Olfactory function was assessed using the Connecticut Chemosensory Clinical Research Center (CCCRC) test, and average score (0: worst, 7: best) was calculated as the total CCCRC olfactory score. RESULTS: The mean CCCRC score was 5.5 ± 1.1 for the nasopharyngeal cancer patients, whereas the mean score of healthy control group was 6.4 ± 0.4. There was a significant difference in the olfactory scores (p=0.003). The mean OB volume in the NPC group was 46.7 ± 12.1mm(3). Among the patients with NPC, the cisplatin receiving group had a mean OB volume of 47.2mm(3), whereas the cisplatin+docetaxel receiving group had a mean OB volume of 46.5mm(3), and they were similar. The MRI measurement of the healthy control group was 58.6 ± 13.8mm(3). The OB volumes of the healthy control group were significantly higher (p<0.05). CONCLUSION: Radiotherapy following nasopharyngeal cancer results in a diminished OB volume and deteriorated olfactory function. Chemosensory olfactory dysfunction might be a contributing factor to lack of appetite, cancer cachexia and consequent lowered quality of life in NPC patients.