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PubMed1990

Inhibitory effects of centrally and peripherally induced anosmia on mounting behavior in the female rat.

Adult ovariectomized female rats received a testosterone-propionate (TP)-filled silastic implant and were tested for mounting behavior seven days later. Exposure to estrous female urine but not to urine from ovariectomized females increased the number of TP-treated females that displayed mounting behavior. Olfactory bulb removal on its own and peripheral anosmia induced by intranasal ZnSO4 application impaired mounting behavior. These results are discussed with respect to the effects of anosmia on copulatory behavior in the male.

Animals↗
PubMed1988

Functional ablation of the olfactory bulb by spreading depression: unit activity changes and transient anosmia.

Cortical spreading depression (SD) is widely used to induce functional decortication. Development of a reliable technique for eliciting SD in the olfactory bulb (OB) of rats makes it possible to achieve functional elimination of the first relay of the olfactory pathway. In order to assess the unit activity changes accompanying OBSD, adult male hooded rats (n = 31) were anesthetized with pentobarbital and activity of OB units was recorded with carbon fiber microelectrodes. The predepression activity (12.7 +/- 0.8 Hz) increased up to 35.1 +/- 4.1 Hz during the burst which attained maximum 44 +/- 6 sec after K+ acetate injection and corresponded to the steep depolarization phase of SD slow potential. The burst lasted 20.4 +/- 2.9 sec on the average and was followed by 187 +/- 20 sec of complete silence. Gradual recovery to the predepression level lasted 229 +/- 27 sec. Activity of most units (63%) in the contralateral OB was not changed. Significant reactions of OB neurons to ipsilateral cortical SD found in 57% units were mostly inhibitory (49%). OBSD-induced anosmia was examined in a group of rats (n = 8) with unilateral bulbectomy and a guiding tube implanted into the remaining OB for microinjection of K+ acetate. One week after surgery, the animals were examined in the food-retrieval olfactory test. The microinjection of K+ acetate severely disrupted the food finding behavior in 60% rats during 3-min test. Both electrophysiological and behavioral results indicate that OBSD is a convenient tool for inducing short-lasting anosmia.

Action Potentials↗
PubMed1997

Olfactory event-related potentials to amyl acetate in congenital anosmia.

Olfactory function was evaluated by olfactory event-related potentials and standardized psychophysical measures including the Smell Identification Test and odor detection threshold tests for 3 chemosensory stimulants in 9 subjects with isolated congenital anosmia and 9 age- and gender-matched normosmic controls. There was a significant difference in Smell Identification Test scores (P < 0.001) and odor detection thresholds for phenylethyl alcohol (P < 0.001) and isoamyl acetate (P < 0.001) between the anosmic and normosmic subjects. Detection thresholds for chloracetyl phenone, a trigeminal stimulant, did not differ between the 2 groups. Olfactory evoked potentials were recorded in response to amyl acetate and air control stimuli presented at volume flow rate of 5 l/min, stimulus duration of 40 ms, and randomized interstimulus intervals of 6-30 s. In the control subjects, evoked potentials to amyl acetate were characterized by 4 reproducible components (P1, N1, P2, and N2). In the subjects with congenital anosmia, no reproducible evoked potential components were identified in response to amyl acetate. No reproducible evoked potential components were seen in response to the air control stimulus in either the anosmic or normosmic groups. These data suggest that olfactory evoked potentials provide a specific measure of olfactory function.

Adult↗
PubMed1986

Effect of anosmia on reproduction in male and female wolves (Canis lupus).

Anosmia was produced in two female and three male wolves by transection of the olfactory peduncle and was confirmed by their inability to detect meat, urine, feces, anal-gland secretions, and fish emulsion. All operated animals continued to investigate the environment with their noses, to interact normally with other pack members, and to feed at levels which maintained presurgical body weights. No effect was found on reproductive physiology (females: estradiol or progesterone concentrations, ovulation, pregnancy or parturition; males: testosterone, testicular recrudescence or sperm numbers, motility or maturation). One anosmic female became dominant and although she urine-marked with a flexed leg, the rate was lower than typical for dominant females and perhaps contributed to her failure to pair-bond with the dominant male. One anosmic male raised-leg-urinated while competing for pack dominance and when kenneled away from other males. Precopulatory, copulatory, and maternal behavior were observed for one anosmic female and appeared normal. However, neither male that was sexually naive before surgery showed interest in proestrous or estrous females. The possibility that secondary degeneration of brain regions mediating sexual behavior was responsible for the failure of these males to respond was not supported. Not only was the lack of male sexual response the only serious deficit following transection, but the male which was sexually experienced prior to surgery did copulate successfully during his second postoperative breeding season despite continued anosmia. Chemosensory priming from female urine during the protracted proestrous phase, as well as urinary and vaginal odors during estrus, appear to be critical for induction of full sexual potency in sexually naive males. The importance of urine and vaginal secretions in the sexual response of experienced males is uncertain.

Animals↗
PubMed2001

Persistent c-fos expression and NADPH-d reactivity in the medulla and the lumbar spinal cord in rat with short-term peripheral anosmia.

Here we examine hypothesis that short-term peripheral ZnSO(4)-induced anosmia can produce effects on c-fos expression within spinal cord and caudal medulla in male Wistar rats (n=4). Fos-like-immunoreactive cells revealed by avidin-biotin-peroxidase method show a significant bilateral increase in the nucleus proprius (layers 3 and 4) and medial part of layers 5 and 6. In substantia gelatinosa (layer 2(i)) and area 10 Fos-positive neurons were intermixed together with nicotin-amide adenine dineucleotide phosphate-diaphorase (NADPH-d)-reactive cells. Short-term anosmia enhanced c-fos expression in ventral horn (layers 7 and 8), ventrolateral segment and dorsal part of the spinal trigeminal nuclei. In anosmic rats varicose fibres and numerous NADPH-d-stained neurons were present in the gelatinous layer of the spinal trigeminal nucleus caudalis, and a separate population of Fos-positive cells was detected within this layer. Nucleus tractus solitaris also contained a few NADPH-d-reactive, medium sized neurons intermixed with Fos-immunoreactive cells.

Animals↗
PubMed2001

Maternal selectivity suppression through peripheral anosmia affects neither overall nursing frequency and duration, nor lactation performance in ewes.

The effects of prepartum peripheral anosmia on nursing activity, milk production and growth of the lambs, were assessed by comparing intact (n=10) and anosmic (n=10) multiparous Columbia and Rambouillet ewes and their single lamb during the first 2 months of lactation. Intact mothers only nursed their own lamb (98%) while most of the nursing activity in anosmic mothers concerned alien lambs (78%). On the other hand, the total duration and the frequencies of nursing did not differ significantly between groups (P>0.05). Nevertheless, the total percentage of nursing of own lamb by anosmic mothers (22%) was higher than expected at random (10%). Milk production or lambs' weights did not differ between groups. We conclude that prepartum anosmia resulted in the failure of ewes to develop true selective nursing up to the 8th week of lactation, although some preferential mother-young relationship yet developed. On the other hand, it did not affect significantly overall nursing activity.

Journal Article↗
PubMed2001

Zinc sulphate-induced anosmia decreases the nerve fibre density in the anterior cerebral artery of the rat.

Detailed quantitative studies have demonstrated a topographical heterogeneity of nerve fibre densities in the cerebral arteries at the base of the brain as well as local changes in ageing and Alzheimer's patients. In this study, we test the hypothesis that local patterns of innervation are influenced by changes in flow fluctuations. This was investigated by inducing chronic anosmia and monitoring the nerve fibre density in the basal cerebral arteries in the adult rat. The olfactory epithelium was examined after staining with hematoxylin and eosin and showed a marked reduction of thickness in the anosmic group compared to the control group. The olfactory bulb was histochemically stained for succinate dehydrogenase (SDH) activity and showed a reduced staining in the anosmic group compared to the controls. Whole mount preparations of the basal cerebral arteries were immunostained for the general neural marker protein gene product (PGP) 9.5. The nerve fibre densities of the vessel walls were quantified by image analysis and expressed as area percentage and intercept density. This analysis showed a significant reduction in area percentage for the first part of the anterior cerebral artery, as well as for the second part of the anterior cerebral artery, and a significant reduction in intercept density for the second part of the anterior cerebral artery in the anosmic group. We conclude that peripherally induced anosmia decreases nerve fibre density in the anterior cerebral artery that may be due to a decreased metabolic activity in the rhinencephalon and, as a consequence, a reduction of flow fluctuations in the blood vessels supplying this area occurs.

Animals↗
PubMed2004

Loss of BBS proteins causes anosmia in humans and defects in olfactory cilia structure and function in the mouse.

Defects in cilia are associated with several human disorders, including Kartagener syndrome, polycystic kidney disease, nephronophthisis and hydrocephalus. We proposed that the pleiotropic phenotype of Bardet-Biedl syndrome (BBS), which encompasses retinal degeneration, truncal obesity, renal and limb malformations and developmental delay, is due to dysfunction of basal bodies and cilia. Here we show that individuals with BBS have partial or complete anosmia. To test whether this phenotype is caused by ciliary defects of olfactory sensory neurons, we examined mice with deletions of Bbs1 or Bbs4. Loss of function of either BBS protein affected the olfactory, but not the respiratory, epithelium, causing severe reduction of the ciliated border, disorganization of the dendritic microtubule network and trapping of olfactory ciliary proteins in dendrites and cell bodies. Our data indicate that BBS proteins have a role in the microtubule organization of mammalian ciliated cells and that anosmia might be a useful determinant of other pleiotropic disorders with a suspected ciliary involvement.

Animals↗
PubMed2002

Brief report: anosmia and remote outcome in closed head injury.

The value of posttraumatic anosmia as a predictor of late social outcomes was examined in a sample of closed head injury (CHI) patients. Unemployment rates were equally high in both the anosmic and nonanosmic closed head injury patients. The groups also did not differ in psychiatric or neuropsychological status. Anosmic patients had longer initial hospital stays and deeper initial comatose/confusional states. Anosmia does not appear to add incrementally to disability status and it does not automatically imply the presence of basal-frontal damage.

Cognition↗
PubMed1988

Prognostic significance of anosmia in patients with closed-head trauma.

Among 40 patients who developed total anosmia as a result of closed-head injury, virtually all had major vocational problems during the two or more years after being medically cleared to return to work. None had major motor or sensory deficits, and the majority had above average intelligence and memory. However, most demonstrated psychosocial deficits of a type typically associated with damage to orbital frontal cortex. Vocational outcome for patients with partial anosmia was more variable with only about half having manifest vocational problems.

Adult↗
PubMed1999

Assessing the impact of anosmia: review of a questionnaire's findings.

The inability to detect odours, anosmia, can cause profound psychological effects resulting in feelings of physical and social vulnerability and victimization. In addition, there may be unhappiness related to the loss of the ability to detect pleasurable food smells and, as a consequence, anosmics may develop problems relating to eating. These profound effects arise from a condition which can have a rapid onset and a very poor prognosis for recovery, and are largely treated with a lack of sympathy and indifference by people with normal olfactory ability. In an attempt to educate, inform and help sufferers, a questionnaire was developed in the early 1980s and sent to those who contacted the Warwick Olfaction Research Group. The responses from this questionnaire form the basis of this review. Feelings of personal isolation, lack of interest in eating and emotional blunting were common responses from these sufferers and it seems that we still have some way to go before an adequate recognition of problems associated with anosmia is gained by the general population and, more importantly, within the medical profession.

Feeding Behavior↗
PubMed2006

Mutations in olfactory signal transduction genes are not a major cause of human congenital general anosmia.

Anosmia affects the western world population, mostly the elderly, reaching to 5% in subjects over the age of 45 years and strongly lowering their quality of life. A smaller minority (about 0.01%) is born without a sense of smell, afflicted with congenital general anosmia (CGA). No causative genes for human CGA have been identified yet, except for some syndromic cases such as Kallman syndrome. In mice, however, deletion of any of the 3 main olfactory transduction components (guanidine triphosphate binding protein, adenylyl cyclase, and the cyclic adenosine monophosphate-gated channel) causes profound reduction of physiological responses to odorants. In an attempt to identify human CGA-related mutations, we performed whole-genome linkage analysis in affected families, but no significant linkage signals were observed, probably due to the small size of families analyzed. We further carried out direct mutation screening in the 3 main olfactory transduction genes in 64 unrelated anosmic individuals. No potentially causative mutations were identified, indicating that transduction gene variations underlie human CGA rarely and that mutations in other genes have to be identified. The screened genes were found to be under purifying selection, suggesting that they play a crucial functional role not only in olfaction but also potentially in additional pathways.

Chromatography, High Pressure Liquid↗
PubMed1999

Neuropsychological significance of anosmia following traumatic brain injury.

OBJECTIVES: To investigate the incidence of anosmia following traumatic brain injury (TBI) using a standardized instrument and to test hypotheses that post-TBI anosmics perform significantly more poorly than do post-TBI normosmics on measures of executive skills and functional outcome. DESIGN: Prospective quasi-experimental between-groups design. PARTICIPANTS: Sixty-eight adults diagnosed with TBI. SETTING: Brain injury rehabilitation program based at a Midwestern medical center. MAIN OUTCOME MEASURES: University of Pennsylvania Smell Identification Test (UPSIT), selected neuropsychological measures of executive skills, the Disability Rating Scale (DRS), and the Community Integration Questionnaire (CIQ). RESULTS: Forty-four subjects (65%) demonstrated impaired olfaction; only 13 (30%) acknowledged smell dysfunction. Anosmic and normosmic groups did not differ in demographics, IQ, chronicity, or admission Glasgow Coma Scale (GCS). Anosmics had longer coma (P =. 01), more severe deficits in complex attention (Trailmaking Test, Part B, P =.01), new learning/memory (California Verbal Learning Test Trial V [CVLT-V], P =.001), and problem solving (Wisconsin Card Sorting Test [WCST], P =.001), leading to greater functional impairment (Disability Rating Scale [DRS], P =.003). No differences emerged on the CIQ. CONCLUSIONS: Anosmia is a common sequela of TBI, although only a minority of patients are aware of this deficit. Further, anosmics demonstrated greater impairment in a variety of frontal-lobe mediated executive functions, as well as greater functional disability.

Adult↗
PubMed1996

Anosmia after anterior communicating artery aneurysm surgery: comparison between the anterior interhemispheric and basal interhemispheric approaches.

The olfactory function could be examined in 101 of 138 patients with anterior communicating artery aneurysms, whom we treated during a recent 6-year period. Among them, 49 patients underwent surgery by the anterior interhemispheric approach and 52 underwent surgery by the basal interhemispheric approach. Fifteen patients (31%) exhibited anosmia after surgery by the anterior interhemispheric approach, whereas only one patient (1.9%) exhibited anosmia after surgery by the basal interhemispheric approach. Unilateral dural incision and unilateral brain retraction without elevation of the frontal lobe from the frontal base are important, because frontal lobe depression and elevation during surgery may injure the olfactory nerve.

Adult↗
PubMed1981

The effect of anosmia on smoking habits.

Sixteen cigarette smokers who had developed complete anosmia were questioned about their smoking habits. Four subjects increased their cigarette consumption, 8 were unchanged and 4 decreased. The development of anosmia has no consistent effect on cigarette smoking.

Adult↗
PubMed1975

Effects of pinealectomy, anosmia and blinding on serum and pituitary prolactin in intact and castrated male rats.

Serum prolactin was measured in lightly etherized rats between 4 and 5 a.m. and between 11 a.m. and 12 noon at various times after operation in intact rats and rats that had been operated on. Serum prolactin was elevated in the late nocturnal samples from intact rats and this elevation was prevented by pinealectomy. With time following the operation, daytime serum prolactin was also lowered in pinealectomized animals. In animals rendered anosmic by olfactory bulb removal, serum prolactin was also lowered. Superimposed pinealectomy only lowered late nocturnal serum prolactin in anosmic rats. Blinding the rats by ocular enucleation lowered nocturnal serum prolactin initially and dampened the daily rhythm in prolactin, but superimposed pinealectomy had no effect on the blinded animals. The combined sensory deprivation produced by both blinding and olfactory bulb removal resulted in low prolactin titers regardless of whether blood samples were taken during the day or late at night and, as in the case of blinded animals, there was no effect of pinealectomy. Superior cervical ganglionectomy also lowered serum prolactin. Serum prolactin declined following castration in intact animals and this decline was accentuated by pinealectomy. Either blinding or anosmia also lowered serum prolactin in the castrated animals but, as in intact animals, pinealectomy had little effect on the sensory-deprived rats. A further lowering of prolactin occurred in castrated animals which were both blinded and anosmic; in these animals, pinealectomy again had no additional effect. Measurement of the pituitary prolactin content in the castrated animals at sacrifice revealed a significant lowering of values in blinded animals, with restoration of the values to control levels by pinealectomy. Anosmia also lowered the pituitary prolactin content but this was not reversed by pinealectomy. The lowest pituitary prolactin was found in blinded, anosmic animals and these changes were not reversed by pinealectomy. The weight of the pineal gland increased significantly in anosmic, blinded, or blinded and anosmic rats. It is concluded that pineal secretions in the male rat elevate serum prolactin, particularly late at night, and that loss of input from olfactory and to a lesser extent from visual pathways results in a decrease in the titer of the hormone. This decrease is especially apparent in blinded, anosmic rats.

Animals↗
PubMed1986

Incidence of specific anosmia in Northern Germany.

Thresholds for the perception of 6 primary odorants were tested in a sample of 153 unrelated healthy individuals including 101 males and 52 females. Using some special precautions and directions for preparing aqueous solutions of primary odorants, screening for specific anosmia was found to be a practicable method with reliable results. The observed perception thresholds showed a bimodal distribution. Individuals with higher values probably are specific anosmics. Relatively lower frequencies of anosmia observed in this sample, as compared to reported values in Caucasians of the USA, are probably due to genetic differences. The pheromone character of some odorants and their possible genetic relevance is discussed.

Adolescent↗
PubMed2006

Novel fibroblast growth factor receptor 1 mutations in patients with congenital hypogonadotropic hypogonadism with and without anosmia.

CONTEXT: Kallmann syndrome is a clinically and genetically heterogeneous disorder. To date, loss-of-function mutations in the genes encoding anosmin-1 (KAL1) and fibroblast growth factor receptor 1 (FGFR1) have been described in the X-linked and autosomal dominant forms of this syndrome, respectively. OBJECTIVE: The objective was to investigate genetic defects in the KAL1 and FGFR1 genes in patients with congenital isolated hypogonadotropic hypogonadism (IHH). PATIENTS: Eighty patients (71 males and nine females) with IHH were studied, of which 30 were familial. Forty-six of them had olfactory abnormalities. METHODS: The coding regions of both KAL1 and FGFR1 genes were amplified and automatically sequenced. The KAL1 mutations were investigated only in patients with olfactory abnormalities, whereas FGFR1 was studied in the entire group. RESULTS: Two novel KAL1 mutations, an intragenic deletion of exons 3-6 and a splicing mutation IVS7 + 1G>A, were identified in two of 46 patients with Kallmann syndrome. Eight novel heterozygous FGFR1 mutations (G48S, L245P, R250W, A343V, P366L, K618fsX654, P722S, and V795I) were identified in nine of 80 patients with IHH. Eight of them had olfactory abnormalities. Interestingly, the G48S mutation was identified in a normosmic IHH patient. Two unrelated females, who carried FGFR1 mutations, had anosmia and normal reproductive function. CONCLUSION: We identified novel mutations in KAL1 and FGFR1 genes in IHH patients. FGFR1 mutations were identified in 17% of the patients with olfactory abnormalities and in one of 34 normosmic IHH patients. In addition, isolated anosmia was identified in two unrelated females as a partial phenotypic manifestation of FGFR1 defects.

Adolescent↗