Specific anosmia in humans and animals: Environmental and genetic influences

Abstract

M.A. Klyuchnikova, V.V. Voznessenskaya

Olfaction plays a very important role across the lifespan of most mammalian species, including humans. Being the oldest, chemical communication is one of the least understood forms of communication due in part to the difficulty of detecting and measuring the chemicals in a sample. The ability to detect chemicals in the environment serves many functions. Individuals with specific anosmia, or “odor blindness”, have significantly increased olfactory thresholds to particular odorants though they show normal general olfactory acuity. Hereby we review research on specific anosmia in humans, factors that may affect individual variation in olfaction as well as animal models of specific anosmia. Variability in sensitivity to odorants is influenced by genotype, age, gender, individual olfactory experience and environmental cues. Large data pile from human and animal studies suggests that not all factors are determined yet. The possibility of induction of olfactory sensitivity to biologically relevant chemical cues is discussed. Olfactory plasticity determines the adaptability of the species to the environment. Mechanisms that underlie the induction of sensitivity to the odorants still to be elucidated.
Keywords: Specific anosmia; chemical communication; olfactory receptors; environmental factors; androstenone; isovaleric acid
References
Abaffy, T., Matsunami, H., & Luetje, C. W. (2006). Functional analysis of a mammalian odorant receptor subfamily. J Neurochem, 97(5), 1506-1518. doi:10.1111/j.1471-4159.2006.03859.x
Amoore, J. E. (1952). The stereochemical specificities of human olfactory receptors. Perfum Essent Oil Rec., 33, 321-323.
Amoore, J. E. (1967). Specific anosmia: a clue to the olfactory code. Nature, 214(5093), 1095-1098. doi:10.1038/2141095a0
Amoore, J. E., Pelosi, P., & Forrester, L. J. (1977). Specific anosmias to 5α-androst-16-en-3-one and ω-pentadecalactone: the urinous and musky primary odors. Chemical Senses and Flavor, 2(4), 401-425. doi:10.1093/chemse/2.4.401.
Amoore, J. E. (1979). Directions for preparing aqueous solutions of primary odorants to diagnose eight types of specific anosmia. Chem Senses and Flavor, 4, 153-161. doi:10.1093/chemse/4.2.153.
Boesveldt, S., Postma, E. M., Boak, D., Welge-Luessen, A., Schopf, V., Mainland, J. D., Duffy, V. B. (2017). Anosmia-A Clinical Review. Chem Senses, 42(7), 513-523. doi:10.1093/chemse/bjx025.
Boryakova, E. E., Gladysheva, O. S., Krylov, V. N. (2007). Age dynamics of laboratory mice and rats females olfactory sensitivity to isovaleric acid. Sensornye sistemy, 21(4), 341-346. (in Russian)
Boyle, J. A., Lundstrom, J. N., Knecht, M., Jones-Gotman, M., Schaal, B., & Hummel, T. (2006). On the trigeminal percept of androstenone and its implications on the rate of specific anosmia. J Neurobiol, 66(13), 1501-1510. doi:10.1002/neu.20294
Bremner, E. A., Mainland, J. D., Khan, R. M., & Sobel, N. (2003). The prevalence of androstenone anosmia. Chem Senses, 28(5), 423-432. doi:10.1093/chemse/28.5.423
Buck, L., & Axel, R. (1991). A novel multigene family may encode odorant receptors: a molecular basis for odor recognition. Cell, 65(1), 175-187. doi:10.1016/0962-8924(91)90063-f
Bushdid, C., Magnasco, M. O., Vosshall, L. B., & Keller, A. (2014). Humans can discriminate more than 1 trillion olfactory stimuli. Science, 343(6177), 1370-1372. doi:10.1126/science.1249168
Chopra, A., Baur, A., & Hummel, T. (2008). Thresholds and chemosensory event-related potentials to malodors before, during, and after puberty: differences related to sex and age. Neuroimage, 40(3), 1257-1263. doi:10.1016/j.neuroimage.2008.01.015
Chukhrai, E.S., Atyaksheva, L. F., Poltorak, O. M., Voznesenskaya, V. V., Wysocki, C. J. (1997a). Modeling of the primary reception of odorants on natural transport proteins. Zhurnal Fizicheskoi Khimii, 71(2), 347-350.
Chukhrai, E. S., Poltorak, O. M., Atyaksheva, L. F., Veselova, M.N., Voznessenskaya, V. V., Wysocki, C. J. (1995). Soluable alkaline phosphatase as the transport protein of hydrophobic odorants. Zhurnal Fizicheskoi Khimii, 69(2), 336-339
Chukhrai, E. S., Poltorak, O. M., Atyaksheva, L. F., Voznessenskaya, V. V., Wysocki, C. J. (1997b). The influence of androstenone on the properties of immobilized alkali phosphatase in natural membranes responsible for reception of odorants. Zhurnal Fizicheskoi Khimii, 71(7), 1315-1319.
Chukhray, E. S., Veselova, M.N., Poltorak, O. M., Voznessenskaya, V. V., Zinkevich, E.P., Wysocki, C. J. (1992b). Phosphatase activity of rat olfactory and vomeronasal epithelial tissue. In Schulte, R. L., Doty, D., Muller-Schwarze (Eds.). Chemical Signals in Vertebrates 6 (pp. 43-47). Plenum Press. doi: 10.1007/978-1-4757-9655-1_8
Cowley, J. J., Johnson, A. L., & Brooksbank, B. W. (1977). The effect of two odorous compounds on performance in an assessment-of-people test. Psychoneuroendocrinology, 2(2), 159-172. doi:10.1016/0306-4530(77)90021-x
Croy, I., Olgun, S., Mueller, L., Schmidt, A., Muench, M., Hummel, C., Hummel, T. (2015). Peripheral adaptive filtering in human olfaction? Three studies on prevalence and effects of olfactory training in specific anosmia in more than 1600 participants. Cortex, 73, 180-187. doi:10.1016/j.cortex.2015.08.018
Dalton, P., Doolittle, N., & Breslin, P. A. (2002). Gender-specific induction of enhanced sensitivity to odors. Nat Neurosci, 5(3), 199-200. doi:10.1038/nn803
Dorries, K. M., Schmidt, H. J., Beauchamp, G. K., & Wysocki, C. J. (1989). Changes in sensitivity to the odor of androstenone during adolescence. Dev Psychobiol, 22(5), 423-435. doi:10.1002/dev.420220502
Doty, R. L., & Kamath, V. (2014). The influences of age on olfaction: a review. Applied Olfactory Cognition, 5, 213-232. doi:10.3389/fpsyg.2014.00020
Ferdenzi, C., Razafindrazaka, H., Baldovini, N., Poupon, D., Pierron, D., & Bensafi, M. (2019). Influence of gender and culture on the perception of acidic compounds of human body odor. Physiol Behav, 112561. doi: 10.1016/j.physbeh.2019.112561
Filsinger, E. E., Braun, J. J., Monte, W. C., & Linder, D. E. (1984). Human (Homo sapiens) responses to the pig (Sus scrofa) sex pheromone 5 alpha-androst-16-en-3-one. J Comp Psychol, 98(2), 219-222. doi:10.1037/0735-7036.98.2.219
Firestein, S., Picco, C., & Menini, A. (1993). The relation between stimulus and response in olfactory receptor cells of the tiger salamander. J Physiol, 468, 1-10. doi:10.1113/jphysiol.1993.sp019756
Gerkin, R. C., & Castro, J. B. (2015). The number of olfactory stimuli that humans can discriminate is still unknown. Elife, 4, e08127. doi:10.7554/eLife.08127
Gilbert, A. N., Wysocki C. J. (1987). The smell survey results. National Geographic, 172, 514-522.
Glusman, G., Yanai, I., Rubin, I., & Lancet, D. (2001). The complete human olfactory subgenome. Genome Res, 11(5), 685-702. doi:10.1101/gr.171001
Gower, D. B., & Ruparelia, B. A. (1993). Olfaction in humans with special reference to odorous 16-androstenes: their occurrence, perception and possible social, psychological and sexual impact. J Endocrinol, 137(2), 167-187. doi:10.1677/joe.0.1370167
Griff, I. C., & Reed, R. R. (1995). The genetic basis for specific anosmia to isovaleric acid in the mouse. Cell, 83(3), 407-414. doi:10.1016/0092-8674(95)90118-3
Guillot, M. (1948). Anosmies partielles et odeurs fondamentales. CR Hebd Acad Sci, 226, 1307–1309.
Hoehn, R. D., Nichols, D. E., Neven, H., & Kais, S. (2018). Status of the Vibrational Theory of Olfaction. Frontiers in Physics, 6(25). doi:10.3389/fphy.2018.00025
Hornung, J., Noack, H., Thomas, M., Farger, G., Nieratschker, V., Freiherr, J., & Derntl, B. (2018). Bayesian informed evidence against modulation of androstadienone-effects by genotypic receptor variants and participant sex: A study assessing Stroop interference control, mood and olfaction. Horm Behav, 98, 45-54.doi:10.1016/j.yhbeh.2017.12.003.
Hummel, T., Krone, F., Lundstrom, J. N., & Bartsch, O. (2005). Androstadienone odor thresholds in adolescents. Horm Behav, 47(3), 306-310. doi:10.1016/j.yhbeh.2004.10.007
Ingersoll, D. W., & Launay, J. (1986). Murine aggression induced by a boar chemosignal: a stimulus presentation dependency. Physiol Behav, 36(2), 263-269. doi:10.1016/0031-9384(86)90014-4
Kajiya, K., Inaki, K., Tanaka, M., Haga, T., Kataoka, H., & Touhara, K. (2001). Molecular bases of odor discrimination: Reconstitution of olfactory receptors that recognize overlapping sets of odorants. J Neurosci, 21(16), 6018-6025. doi:10.1523/jneurosci.21-16-06018.2001
Katada, S., Hirokawa, T., Oka, Y., Suwa, M., & Touhara, K. (2005). Structural basis for a broad but selective ligand spectrum of a mouse olfactory receptor: mapping the odorant-binding site. J Neurosci, 25(7), 1806-1815. doi:10.1523/jneurosci.4723-04.2005
Keller, A., & Vosshall, L. B. (2016). Olfactory perception of chemically diverse molecules. BMC Neurosci, 17(1), 55. doi:10.1186/s12868-016-0287-2
Keller, A., Zhuang, H., Chi, Q., Vosshall, L. B., & Matsunami, H. (2007). Genetic variation in a human odorant receptor alters odour perception. Nature, 449(7161), 468-472. doi.org/10.1038/nature06162
Klyuchnikova, M. A., Bosak, N. P., Lin, C., Bachmanov, A. A., Wysocki, C. J., Voznessenskaya, V. V. (2015). Genetic control of specific anosmia to androstenone in a mouse model. Chem Sens. 40(3), 277-278.
Klyuchnikova, M. A., Voznesenskaya, V. V. (2011). Genetic regulation of intermale aggression in the house mouse. Doklady Biol Sci. 436, 26-28. doi:10.1134/s0012496611010029
Knaapila, A., Tuorila, H., Silventoinen, K., Wright, M. J., Kyvik, K. O., Cherkas, L. F., Perola, M. (2008). Genetic and Environmental Contributions to Perceived Intensity and Pleasantness of Androstenone Odor: An International Twin Study. Chemosensory Perception, 1(1), 34-42. doi:10.1007/s12078-007-9005-x
Knaapila, A., Zhu, G., Medland, S. E., Wysocki, C. J., Montgomery, G. W., Martin, N. G., Reed, D. R. (2012). A genome-wide study on the perception of the odorants androstenone and galaxolide. Chem Senses, 37(6), 541-552. doi:10.1093/chemse/bjs008
Krautwurst, D., Yau, K. W., & Reed, R. R. (1998). Identification of ligands for olfactory receptors by functional expression of a receptor library. Cell, 95(7), 917-926. doi:10.1016/s0092-8674(00)81716-x
Labows, J., & Wysocki, C. (1984). Individual differences in odor perception. Perfumer & flavorist 9(1), 21-26.
Lapid, H., Seo, H. S., Schuster, B., Schneidman, E., Roth, Y., Harel, D., Hummel, T. (2009). Odorant concentration dependence in electroolfactograms recorded from the human olfactory epithelium. J Neurophysiol, 102(4), 2121-2130. doi:10.1152/jn.91321.2008
Liberles, S. D., & Buck, L. B. (2006). A second class of chemosensory receptors in the olfactory epithelium. Nature, 442(7103), 645-650. doi:10.1038/nature05066
Liberles, S. D. (2015). Trace amine-associated receptors: ligands, neural circuits, and behaviors. Current opinion in neurobiology, 34, 1-7. doi:10.1016/j.conb.2015.01.001
Lubke, K. T., & Pause, B. M. (2014). Sex-hormone dependent perception of androstenone suggests its involvement in communicating competition and aggression. Physiol Behav, 123, 136-141. doi: 10.1016/j.physbeh.2013.10.016.
Lunde, K., Egelandsdal, B., Skuterud, E., Mainland, J. D., Lea, T., Hersleth, M., & Matsunami, H. (2012). Genetic variation of an odorant receptor OR7D4 and sensory perception of cooked meat containing androstenone. PLoS ONE, 7(5), e35259. doi:10.1371/journal.pone.0035259.
Mainland, J. D., Bremner, E. A., Young, N., Johnson, B. N., Khan, R. M., Bensafi, M., & Sobel, N. (2002). Olfactory plasticity: one nostril knows what the other learns. Nature, 419(6909), 802. doi:10.1038/419802a
Malnic, B., Hirono, J., Sato, T., & Buck, L. B. (1999). Combinatorial receptor codes for odors. Cell, 96(5), 713-723. doi:10.1016/s0092-8674(00)80581-4
McGann, J. P. (2017). Poor human olfaction is a 19th-century myth. Science, 356(6338). doi:10.1126/science.aam7263
Melnik, S. A., Gladysheva, O. S., Krylov, V. N. (2009). Age-variation of olfactory sensitivity to isovaleric acid in male mice. Sensornye systemi. 23(2), 151-155. (in Russian)
Menashe, I., Abaffy, T., Hasin, Y., Goshen, S., Yahalom, V., Luetje, C. W., & Lancet, D. (2007). Genetic elucidation of human hyperosmia to isovaleric acid. PLoS Biol, 5(11), e284. doi:10.1371/journal.pbio.0050284
Menashe, I., Man, O., Lancet, D., & Gilad, Y. (2003). Different noses for different people. Nat Genet, 34(2), 143-144. doi:10.1038/ng1160
Michael, R. P., Bonsall, R. W., & Kutner, M. (1975). Volatile fatty acids, "copulins", in human vaginal secretions. Psychoneuroendocrinology, 1(2), 153-163. doi:10.1016/0306-4530(75)90007-4
Michael, R. P., Keverne, E. B., & Bonsall, R. W. (1971). Pheromones: isolation of male sex attractants from a female primate. Science, 172(986), 964-966. doi:10.1126/science.172.3986.964
Mombaerts, P. (2004). Odorant receptor gene choice in olfactory sensory neurons: the one receptor-one neuron hypothesis revisited. Curr Opin Neurobiol, 14(1), 31-36. doi:10.1016/j.conb.2004.01.014
Moncrieff, R. W. (1949). What is odor? A new theory. Am. Perfum. Essent. Oil Rev., 54, 453-454.
Muller-Schwarze, D., Muller-Schwarze, C., Singer, A. G., & Silverstein, R. M. (1974). Mammalian pheromone: Identification of active component in the subauricular scent of the male pronghorn. Science, 183, 860-862. doi:10.1126/science.183.4127.860
Novikov, S. N. (1988). Pheromones and reproduction in mammals: physiological aspects. Leningrad: Nauka. (in Russian)
Novikov, S. N., Troitskaya, V. T., Gladysheva, O. S., & Churakov, G. A. (2002). Specific anosmia to isovaleric acid in laboratory C57BL/6 mice: recessive inheritance. Dokl Biol Sci, 387, 505-507. doi.org/10.1023/a:1021768919888
Pause, B. M. (2004). Are androgen steroids acting as pheromones in humans? Physiol Behav, 83(1), 21-29. doi:10.1016/j.physbeh.2004.07.019
Poltorak, O. M., Chukhrai, E. S., Atyaksheva, L. F., Veselova, M. N., Voznessenskaya, V. V. (1997). Properties of immobilized alkaline phosphatase in native membranes at reception of odorants. Zhurnal Fizicheskoi Khimii, 71(8), 1505-1509.
Pourtier, L., & Sicard, G. (1990). Comparison of the sensitivity of C57BL/6J and AKR/J mice to airborne molecules of isovaleric acid and amyl acetate. Behav Genet, 20(4), 499-509. doi:10.1007/bf01067716
Price, S. (1977). Specific anosmia to geraniol in mice. Neurosci Lett, 4(1), 49-50. doi:10.1016/0304-3940(77)90123-9
Reed, H. C., Melrose, D. R., & Patterson, R. L. (1974). Androgen steroids as an aid to the detection of oestrus in pig artificial insemination. Br Vet J, 130(1), 61-67. doi:10.1016/s0007-1935(17)37337-2
Sato, T., Hirono, J., Tonoike, M., & Takebayashi, M. (1994). Tuning specificities to aliphatic odorants in mouse olfactory receptor neurons and their local distribution. J Neurophysiol, 72(6), 2980-2989. doi:10.1152/jn.1994.72.6.2980
Schmidt, H. J., & Beauchamp, G. K. (1988). Adult-like odor preferences and aversions in three-year-old children. Child Dev, (59), 1136-1143. doi:10.2307/1130280
Sicard, G., & Holley, A. (1984). Receptor cell responses to odorants: similarities and differences among odorants. Brain Res, 292(2), 283-296. doi:10.1016/0006-8993(84)90764-9
Sokolov, V. E., Voznesenskaia, V. V., Parfenova, V. M., & Wysocki, C. J. (1996). Induced sensitivity to odorants: a new phenomenon. Dokl Akad Nauk, 347(6), 843-846. (in Russian)
Sokolov, V. E., Voznessenskaya, V. V. (1997). A role of early olfactory experience in the individual recognition in gray rats (Rattus norvegicus). Dokl Akad Nauk, 355(1), 140-142. (in Russian)
Touhara, K. (2002). Odor discrimination by G protein-coupled olfactory receptors. Microsc Res Tech, 58(3), 135-141. doi:10.1002/jemt.10131
Touhara, K. (2008). Structure, expression, function of olfactory receptors. In Firestein, S. & Beauchamp G. K. (Eds.). The senses: A comprehensive reference. V.4. Olfaction and taste (pp. 527-544). Amsterdam, Boston: Elsevier. doi:10.1016/b978-012370880-9.00108-0
Troitskaia, V. T., Gladysheva, O. S., Novikov, S. N. (1987). Specific anosmia to isovaleric acid in the peripheral portion of the olfactory analyzer of the laboratory mouse. Neirofiziologiia, 19(1), 133-135. (in Russian)
Voznessenskaya, V. V., Parfyonova, V. M., Wysocki, C. J. (1995). Induced olfactory sensitivity in rodents: A general phenomenon. Adv Biosci, 93, 399-406.
Voznessenskaya, V. V., Wysocki, C. J., Chukhrai, E. S., Poltorack, O. M., Atyaksheva, L. F. (1999a). Long-lasting Effects of Chemical Exposures in Mice. In Johnston, R. E., Müller-Schwarze, D. and Sorensen, P. W (Eds.). Advances in Chemical Signals in Vertebrates (pp. 563-571). NewYork: Kluwer. doi:10.1007/978-1-4615-4733-4_50
Voznessenskaya, V. V., Wysocki, C. J., Chukhrai, E. S., Poltorack, O. M., Atyaksheva, L. F. (1999b). Is there a time during neonatal development for maximal imprinting for odor? In Johnston, R. E., Müller-Schwarze, D. and Sorensen, P. W (Eds.). Advances in Chemical Signals in Vertebrates (pp. 617-622). NewYork: Kluwer. doi:10.1007/978-1-4615-4733-4_56
Voznessenskaya, V. V., & Klyuchnikova, M. A. (2009). Induced sensitivity to androstenone: the role for main olfactory system and vomeronasal organ. Chemical Senses, 34(3), E31-32.
Voznessenskaya, V. V., Klyuchnikova, M. A., & Wysocki, C. J. (2010). Roles of the main olfactory and vomeronasal systems in the detection of androstenone in inbred strains of mice. Current Zoology, 56(6), 813-818.
Voznessenskaya, V. V., Kvasha, I. G., Klinov, A. B., Laktionova, T. K. (2016a). Responses to domestic cat chemical signals in the house mouse are modulated by early olfactory experience. In Schulte, B. A., Goodwin, T. E., Ferkin, M. H. (Eds.). Chemical Signals in Vertebrates 13 (pp. 401-411). Springer. doi:10.1007/978-3-319-22026-0_27
Voznessenskaya, V. V., Kvasha, I. G., Laktionova, T. K., Klyuchnikova, M. A. (2016b). Increased sensitivity to l-felinine in mice correlated with elevated Fos-immunoreactivity in the accessory olfactory bulb. Chemical Senses, 41(7), E89-E90.
Voznessenskaya, V. V., & Klyuchnikova, M. A. (2017). Individual variability of human olfactory sensitivity to volatile steroids: Environmental and genetic factors. Dokl Biol Sci, 473(1), 77-79. doi:10.1134/s0012496617020144
Wallrabenstein, I., Kuklan, J., Weber, L., Zborala, S., Werner, M., Altmüller, J., Hummel, T. (2013). Human trace amine-associated receptor TAAR5 can be activated by trimethylamine. PLoS ONE, 8(2), e54950. doi:10.1371/journal.pone.0054950
Wang, H. W., Wysocki, C. J., & Gold, G. H. (1993). Induction of olfactory receptor sensitivity in mice. Science, 260(5110), 998-1000. doi:10.1007/978-4-431-68355-1_93
Wang, L., Chen, L., & Jacob, T. (2004). Evidence for peripheral plasticity in human odour response. J Physiol, 554(Pt 1), 236-244. doi:10.1113/jphysiol.2003.054726
Wyart, C., Webster, W. W., Chen, J. H., Wilson, S. R., McClary, A., Khan, R. M., & Sobel, N. (2007). Smelling a single component of male sweat alters levels of cortisol in women. J of Neurosci, 27(6), 1261-1265.
Wyatt, T. D. (2015). The search for human pheromones: the lost decades and the necessity of returning to first principles. Proc Biol Sci, 282(1804), 20142994. doi:10.1098/rspb.2014.2994
Wysocki, C. J., & Beauchamp, G. K. (1984). Ability to smell androstenone is genetically determined. Proc Natl Acad Sci U S A, 81(15), 4899-4902. doi:10.1073/pnas.81.15.4899
Wysocki, C. J., & Beauchamp, G. K. (1991). Individual differences in olfaction. In Wysocki, C. J. & Kare, M. R. (Eds.) Genetics of Perception and Communications (pp. 353-373). New York: Dekker.
Wysocki, C. J., Dorries, K. M., & Beauchamp, G. K. (1989). Ability to perceive androstenone can be acquired by ostensibly anosmic people. Proc Natl Acad Sci U S A, 86(20), 7976-7978. doi:10.1073/pnas.86.20.7976
Wysocki, C. J., Whitney, G., & Tucker, D. (1977). Specific anosmia in the laboratory mouse. Behav Genet, 7(2), 171-188. doi:10.1007/bf01066005
Yee, K. K., & Wysocki, C. J. (2001). Odorant exposure increases olfactory sensitivity: olfactory epithelium is implicated. Physiol Behav, 72(5), 705-711. doi:10.1016/s0031-9384(01)00428-0
Yeshurun, Y., Sobel, N. (2010). An odor is not worth a thousand words: from multidimensional odors to unidimensional odor objects. Annu Rev Psychol, 61, 219–41. doi:10.1146/annurev.psych.60.110707.163639
Young, J. M., & Trask, B. J. (2002). The sense of smell: genomics of vertebrate odorant receptors. Hum Mol Genet, 11(10), 1153-1160. doi:10.1093/hmg/11.10.1153
Zhang, X., & Firestein, S. (2002). The olfactory receptor gene superfamily of the mouse. Nat Neurosci, 5(2), 124-133. doi:10.1038/nn800
Zhao, H., Ivic, L., Otaki, J. M., Hashimoto, M., Mikoshiba, K., & Firestein, S. (1998). Functional expression of a mammalian odorant receptor. Science, 279(5348), 237-242. doi:10.1126/science.279.5348.237
Zhuang, H., & Matsunami, H. (2007). Synergism of accessory factors in functional expression of mammalian odorant receptors. J Biol Chem, 282(20), 15284-15293. doi:10.1074/jbc.m700386200
Zozulya, S., Echeverri, F., & Nguyen, T. (2001). The human olfactory receptor repertoire. Genome Biol, 2(6), RESEARCH0018.

Share this article