Yetişkin Memeli Beyninde Nörogenez ve Koku Duyusu ile İlişkisi

Yıl 2024, Cilt: 8 Sayı: 1, 35 - 56, 30.04.2024

Oğuzhan Ekici Gönül Şimşek

https://doi.org/10.33716/bmedj.1444256

Öz

Amaç: Bu derlemenin amacı; beyindeki nörogenez merkezleri, bu merkezlerin mikro mimarisi, nörogenezi etkileyen faktörleri, nöroblastların göç etmeleri, farklılaşmaları ve olgun nöron oluşturma mekanizmaları hakkında bilgiler sunmaktadır. İnsan ve diğer memeliler arasındaki farklara değinilerek nörogenez ve koku duyusu arasındaki ilişkinin incelenmesi amaçlanmıştır. Gereç ve Yöntem: Bu çalışma, yetişkin memeli beyninde nörogenez ve koku duyusu hakkında literatür taraması yapılarak derlenmiştir. Bulgular: Nörogenez, kök hücrelerin bölünüp farklılaşarak yeni nöron üretmesidir. Yetişkin memeli beyninde nörogenezin varlığı gösterilmiştir. Beyinde, Subventriküler zon (SVZ) ve Subgranüler zon (SGZ) iki ana nöral kök hücre topluluğu olarak bilinmektedir. Bu bölgelerdeki nöral kök hücreler bölünüp farklılaşarak nöroblastları meydana getirmektedir. Nöroblastlar göç ederek hedef bölgelerinde olgun nöron halini almaktadırlar. SVZ’de üretilen nöroblastlar olfaktör bulbusta, SGZ’de üretilenler ise hipokampusun granüler katmanında olgun nöron olarak işlev görmektedir. Koku duyusu, burunda olfaktör epitelde başlamaktadır. Olfaktör epitelde koku molekülleri, kendilerine özgü reseptörlerine bağlanarak, olfaktör duyu nöronlarında sinirsel uyarıyı başlatmaktadır. Sinirsel uyarı beyinde önce olfaktör bulbusta işlenmekte daha sonra koku merkezlerine iletilmektedir. Koku bilgisinin iletildiği yapılar arasında; priform korteks, ön koku alma çekirdeği, koku alma tüberkülü, amigdala, hipotalamus, orbitofrontal korteks, entorinal korteks ve hipokampus bulunmaktadır. Sonuç: Yetişkin memeli beyninde nörogenez ile meydana gelen yeni nöronlar, koku duyusu alanları ile doğrudan veya dolaylı olarak bağlantı kurmaktadır. Yeni nöronlar olfaktör bulbusta ara nöron halini alarak doğrudan koku duyusuyla ilişki kurarken, hipokampustaki yeni nöronlar koku hafızası oluşumunda dolaylı olarak katkı sağlamaktadır.

Anahtar Kelimeler

nörogenez, koku alma sistemi, beyin, kök hücre

Neurogenesis in the Adult Mammalian Brain and Its Relationship to the Sense of Smell

Öz

Objectives: The aim of this review is to provide information about neurogenesis centers in the brain, microarchitecture of these centers, factors affecting neurogenesis, migration and differentiation of neuroblasts and mechanisms of mature neuron formation. It is aimed to examine the relationship between neurogenesis and the sense of smell by mentioning the differences between humans and other mammals. Material and Methods: This study was compiled by reviewing the literature on neurogenesis and the sense of smell in the adult mammalian brain. Results: Neurogenesis is the production of new neurons by stem cells dividing and differentiating. The existence of neurogenesis has been demonstrated in the adult mammalian brain. In the brain, Subventricular zone (SVZ) and Subgranular zone (SGZ) are known as two main neural stem cell populations. Neural stem cells in these regions divide and differentiate to form neuroblasts. Neuroblasts migrate and become mature neurons in their target areas. Neuroblasts produced in the SVZ function as mature neurons in the olfactory bulb, and those produced in the SGZ function as mature neurons in the granular layer of the hippocampus. The sense of smell begins in the olfactory epithelium in the nose. In the olfactory epithelium, odor molecules bind to their specific receptors and initiate neural stimulation in olfactory sensory neurons. The neural stimulus is first processed in the olfactory bulb in the brain and then transmitted to the olfactory centers. Among the structures through which odor information is transmitted, pyriform cortex, anterior olfactory nucleus, olfactory tubercle, amygdala, hypothalamus, orbitofrontal cortex, entorhinal cortex and hippocampus. Conclusion: New neurons formed through neurogenesis in the adult mammalian brain establish direct or indirect connections with olfactory areas. While new neurons become interneurons in the olfactory bulb and directly establish a relationship with the sense of smell, new neurons in the hippocampus indirectly contribute to the formation of olfactory memory.

Anahtar Kelimeler

Neurogenesis, Oldfactory System, Brain, Stem Cell

Kaynakça

• Ables, J. L., Breunig, J. J., Eisch, A. J., & Rakic, P. (2011). Not(ch) just development: Notch signalling in the adult brain. Nature reviews. Neuroscience, 12(5), 269–283. https://doi.org/10.1038/nrn3024
• Adams, W., Graham, J. N., Han, X., & Riecke, H. (2019). Top-down inputs drive neuronal network rewiring and context-enhanced sensory processing in olfaction. PLoS computational biology, 15(1), e1006611. https://doi.org/10.1371/journal.pcbi.1006611
• Azadian, M. M., & George, P. M. (2023). Neurogenesis. Reference Module in Neuroscience and Biobehavioral Psychology. Elsevier. doi.org/10.1016/B978-0-12-820480-1.00040-1.
• Bartkowska, K., Turlejski, K., Koguc-Sobolewska, P., & Djavadian, R. (2023). Adult neurogenesis in the mammalian hypothalamus: impact of newly generated neurons on hypothalamic function. Neuroscience, doi.org/10.1016/j.neuroscience.2023.02.012.
• Breton-Provencher, V., & Saghatelyan, A. (2012). Newborn neurons in the adult olfactory bulb: unique properties for specific odor behavior. Behavioural brain research, 227(2), 480–489. https://doi.org/10.1016/j.bbr.2011.08.001
• Carvalho, M. M., Tanke, N., Kropff, E., Witter, M. P., Moser, B., & Moser, E. I. (2020). A Brainstem Locomotor Circuit Drives the Activity of Speed Cells in the Medial Entorhinal Cortex. Cell Reports, 32(10). https://doi.org/10.1016/j.celrep.2020.108123
• Chang, E. H., Adorjan, I., Mundim, M. V., Sun, B., Dizon, M. L., & Szele, F. G. (2016). Traumatic Brain Injury Activation of the Adult Subventricular Zone Neurogenic Niche. Frontiers in neuroscience, 10, 332. https://doi.org/10.3389/fnins.2016.00332
• Chen, P., Guo, Z., & Zhou, B. (2023). Insight into the role of adult hippocampal neurogenesis in aging and Alzheimer's disease. Ageing research reviews, 84, 101828. https://doi.org/10.1016/j.arr.2022.101828
• Coelho, P., Fão, L., Mota, S., & Rego, A. C. (2022). Mitochondrial function and dynamics in neural stem cells and neurogenesis: Implications for neurodegenerative diseases. Ageing research reviews, 80, 101667. https://doi.org/10.1016/j.arr.2022.101667
• Delgado, A. C., Ferrón, S. R., Vicente, D., Porlan, E., Perez-Villalba, A., Trujillo, C. M., D'Ocón, P., & Fariñas, I. (2014). Endothelial NT-3 delivered by vasculature and CSF promotes quiescence of subependymal neural stem cells through nitric oxide induction. Neuron, 83(3), 572–585. https://doi.org/10.1016/j.neuron.2014.06.015
• Dityatev, A., Seidenbecher, C. I., & Schachner, M. (2010). Compartmentalization from the outside: the extracellular matrix and functional microdomains in the brain. Trends in neurosciences, 33(11), 503–512. https://doi.org/10.1016/j.tins.2010.08.003
• Favaro, R., Valotta, M., Ferri, A. L., Latorre, E., Mariani, J., Giachino, C., Lancini, C., Tosetti, V., Ottolenghi, S., Taylor, V., & Nicolis, S. K. (2009). Hippocampal development and neural stem cell maintenance require Sox2-dependent regulation of Shh. Nature neuroscience, 12(10), 1248–1256. https://doi.org/10.1038/nn.2397
• García-Marqués, J., De Carlos, J. A., Greer, C. A., & López-Mascaraque, L. (2010). Different astroglia permissivity controls the migration of olfactory bulb interneuron precursors. Glia, 58(2), 218–230. https://doi.org/10.1002/glia.20918
• Gault, N., & Szele, F. G. (2021). Immunohistochemical evidence for adult human neurogenesis in health and disease. WIREs mechanisms of disease, 13(6), e1526. https://doi.org/10.1002/wsbm.1526
• Ge, H., Hu, Q., Chen, T., Yang, Y., Zhang, C., Zhong, J., Yin, Y., Jiang, X., Zhou, X., Wang, S., Hu, R., Li, W., & Feng, H. (2022). Transplantation of layer-by-layer assembled neural stem cells tethered with vascular endothelial growth factor reservoir promotes neurogenesis and angiogenesis after ischemic stroke in mice. Applied Materials Today, 28, 101548. https://doi.org/10.1016/j.apmt.2022.101548
• Imamura, F., Ito, A., & LaFever, B. J. (2020). Subpopulations of Projection Neurons in the Olfactory Bulb. Frontiers in Neural Circuits, 14. https://doi.org/10.3389/fncir.2020.561822
• Iversen, K., Beaubien, F., Prince, J. E., & Cloutier, J. (2019). Axon guidance: Slit–Robo signaling. Cellular Migration and Formation of Axons and Dendrites (Second Edition), 147-173. https://doi.org/10.1016/B978-0-12-814407-7.00007-9
• Johansson, C. B., Momma, S., Clarke, D. L., Risling, M., Lendahl, U., & Frisén, J. (1999). Identification of a neural stem cell in the adult mammalian central nervous system. Cell, 96(1), 25–34. https://doi.org/10.1016/s0092-8674(00)80956-3
• Jurkowski, M. P., Bettio, L., Patten, A., & Yau, S. (2020). Beyond the Hippocampus and the SVZ: Adult Neurogenesis Throughout the Brain. Frontiers in Cellular Neuroscience, 14, 576444. https://doi.org/10.3389/fncel.2020.576444
• Kaneko, N., Marín, O., Koike, M., Hirota, Y., Uchiyama, Y., Wu, J. Y., Lu, Q., Tessier-Lavigne, M., Alvarez-Buylla, A., Okano, H., Rubenstein, L. R., & Sawamoto, K. (2010). New Neurons Clear the Path of Astrocytic Processes for Their Rapid Migration in the Adult Brain. Neuron, 67(2), 213. https://doi.org/10.1016/j.neuron.2010.06.018.
• Kaneko, N., Sawada, M., & Sawamoto, K. (2017). Mechanisms of neuronal migration in the adult brain. Journal of neurochemistry, 141(6), 835–847. https://doi.org/10.1111/jnc.14002
• Karalay, O., Doberauer, K., Vadodaria, K. C., Knobloch, M., Berti, L., Miquelajauregui, A., Schwark, M., Jagasia, R., Taketo, M. M., Tarabykin, V., Lie, D. C., & Jessberger, S. (2011). Prospero-related homeobox 1 gene (Prox1) is regulated by canonical Wnt signaling and has a stage-specific role in adult hippocampal neurogenesis. Proceedings of the National Academy of Sciences of the United States of America, 108(14), 5807–5812. https://doi.org/10.1073/pnas.1013456108
• Kharlamova, A. S., Godovalova, O. S., Otlyga, E. G., & Proshchina, A. E. (2023). Primary and secondary olfactory centres in human ontogeny. Neuroscience research, 190, 1–16. https://doi.org/10.1016/j.neures.2022.12.005
• Kippin, T. E., Kapur, S., & van der Kooy, D. (2005). Dopamine specifically inhibits forebrain neural stem cell proliferation, suggesting a novel effect of antipsychotic drugs. The Journal of neuroscience: the official journal of the Society for Neuroscience, 25(24), 5815–5823. https://doi.org/10.1523/JNEUROSCI.1120-05.2005
• Kirschenbaum, B., Doetsch, F., Lois, C., & Alvarez-Buylla, A. (1999). Adult subventricular zone neuronal precursors continue to proliferate and migrate in the absence of the olfactory bulb. The Journal of neuroscience: the official journal of the Society for Neuroscience, 19(6), 2171–2180. https://doi.org/10.1523/JNEUROSCI.19-06-02171.1999
• Kuhn, H. G., Biebl, M., Wilhelm, D., Li, M., Friedlander, R. M., & Winkler, J. (2005). Increased generation of granule cells in adult Bcl-2-overexpressing mice: a role for cell death during continued hippocampal neurogenesis. The European journal of neuroscience, 22(8), 1907–1915. https://doi.org/10.1111/j.1460-9568.2005.04377.x
• Lehtinen, M. K., Zappaterra, M. W., Chen, X., Yang, Y. J., Hill, A. D., Lun, M., Maynard, T., Gonzalez, D., Kim, S., Ye, P., D'Ercole, A. J., Wong, E. T., LaMantia, A. S., & Walsh, C. A. (2011). The cerebrospinal fluid provides a proliferative niche for neural progenitor cells. Neuron, 69(5), 893–905. https://doi.org/10.1016/j.neuron.2011.01.023
• Lepousez, G., & Lledo, P. M. (2013). Odor discrimination requires proper olfactory fast oscillations in awake mice. Neuron, 80(4), 1010–1024. https://doi.org/10.1016/j.neuron.2013.07.025
• Li, W. L., Chu, M. W., Wu, A., Suzuki, Y., Imayoshi, I., & Komiyama, T. (2018). Adult-born neurons facilitate olfactory bulb pattern separation during task engagement. eLife, 7, e33006. https://doi.org/10.7554/eLife.33006
• Lim, D. A., & Alvarez-Buylla, A. (2016). The Adult Ventricular–Subventricular Zone (V-SVZ) and Olfactory Bulb (OB) Neurogenesis. Cold Spring Harbor Perspectives in Biology, 8(5). https://doi.org/10.1101/cshperspect.a018820.
• Lindvall, O., & Kokaia, Z. (2015). Neurogenesis following Stroke Affecting the Adult Brain. Cold Spring Harbor perspectives in biology, 7(11), a019034. https://doi.org/10.1101/cshperspect.a019034
• Lledo, P. M., & Valley, M. (2016). Adult Olfactory Bulb Neurogenesis. Cold Spring Harbor perspectives in biology, 8(8), a018945. https://doi.org/10.1101/cshperspect.a018945
• Mandairon, N., Jourdan, F., & Didier, A. (2003). Deprivation of sensory inputs to the olfactory bulb up-regulates cell death and proliferation in the subventricular zone of adult mice. Neuroscience, 119(2), 507–516. https://doi.org/10.1016/s0306-4522(03)00172-6
• Mercier, F., Kitasako, J. T., & Hatton, G. I. (2002). Anatomy of the brain neurogenic zones revisited: fractones and the fibroblast/macrophage network. The Journal of comparative neurology, 451(2), 170–188. https://doi.org/10.1002/cne.10342
• Mirzadeh, Z., Merkle, F. T., Soriano-Navarro, M., Garcia-Verdugo, J. M., & Alvarez-Buylla, A. (2008). Neural stem cells confer unique pinwheel architecture to the ventricular surface in neurogenic regions of the adult brain. Cell stem cell, 3(3), 265–278. https://doi.org/10.1016/j.stem.2008.07.004
• Moreno-Jiménez, E. P., Terreros-Roncal, J., Flor-García, M., Rábano, A., & Llorens-Martín, M. (2021). Evidences for Adult Hippocampal Neurogenesis in Humans. The Journal of neuroscience: the official journal of the Society for Neuroscience, 41(12), 2541–2553. https://doi.org/10.1523/JNEUROSCI.0675-20.2020
• Morita, M., Kozuka, N., Itofusa, R., Yukawa, M., & Kudo, Y. (2005). Autocrine activation of EGF receptor promotes oscillation of glutamate-induced calcium increase in astrocytes cultured in rat cerebral cortex. Journal of neurochemistry, 95(3), 871–879. https://doi.org/10.1111/j.1471-4159.2005.03430.x
• Nachtergaele, S., Whalen, D. M., Mydock, L. K., Zhao, Z., Malinauskas, T., Krishnan, K., Ingham, P. W., Covey, D. F., Siebold, C., & Rohatgi, R. (2013). Structure and function of the Smoothened extracellular domain in vertebrate Hedgehog signaling. ELife, 2. https://doi.org/10.7554/eLife.01340
• Ng, K. L., Li, J. D., Cheng, M. Y., Leslie, F. M., Lee, A. G., & Zhou, Q. Y. (2005). Dependence of olfactory bulb neurogenesis on prokineticin 2 signaling. Science (New York, N.Y.), 308(5730), 1923–1927. https://doi.org/10.1126/science.1112103
• Nogueira, A. B., Sogayar, M. C., Colquhoun, A., Siqueira, S. A., Nogueira, A. B., Marchiori, P. E., & Teixeira, M. J. (2014). Existence of a potential neurogenic system in the adult human brain. Journal of Translational Medicine, 12, 75. https://doi.org/10.1186/1479-5876-12-75
• Nogueira, A. B., Hoshino, H. S. R., Ortega, N. C., Dos Santos, B. G. S., & Teixeira, M. J. (2022). Adult human neurogenesis: early studies clarify recent controversies and go further. Metabolic brain disease, 37(1), 153–172. https://doi.org/10.1007/s11011-021-00864-8
• Obernier, K., & Alvarez-Buylla, A. (2019). Neural stem cells: origin, heterogeneity and regulation in the adult mammalian brain. Development (Cambridge, England), 146(4), dev156059. https://doi.org/10.1242/dev.156059.
• Oddi, S., Fiorenza, M. T., & Maccarrone, M. (2023). Endocannabinoid signaling in adult hippocampal neurogenesis: A mechanistic and integrated perspective. Progress in lipid research, 91, 101239. https://doi.org/10.1016/j.plipres.2023.101239
• Paul, A., Chaker, Z., & Doetsch, F. (2017). Hypothalamic regulation of regionally distinct adult neural stem cells and neurogenesis. Science (New York, N.Y.), 356(6345), 1383–1386. https://doi.org/10.1126/science.aal3839
• Persson, B. M., Ambrozova, V., Duncan, S., Wood, E. R., O'Connor, A. R., & Ainge, J. A. (2022). Lateral entorhinal cortex lesions impair odor-context associative memory in male rats. Journal of neuroscience research, 100(4), 1030–1046. https://doi.org/10.1002/jnr.25027
• Petreanu, L., & Alvarez-Buylla, A. (2002). Maturation and death of adult-born olfactory bulb granule neurons: role of olfaction. The Journal of neuroscience: the official journal of the Society for Neuroscience, 22(14), 6106–6113. https://doi.org/10.1523/JNEUROSCI.22-14-06106.2002
• Platel, C., Dave, K. A., Gordon, V., Lacar, B., Rubio, M. E., & Bordey, A. (2010). NMDA receptors activated by subventricular zone astrocytic glutamate are critical for neuroblast survival prior to entering a synaptic network. Neuron, 65(6), 859. https://doi.org/10.1016/j.neuron.2010.03.009
• Price, J. L. (2009). Olfactory Higher Centers Anatomy. In Encyclopedia of Neuroscience (pp. 129-136). Elsevier Ltd. https://doi.org/10.1016/B978-008045046-9.01692-2
• Ryan, S. M., & Kelly, Á. M. (2016). Exercise as a pro-cognitive, pro-neurogenic and anti-inflammatory intervention in transgenic mouse models of Alzheimer's disease. Ageing research reviews, 27, 77–92. https://doi.org/10.1016/j.arr.2016.03.007
• Sakai J. (2020). Core Concept: How synaptic pruning shapes neural wiring during development and, possibly, in disease. Proceedings of the National Academy of Sciences of the United States of America, 117(28), 16096–16099. https://doi.org/10.1073/pnas.2010281117
• Shingo, T., Gregg, C., Enwere, E., Fujikawa, H., Hassam, R., Geary, C., Cross, J. C., & Weiss, S. (2003). Pregnancy-stimulated neurogenesis in the adult female forebrain mediated by prolactin. Science (New York, N.Y.), 299(5603), 117–120. https://doi.org/10.1126/science.1076647
• Shinohara, R., Thumkeo, D., Kamijo, H., Kaneko, N., Sawamoto, K., Watanabe, K., Takebayashi, H., Kiyonari, H., Ishizaki, T., Furuyashiki, T., & Narumiya, S. (2012). A role for mDia, a Rho-regulated actin nucleator, in tangential migration of interneuron precursors. Nature neuroscience, 15(3), 373–S2. https://doi.org/10.1038/nn.3020
• Sorrells, S. F., Paredes, M. F., Cebrian-Silla, A., Sandoval, K., Qi, D., Kelley, K. W., James, D., Mayer, S., Chang, J., Auguste, K. I., Chang, E. F., Gutierrez, A. J., Kriegstein, A. R., Mathern, G. W., Oldham, M. C., Huang, E. J., Garcia-Verdugo, J. M., Yang, Z., & Alvarez-Buylla, A. (2018). Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults. Nature, 555(7696), 377–381. https://doi.org/10.1038/nature25975
• Tan, X. D., Liu, B., Jiang, Y., Yu, H. J., & Li, C. Q. (2021). Gadd45b mediates environmental enrichment-induced neurogenesis in the SVZ of rats following ischemia stroke via BDNF. Neuroscience letters, 745, 135616. https://doi.org/10.1016/j.neulet.2020.135616
• Tong, C. K., Chen, J., Cebrián-Silla, A., Mirzadeh, Z., Obernier, K., Guinto, C. D., Tecott, L. H., García-Verdugo, J. M., Kriegstein, A., & Alvarez-Buylla, A. (2014). Axonal control of the adult neural stem cell niche. Cell stem cell, 14(4), 500–511. https://doi.org/10.1016/j.stem.2014.01.014
• Ünal, G. (2019). The Cortico-hippocampal Circuit: The Brain’s Center for Mapping and Declarative Memory, Ankara Üniversitesi Tıp Fakültesi Mecmuası, 72(1), 13-23. https://doi.org/10.4274/atfm.galenos.2019.58077
• Yagita, Y., Sakurai, T., Tanaka, H., Kitagawa, K., Colman, D. R., & Shan, W. (2009). N-cadherin mediates interaction between precursor cells in the subventricular zone and regulates further differentiation. Journal of Neuroscience Research, 87(15), 3331-3342. https://doi.org/10.1002/jnr.22044
• Yan, Y. P., Sailor, K. A., Lang, B. T., Park, S. W., Vemuganti, R., & Dempsey, R. J. (2007). Monocyte chemoattractant protein-1 plays a critical role in neuroblast migration after focal cerebral ischemia. Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism, 27(6), 1213–1224. https://doi.org/10.1038/sj.jcbfm.9600432
• Yang, D., Li, Q., Fang, L., Cheng, K., Zhang, R., Zheng, P., Zhan, Q., Qi, Z., Zhong, S., & Xie, P. (2011). Reduced neurogenesis and pre-synaptic dysfunction in the olfactory bulb of a rat model of depression. Neuroscience, 192, 609–618. https://doi.org/10.1016/j.neuroscience.2011.06.043
• Ye, Z., Wang, J., Fang, F., Wang, Y., Liu, Z., Shen, C., & Hu, Y. (2024). Zhi-Zi-Hou-Po decoction alleviates depressive-like behavior and promotes hippocampal neurogenesis in chronic unpredictable mild stress induced mice via activating the BDNF/TrkB/CREB pathway. Journal of ethnopharmacology, 319(Pt3), 117355. https://doi.org/10.1016/j.jep.2023.117355