Abstract
Due to the high importance of investigating the subfornical organ and its tissue components and mediator systems, the aim of this work was to study the morphological features of the catecholaminergic innervation of this area. Using the methods of immunohistochemistry and confocal microscopy, preparations of the rat subfornical organ were studied on postnatal days 14 and 30 and at the age of 4–6 months. The main direction of the ingrowth of catecholaminergic fibers into the subfornical organ at the early stages was determined. It was found that the processes of catecholaminergic cells can contact the cells covering the subfornical organ and can penetrate through the ependymal layer. This allows them to contact the cerebrospinal fluid directly and, presumably, affect its composition. It is shown that some of the fibers run in parallel to the basal processes of specialized ependymal cells, tanycytes, which suggests their possible function as a scaffold for growing catecholaminergic fibers in postnatal development. This is the first study to demonstrate the presence of intrinsic catecholaminergic neurons in the subfornical organ.
Similar content being viewed by others
REFERENCES
Bertler, A., Falck, B., Owman, C., and Rosengrenn, E., The localization of monoaminergic blood-brain barrier mechanisms, Pharmacol. Rev., 1966, vol. 18, p. 369. https://pubmed.ncbi.nlm.nih.gov/5904153/
Bolborea, M. and Dale, N., Hypothalamic tanycytes: potential roles in the control of feeding and energy balance, Trends Neurosci., 2013, vol. 36, p. 91. https://doi.org/10.1016/J.TINS.2012.12.008
Cenci, M.A., Presynaptic mechanisms of l-DOPA-induced dyskinesia: the findings, the debate, and the therapeutic implications, Front. Neurol., 2014, vol. 5. https://doi.org/10.3389/FNEUR.2014.00242
Dellmann, H.D. and Simpson, J.B., The subfornical organ, Int. Rev. Cytol., 1979, vol. 58, p. 333. https://doi.org/10.1016/S0074-7696(08)61479-5
Dellmann, H.D. and Stahl, S.J., Fine structural cytology of the rat subfornical organ during ontogenesis, Brain Res. Bull., 1984, vol. 13, p. 135. https://doi.org/10.1016/0361-9230(84)90015-7
Goodman, T. and Hajihosseini, M.K., Hypothalamic tanycytes-masters and servants of metabolic, neuroendocrine, and neurogenic functions, Front. Neurosci., 2015, vol. 9, p. 387. https://doi.org/10.3389/FNINS.2015.00387/BIBTEX
Hicks, A.I., Kobrinsky, S., Zhou, S., Yang, J., and Prager-Khoutorsky, M., Anatomical organization of the rat subfornical organ, Front. Cell. Neurosci., 2021, vol. 15, no. 691711. https://doi.org/10.3389/FNCEL.2021.691711
Hökfelt, T., Foster, G., Schultzberg, M., Meister, B., Schalling, M., Goldstein, M., Hemmings, H.C., Ouimet, C., and Greengard, P., DARPP-32 as a marker for D‑1 dopaminoceptive cells in the rat brain: prenatal development and presence in glial elements (tanycytes) in the basal hypothalamus, Adv. Exp. Med. Biol., 1988, vol. 235, p. 65. https://doi.org/10.1007/978-1-4899-2723-1_6
Kawai, Y., Differential ascending projections from the male rat caudal nucleus of the tractus solitarius: an interface between local microcircuits and global macrocircuits, Front. Neuroanat., 2018, vol. 12, p. 63. https://doi.org/10.3389/FNANA.2018.00063/BIBTEX
Kawano, H. and Masuko, S., Tyrosine hydroxylase-immunoreactive projections from the caudal ventrolateral medulla to the subfornical organ in the rat, Brain Res., 2001, vol. 903, p. 154. https://doi.org/10.1016/S0006-8993(01)02435-0
Korzh, V. and Kondrychyn, I., Origin and development of circumventricular organs in living vertebrate, Semin. Cell Dev. Biol., 2020, vol. 102, p. 13. https://doi.org/10.1016/J.SEMCDB.2019.10.010
Korzhevskii, D.E., Sukhorukova, E.G., Kirik, O.V., and Grigorev, I.P., Immunohistochemical demonstration of specific antigens in the human brain fixed in zinc-ethanol-formaldehyde, Eur. J. Histochem., 2015, vol. 59, p. 5. https://doi.org/10.4081/EJH.2015.2530
Langlet, F., Mullier, A., Bouret, S.G., Prevot, V., and Dehouck, B., Tanycyte-like cells form a blood-cerebrospinal fluid barrier in the circumventricular organs of the mouse brain, J. Comp. Neurol., 2013, vol. 521, p. 3389. https://doi.org/10.1002/CNE.23355
Lind, R.W., van Hoesen, G.W., and Johnson, A.K., An HRP study of the connections of the subfornical organ of the rat, J. Comp. Neurol., 1982, vol. 210, p. 265. https://doi.org/10.1002/CNE.902100306
Lorez, H.P. and Richards, J.G., Supra-ependymal serotoninergic nerves in mammalian brain: morphological, pharmacological and functional studies, Brain Res. Bull., 1982, vol. 9, p. 727. https://doi.org/10.1016/0361-9230(82)90179-4
McKinley, M.J., McAllen, R.M., Davern, P., Giles, M.E., Penschow, J., Sunn, N., Uschakov, A., and Oldfield, B.J., The sensory circumventricular organs of the mammalian brain, Adv. Anat. Embryol. Cell Biol., 2003, vol. 172, p. 1. https://doi.org/10.1007/978-3-642-55532-9
Meister, B., Hökfelt, T., Tsuruo, Y., Hemmings, H., Oui-met, C., Greengard, P., and Goldstein, M., DARPP-32, a dopamine- and cyclic AMP-regulated phosphoprotein in tanycytes of the mediobasal hypothalamus: distribution and relation to dopamine and luteinizing hormone-releasing hormone neurons and other glial elements, Neuroscience, 1988, vol. 27, p. 607. https://doi.org/10.1016/0306-4522(88)90292-8
Miyahara, N., Ono, K., Hitomi, S., Hirase, M., and Inenaga, K., Dopamine modulates neuronal excitability pre- and post-synaptically in the rat subfornical organ, Brain Res., 2012, vol. 1447, p. 44. https://doi.org/10.1016/J.BRAINRES.2012.01.063
Moini, J. and Piran, P., Limbic, olfactory, and gustatory systems, in Functional and Clinical Neuroanatomy, London: Academic Press, 2020, p. 467. https://doi.org/10.1016/B978-0-12-817424-1.00015-X
Murtazina, A.R., Bondarenko, N.S., Pronina, T.S., Chandran, K.I., Bogdanov, V.V., Dilmukhametova, L.K., and Ugrumov, M.V., A comparative analysis of CSF and the blood levels of monoamines as neurohormones in rats during ontogenesis, Acta Nat., 2021, vol. 13, no. 4, p. 89. https://doi.org/10.32607/actanaturae.11516
Pulman, K.J., Fry, W.M., Cottrell, G.T., and Ferguson, A.V., The subfornical organ: a central target for circulating feeding signals, J. Neurosci., 2006, vol. 26, p. 2022. https://doi.org/10.1523/JNEUROSCI.3218-05.2006
Richards, J.G., Lorez, H.P., Colombo, V.E., Guggenheim, R., Kiss, D., and Wu, J.Y., Demonstration of supra-ependymal 5-HT nerve fibres in human brain and their immunohistochemical identification in rat brain, J. Physiol. (Paris, 1946–1992), 1981, vol. 77, p. 219. https://pubmed.ncbi.nlm.nih.gov/ 7026769/
Rosas-Arellano, M.P., Solano-Flores, L.P., and Ciriello, J., Arcuate nucleus inputs onto subfornical organ neurons that respond to plasma hypernatremia and angiotensin II, Brain Res., 1996, vol. 707, p. 308. https://doi.org/10.1016/0006-8993(95)01368-7
Sufieva, D.A., Kirik, O. V., and Korzhevskii, D.E., Nucleolin and nucleoli in ependymocytes and tanycytes of the third ventricle of the rat brain, Cell Tissue Biol., 2018, vol. 12, no. 2, p. 167. https://doi.org/1134/S1990519X18020116
Takahashi, M. and Tanaka, J., Noradrenaline receptor mechanisms modulate the angiotensin II-induced water intake in the subfornical organ in rats, Exp. Brain Res., 2017, vol. 235, p. 833. https://doi.org/10.1007/S00221-016-4844-9
Tanaka, J. and Seto, K., Neurons in the lateral hypothalamic area and zona incerta with ascending projections to the subfornical organ area in the rat, Brain Res., 1988, vol. 456, p. 397. https://doi.org/10.1016/0006-8993(88)90247-8
Tanaka, J., Hayashi, Y., Shimamune, S., and Nomura, M., Ascending pathways from the nucleus of the solitary tract to the subfornical organ in the rat, Brain Res., 1997, vol. 777, p. 237. https://doi.org/10.1016/S0006-8993(97)01211-0
Tsukashima, A., Tsuchihashi, T., Abe, I., Nakamura, K., Uchimura, H., and Fujishima, M., Angiotensin II increases norepinephrine turnover in the anteroventral third ventricle of spontaneously hypertensive rats, Hypertension, 1996, vol. 28, p. 224. https://doi.org/10.1161/01.HYP.28.2.224
Ugrumov, M.V., Monoamine synthesis by non-monoaminergic neurons: illusion or reality, Ross. Fiziol. Zh. im. I.M. Sechenova, 2009, vol. 95, p. 273.
Vígh, B., Manzano e Silva, M.J., Frank, C.L., Vincze, C., Czirok, S.J., Szabó, A., Lukáts, A., and Szél, A., The system of cerebrospinal fluid-contacting neurons. Its supposed role in the nonsynaptic signal transmission of the brain, Histol. Histopathol., 2004, vol. 19, p. 607. https://doi.org/10.14670/HH-19.607
Zheng, Z., Chopp, M., and Chen, J., Multifaceted roles of pericytes in central nervous system homeostasis and disease, J. Cereb. Blood Flow Metab., 2020, vol. 40, p. 1381. https://doi.org/10.1177/0271678X20911331
Zimmerman, C.A., Lin, Y.C., Leib, D.E., Guo, L., Huey, E.L., Daly, G.E., Chen, Y., and Knight, Z.A., Thirst neurons anticipate the homeostatic consequences of eating and drinking, Nature, 2016, vol. 537, p. 680. https://doi.org/10.1038/NATURE18950
Zimmerman, C.A., Huey, E.L., Ahn, J.S., Beutler, L.R., Tan, C.L., Kosar, S., Bai, L., Chen, Y., Corpuz, T.V., Madisen, L., Zeng, H., and Knight, Z.A., A gut-to-brain signal of fluid osmolarity controls thirst satiation, Nature, 2019, vol. 568, p. 98. https://doi.org/10.1038/S41586-019-1066-X
Funding
The reported study was funded by RSF according to the research project № 22-25-00105, https://rscf.ru/project/ 22-25-00105/
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest. The authors declare that they have no conflicts of interest.
Statement on the welfare of animals. All procedures involving animals were carried out in accordance with the guidelines established by the Directive 86/609/EEC on the protection of Animals used for Experimental and other scientific purposes (Strasbourg, 1986) and the Rules of Good Laboratory Practice (order no. 199n of the Russian Ministry of Health dated April 1, 2016). The study was approved by the Local Ethics Committee of the Institute of Experimental Medicine, conclusion no. 1/22 dated February 18, 2022.
Additional information
Translated by M. Batrukova
Abbreviations: BBB—blood–brain barrier; SFO—subfornical organ; TH—tyrosine hydroxylase; CSF—cerebrospinal fluid.
Rights and permissions
About this article
Cite this article
Razenkova, V.A., Korzhevskii, D.E. Catecholaminergic Structures of the Rat Subfornical Organ. Cell Tiss. Biol. 16, 568–575 (2022). https://doi.org/10.1134/S1990519X22060062
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S1990519X22060062