Immunohistochemical Localization of Some Neurotrophic Factors and Their Receptors in the Rat Carotid Body

Dimitrinka Y. Atanasova, Nikolai E. Lazarov

Institute of Neurobiology, Bulgarian Academy of Sciences, Sofia, Bulgaria; Institute of Experimental Morphology, Pathology and Anthropology with Museum, Bulgarian Academy of Sciences, Sofia, Bulgaria.
Institute of Neurobiology, Bulgarian Academy of Sciences, Sofia, Bulgaria;Department of Anatomy and Histology, Medical University of Sofia, Sofia, Bulgaria.

DOI: 10.4236/nm.2013.44042                

Abstract

The carotid body (CB) is a small neural crest-derived organ that registers oxygen and glucose levels in blood and regulates ventilation. The most abundant cell type in the CB glomeruli is glomus or type I cells, which is enveloped by processes of sustentacular or type II cells. Growth and neurotrophic factors have been established as signaling molecules played an important role in the development of the CB. To gain insight whether these signaling molecules are present in the adult rat CB, we examined the expression and cellular localization of some neurotrophic factors and their corresponding receptors in this organ by immunohistochemistry. The results showed the presence of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) as well as p75^NTR, tyrosine kinase A receptor (TrkA), tyrosine kinase B receptor (TrkB) and GDNF family receptor alpha1 (GFRα1) in the adult CB. At the light-microscopical level, the immunoreactivity for NGF and both its low-affinity (p75) and high-affinity (TrkA) receptors was detected in the majority of glomus cells and also in a subset of sustentacular cells. BDNF and its receptors, p75 and TrkB, were observed in the glomus cells, too. Remarkably, the immunohistochemical analysis revealed that the neuron-like glomus cells, but not the glial-like sustentacular cells, expressed GDNF and GFRα1. Taken together with prior results, it can be inferred that neurotrophins may be involved in the CB cell differentiation and survival in adulthood, and may exert a potent glomic protective action as well. It is also presumable that GDNF production by glomus cells plays a pivotal role in permitting long-term viability of CB grafts, which permits their potential applicability in cell therapy as a promising tool in neurodegenerative disorders.

Keywords

Carotid Body; Immunohistochemistry; Neurotrophin Receptors; Trophic Factors; Rat

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	C. Gonzalez, L. Almaraz, A. Obeso and R. Rigual, “Carotid Body Chemoreceptors: From Natural Stimuli to Sensory Discharges,” Physiological Reviews, Vol. 74, No. 4, 1994, pp. 829-898.
[2]	C. A. Nurse and N. A. Piskuric, “Signal Processing at Mammalian Carotid Body Chemoreceptors,” Seminars in Cell & Developmental Biology, Vol. 24, No. 1, 2013, pp. 22-30. http://dx.doi.org/10.1016/j.semcdb.2012.09.006
[3]	D. Y. Atanasova, M. E. Iliev and N. E. Lazarov, “Morphology of the Rat Carotid Body,” Biomedical Reviews, Vol. 22, 2011, pp. 41-55.
[4]	C. A. Nurse, “Neurotransmission and Neuromodulation in the Chemosensory Carotid Body,” Autonomic Neuroscience, Vol. 120, No. 1-2, 2005, pp. 1-9. http://dx.doi.org/10.1016/j.autneu.2005.04.008
[5]	R. Pardal, P. Ortega-Sáenz, R. Durán and J. López-Barneo, “Glia-Like Stem Cells Sustain Physiologic Neurogenesis in the Adult Mammalian Carotid Body,” Cell, Vol. 131, No. 2, 2007, pp. 364-377. http://dx.doi.org/10.1016/j.cell.2007.07.043
[6]	J. López-Barneo, P. Ortega-Sáenz, R. Pardal, A. Pascual and J. I. Piruat, “Carotid Body Oxygen Sensing,” European Respiratory Journal, Vol. 32, No. 5, 2008, pp. 1386-1398. http://dx.doi.org/10.1183/09031936.00056408
[7]	A. Bairam and J. L. Carroll, “Neurotransmitters in Carotid Body Development,” Respiratory Physiology and Neurobiology, Vol. 149, No. 1-3, 2005, pp. 217-232. http://dx.doi.org/10.1016/j.resp.2005.04.017
[8]	R. De Caro, V. Macchi, M. M. Sfriso and A. Porzionato, “Structural and Neurochemical Changes in the Maturation of the Carotid Body,” Respiratory Physiology & Neurobiology, Vol. 185, No. 1, 2013, pp. 9-19. http://dx.doi.org/10.1016/j.resp.2012.06.012
[9]	A. Porzionato, V. Macchi, A. Parenti and R. De Caro, “Trophic Factors in the Carotid Body,” International Review of Cell & Molecular Biology, Vol. 269, 2008, pp. 1-58. http://dx.doi.org/10.1016/S1937-6448(08)01001-0
[10]	M. Yamamoto and S. Iseki, “Co-Expression of NGF and Its High-Affinity Receptor TrkA in the Rat Carotid Body Chief Cells,” Acta Histochemica et Cytochemica, Vol. 36, No. 4, 2003, pp. 377-383. http://dx.doi.org/10.1267/ahc.36.377
[11]	A. Izal-Azcárate, S. Belzunegui, W. San Sebastián, P. Garrido-Gil, M. Vázquez-Claverie, B. López, I. Marcilla and M. Luquin, “Immunohistochemical Characterization of the Rat Carotid Body,” Respiratory Physiology & Neurobiology, Vol. 161, No. 1, 2008, pp. 95-99. http://dx.doi.org/10.1016/j.resp.2007.12.008
[12]	A. B. Tonchev, T. Yamashima, J. Guo, G. N. Chaldakov and N. Takakura, “Expression of Angiogenic and Neurotrophic Factors in the Progenitor Cell Niche of Adult Monkey Subventricular Zone,“ Neuroscience, Vol. 144, No. 4, 2007, pp. 1425-1435. http://dx.doi.org/10.1016/j.neuroscience.2006.10.052
[13]	D. M. Katz, “Neuronal Growth Factors and Development of Respiratory Control,” Respiratory Physiology & Neurobiology, Vol. 135, No. 2-3, 2003, pp. 155-165. http://dx.doi.org/10.1016/S1569-9048(03)00034-X
[14]	D. M. Katz, “Regulation of Respiratory Neuron Development by Neurotrophic and Transcriptional Signaling Mechanisms,” Respiratory Physiology & Neurobiology, Vol. 149, No. 1-3, 2005, pp. 99-109. http://dx.doi.org/10.1016/j.resp.2005.02.007
[15]	Z. Y. Wang and G. E. Biscard, “Postnatal Growth of the Carotid Body,” Respiratory Physiology & Neurobiology, Vol. 149, No. 1-3, 2005, pp. 181-190. http://dx.doi.org/10.1016/j.resp.2005.03.016
[16]	E. J. Huang and L. F. Reichardt, “Neurotrophins: Roles in Neuronal Development and Function,” Annual Review of Neuroscience, Vol. 24, 2001, pp. 677-736. http://dx.doi.org/10.1146/annurev.neuro.24.1.677
[17]	A. G. E. Pearse, J. M. Polak, F. W. Rost, J. Fontaine, C. Le Lièvre and N. Le Douarin, “Demonstration of the Neural Crest Origin of Type I (APUD) Cells in the Avian Carotid Body, Using a Cytochemical Marker System,” Histochemie, Vol. 34, No. 3, 1973, pp. 191-203. http://dx.doi.org/10.1007/BF00303435
[18]	N. Le Douarin, “The Neural Crest,” Cambridge University Press, London, 1982.
[19]	M. C. Fishman and A. E. Schaffner, “Carotid Body Cell Culture and Selective Growth of Glomus Cells,” American Journal of Physiology, Vol. 246, No. 1 Pt 1, 1984, pp. C106-C113.
[20]	C. A. Nurse and C. Vollmer, “Role of Basic FCF and Oxygen in Control of Proliferation, Survival, and Neuronal Differentiation in Carotid Body Chromaffin Cells,” Developmental Biology, Vol. 184, No. 2, 1997, pp. 197-206. http://dx.doi.org/10.1006/dbio.1997.8539
[21]	R. Pardal, P. Ortega-Sáenz, R. Durán, A. Platero-Luengo and J. López-Barneo, “The Carotid Body, a Neurogenic Niche in the Adult Peripheral Nervous System,” Archives Italiennes de Biologie, Vol. 148, No. 2, 2010, pp. 95-105.
[22]	D. Atanasova and N. Lazarov, “Dopamine and Dopaminergic Innervation of the Rat Carotid Body,” Comptes Rendus de l’Académie Bulgare des Sciences, Vol. 64, No. 5, 2011, pp. 751-756.
[23]	J. J. Toledo-Aral, S. Méndez-Ferrer, R. Pardal, M. Echevarría and J. López-Barneo, “Trophic Restoration of the Nigrostriatal Dopaminergic Pathway in Long-Term Carotid Body-Grafted Parkinsonian Rats,” Journal of Neuroscience, Vol. 23, No. 1, 2003, pp. 141-148.
[24]	J. Villadiego, S. Méndez-Ferrer, T. Valdés-Sánchez, I. Silos-Santiago, I. Fariñ as, J. López-Barneo and J. J. Toledo-Aral, “Selective Glial Cell Line-Derived Neurotrophic Factor Production in Adult Dopaminergic Carotid Body Cells in Situ and after Intrastriatal Transplantation,” Journal of Neuroscience, Vol. 25, No. 16, 2005, pp. 4091-4098. http://dx.doi.org/10.1523/JNEUROSCI.4312-04.2005
[25]	J. López-Barneo, R. Pardal, P. Ortega-Sáenz, R. Durán, J. Villadiego and J. J. Toledo-Aral, “The Neurogenic Niche in the Carotid Body and Its Applicability to Antiparkinsonian Cell Therapy,” Journal of Neural Transmission, Vol. 116, No. 8, 2009, pp. 975-982. http://dx.doi.org/10.1007/s00702-009-0201-5
[26]	M. R. Luquin, M. Manrique, J. Guillén, J. Arbizu, C. Ordoñ ez and I. Marcilla, “Enhanced GDNF Expression in Dopaminergic Cells of Monkeys Grafted with Carotid Body Cell Aggregates,” Brain Research, Vol. 1375, 2011, pp. 120-127. http://dx.doi.org/10.1016/j.brainres.2010.12.033
[27]	R. Brady, S. I. Zaidi, C. Mayer and D. M. Katz, “BDNF Is a Target-Derived Survival Factor for Arterial Baroreceptor and Chemoafferent Primary Sensory Neurons,” Journal of Neuroscience, Vol. 19, No. 6, 1999, 2131-2142.
[28]	J. T. Erickson, T. A. Brosenitsch and D. M. Katz, “Brain-Derived Neurotrophic Factor and Glial Cell Line-Derived Neurotrophic Factor Are Required Simultaneously for Survival of Dopaminergic Primary Sensory Neurons in Vivo,” Journal of Neuroscience, Vol. 21, No. 2, 2001, pp. 581-589.
[29]	E. Arenas, M. Trupp, P. Akerud and C. F. Ibáñ ez, “GDNF Prevents Degeneration and Promotes the Phenotype of Brain Noradrenergic Neurons in Vivo,” Neuron, Vol. 15, No. 6, 1995, pp. 1465-1473. http://dx.doi.org/10.1016/0896-6273(95)90024-1
[30]	A. Patapoutian and L. F. Reichardt, “Trk Receptors: Mediators of Neurotrophin Action,” Current Opinion in Neurobiology, Vol. 11, No. 3, 2001, pp. 272-280. http://dx.doi.org/10.1016/S0959-4388(00)00208-7