CO5: Neurogenesis and Neuroregeneration

Our group studies the molecular and cellular mechanisms that regulate neurogenesis in the adult brain with the idea of promoting the regeneration of traumatic, vascular or neurodegenerative brain injuries. Neuronal death caused by injuries of any etiology such as trauma, ischemic cerebrovascular accidents, neurodegenerative diseases, etc. It is an irreversible process and still without effective treatment. The discovery of neural stem cells in the adult brain has opened up the possibility of developing new therapies in regenerative medicine based on neuronal replacement from neural stem cells (neurogenesis). Under physiological conditions, there is neurogenesis in two areas of the adult brain. However, in lesions they form very few new neurons. The problem is that there are signaling molecules in the environment of the lesion that activate intracellular signaling pathways that prevent the formation of new neurons. Thus, establishing which molecules and signaling pathways promote neurogenesis and trying to modulate their activity can contribute to regenerating the damaged nervous system. Our laboratory has recently shown that the regulation of the ADAM17/TGFalpha/EGFR signaling pathway in mechanical lesions of the cerebral cortex can have a neurogenic effect. For this reason, we are looking for small molecules that, acting on this signaling pathway, allow the generation of functional neurons in damaged regions of the adult brain, which integrate into pre-existing circuits. These molecules may form the basis for the development of drugs that facilitate the functional regeneration of brain lesions.

• Carmen Castro González:
• e-mail: carmen.castro@uca.es.
• ORCID: 0000-0001-6802-0572.

• Hyperhomocysteinemia and dementia: effects of plasma homocysteine levels on neurogenesis in the adult brain.
• Regeneration of brain lesions: role of ADAM17 on neuron formation in cortical lesions.
• Search for non-tumorogenic PKC activators to facilitate functional regeneration of brain lesions.
• Role of PKC in the development of Glioblastoma.
• Role of Inflammation in ENACH pathology.

Neurogenesis Neuroregeneration Molecular and cellular mechanisms

• Principal Investigators:
  • Carmen Castro González - University Professor (PI).
• Investigators:
  • Noelia Geribaldi Doldán - Temporary Substitute Teacher.
  • Cristina Verástegui Escolano - University Professor.
  • José Luis Gil Salú - Area specialist facultative.
  • Irene Iglesias Lozano - Area specialist facultative.
• Postdoctoral Researchers:
  • José María Oliva Montero.
  • Ricardo Pardillo Díaz.
  • Samuel Domínguez García (Margarita Salas Postdoctoral Researcher).
  • Carlos Bernal (Margarita Salas Postdoctoral Researcher).
• Predoctoral Researchers:
  • Ricardo Gómez Oliva (Predoctoral Researcher in training).
  • Patricia Pérez García (Predoctoral Researcher in training).
• Associate Researchers:
  • Pedro Núñez Abades - Catedrático de Universidad (Principal Investigator - University of Seville).
  • Livia Carrascal Moreno - Profesora Titular de Universidad (Principal Investigator - University of Seville).
• Research Support Staff:
  • Sergio Martínez Ortega (Specialist Technician).

• Plan Nacional de I+D convocatoria Retos 2018 MICINN RTI2018-099908-B-C21 PI: Carmen Castro González. Terapias de reemplazo neuronal en dos modelos animales de daño cerebal: hacia la búsqueda de nuevos fármacos (REMIND).
• Plan Nacional de I+D convocatoria Retos 2015 MINECO BFU2015-68652-R PI: Carmen Castro González. Regeneración de lesiones traumáticas de la corteza cerebral mediante moduladores de PKC.

• Consejería de Salud y Familia -ITI. Junta de Andalucía. ITI-0042-2019 PI: Carmen Castro González. Búsqueda de nuevos Fármacos par el tratamiento del GlioblasToma Humano (FiGHT).
• Consejería de Salud y Familia -ITI. Junta de Andalucía. FEDER-UCA18-106647 PI: Carmen Castro González. Regeneración De Lesiones Cerebrales Mediante Reguladores De La Vía PKC/ADAM17/EGFR: hacia el Diseño De Nuevos Fármacos (Repare).
• Consejería de Salud y Familia. Junta de Andalucía. PIN-0191-2018 PI: Irene Iglesias Lozano. Incorporación Del Neuropsicólogo Al Equipo Multidisciplinar En La Cirugía En Paciente Despierto (CPD).
• Plan Nacional de I+D convocatoria Retos 2015 MINECO BFU2015-68652-R PI: Carmen Castro González. Regeneración de lesiones traumáticas de la corteza cerebral mediante moduladores de PKC.

• Ministerio de Universidades, FPI. PI: Patricia Pérez García.
• Ministerio de Ciencia e Innovación, Margarita Salas. PI: Samuel Domínguez García.
• Ministerio de Ciencia e Innovación, Margarita Salas. PI: Carlos Bernal Utrera.

1. Perez-Garcia P, Pardillo-Díaz R, Geribaldi-Doldán N, Gómez-Oliva R, Domínguez-García S, Castro, C; Nunez-Abades P, and Carrascal L. Refinement of active and passive membrane properties of layer V pyramidal neurons in rat primary motor cortex during postnatal development. Frontiers in Molecular Neuroscience 2021 14,754393. Impact factor: 5.64. Q1. Participating Groups: CO-05.
2. Hervás-Corpión I, Gallardo-Orihuela A, Catalina-Fernández I, Iglesias-Lozano I, Soto-Torres O, Geribaldi-Doldán N, Domínguez-García S, Luna-García N, Romero-García R, Mora-López F, Iriarte-Gahete M, Morales JC, Campos-Caro A, Castro C, Gil-Salú JL, Valor LM. Potential Diagnostic Value of the Differential Expression of Histone H3 Variants between Low- and High-Grade Gliomas. Cancers (Basel). 2021 ;13: Impact factor: 6.64. Q1. Participating Groups: CO-05, CO-02.
3. Matarredona ER, Zarco N, Castro C, and Guerrero-Cazares H. Editorial: Neural Stem Cells of the Subventricular Zone: From Neurogenesis to Glioblastoma Origin. Frontiers in Oncology 2021 Vol. 11 Issue 3719. Impact factor: 6.24. Q2. Participating Groups: CO-05.
4. Ezzanad, A; Gomez-Oliva, R; Escobar-Montaño, F; Diez-Salguero, M; Geribaldi-Doldan, N; Domínguez-García, S; Botubol-Ares, J; de los Reyes, C; Durán-Patrón, R; Nunez-Abades, P; Macías-Sánchez, A; Castro, C; Hernández-Galán, R. Phorbol diesters and 12-deoxy-16-hydroxyphorbol 13,16-diesters induce TGFα release and adult mouse neurogenesis. Journal of Medicinal Chemistry 64, 6070-6084. Impact factor: 6.8. First decile. Participating Groups: CO-05, IN48.
5. Geribaldi-Doldán, N.; Hervás-Corpión, I.; Gómez-Oliva, R.; Domínguez-García, S.; Ruiz, F.A.; Iglesias-Lozano, I.; Carrascal, L.; Pardillo-Díaz, R.; Gil-Salú, J.L.; Nunez-Abades, P.; Valor, L.M.; Castro, C*. Targeting Protein Kinase C in Glioblastoma Treatment. Biomedicines 2021, 9, 381. Impact factor: 6.081. Q1. Participating Groups: CO-05, IN48, IN12.
6. Gómez-Oliva R, Domínguez-García S, Carrascal L, Abalos-Martínez J, Pardillo-Díaz R, Verástegui C, Castro C, Nunez-Abades P, Geribaldi-Doldán N. Evolution of experimental models in the study of glioblastoma: toward finding efficient treatments. Frontiers in Oncology 2021, 10, 614295. Impact factor 6.24. Q2. Participating Groups: CO-05.
7. Domínguez-García S, Gómez-Oliva R, Geribaldi-Doldán N, Hierro-Bujalance C, Sendra M, Ruiz FA, Carrascal L, Macías-Sánchez AJ, Verástegui C, Hernández-Galán R, García-Alloza M, Nunez-Abades P, Castro C*. Effects of classical PKC activation on hippocampal neurogenesis and cognitive performance: mechanism of action. Neuropsychopharmacology. 2021 46, 1207-1219 doi 10.1038/s41386-020-00934-y.. Impact factor: 6.8. First decile. Participating Groups: CO-05, CO-18, IN48, IN12.
8. Delgado-Sequera, A, Hidalgo-Figueroa M, Barrera-Conde M , Duran-Ruiz MC, Castro C, Fernández-Avilés C, de la Torre R, Sánchez-Gomar I, Pérez V, Geribaldi-Doldán N, Robledo P and Berrocoso E. Olfactory Neuroepithelium Cells from Cannabis Users DisplAay Alterations to the Cytoskeleton and to Markers of Adhesion, Proliferation and Apoptosis. Molecular Neurobiology 2021 Apr;58(4):1695-1710. Impact factor 4.58. Q1. Participating Groups: CO-05, CO-09, CO-06.
9. The Role of Microglia in Glioblastoma. Geribaldi-Doldán N, Fernández-Ponce C, Quiroz RN, Sánchez-Gomar I, Escorcia LG, Velásquez EP, Quiroz EN. Front Oncol. 2021 Jan 29;10:603495. doi: 10.3389/fonc.2020.603495. eCollection 2020. Impact factor 6.24. Q2. Participating Groups: CO-05, CO-09, CO-10.
10. The Role of Glycosyltransferases in Colorectal Cancer. Fernández-Ponce C, Geribaldi-Doldán N, Sánchez-Gomar I, Quiroz RN, Ibarra LA, Escorcia LG, Fernández-Cisnal R, Martinez GA, García-Cózar F, Quiroz EN. Int J Mol Sci. 2021 May 30;22(11):5822. doi: 10.3390/ijms22115822. Impact factor 5.94. Q1. Participating Groups: CO-05, CO-09, CO-10.
11. Microalgae Aurantiochytrium Sp. Increases Neurogenesis and Improves Spatial Learning and Memory in Senescence-Accelerated Mouse-Prone 8 Mice. Sasaki K, Geribaldi-Doldán N, Wu Q, Davies J, Szele FG, Isoda H. Front Cell Dev Biol. 2021 Feb 9;8:600575. doi: 10.3389/fcell.2020.600575. Impact factor: 6.5. Q1. Participating Groups: CO-05.
12. Grape skin extract modulates neuronal stem cell proliferation and improves spatial learning in senescence-accelerated prone 8 mice. Sasaki K, Geribaldi-Doldan N, Szele FG, Isoda H. Aging (Albany NY). 2021 Jul 28;13(14):18131-18149. doi: 10.18632/aging.203373. Epub 2021 Jul 28. Impact factor: 5.5. Q1. Participating Groups: CO-05.

• Publications in collaboration with clinical-basic groups:
1. Hervás-Corpión I, Gallardo-Orihuela A, Catalina-Fernández I, Iglesias-Lozano I, Soto-Torres O, Geribaldi-Doldán N, Domínguez-García S, Luna-García N, Romero-García R, Mora-López F, Iriarte-Gahete M, Morales JC, Campos-Caro A, Castro C, Gil-Salú JL, Valor LM. Potential Diagnostic Value of the Differential Expression of Histone H3 Variants between Low- and High-Grade Gliomas. Cancers (Basel). 2021 ;13: Impact factor: 6.64. Q1. Participating Groups: CO-05, CO-02.
2. Matarredona ER, Zarco N, Castro C, and Guerrero-Cazares H. Editorial: Neural Stem Cells of the Subventricular Zone: From Neurogenesis to Glioblastoma Origin. Frontiers in Oncology 2021 Vol. 11 Issue 3719. Colaboración con grupo clínico de la Clínica Mayo. Impact factor: 6.24. Q2. Participating Groups: CO-05.
3. Geribaldi-Doldán, N.; Hervás-Corpión, I.; Gómez-Oliva, R.; Domínguez-García, S.; Ruiz, F.A.; Iglesias-Lozano, I.; Carrascal, L.; Pardillo-Díaz, R.; Gil-Salú, J.L.; Nunez-Abades, P.; Valor, L.M.; Castro, C*. Targeting Protein Kinase C in Glioblastoma Treatment. Biomedicines 2021, 9, 381. Impact factor: 6.081. Q1. Participating Groups: CO-05, IN48, IN12.

1. Eugenia Flores-Giubi, Noelia Geribaldi-Doldán, Maribel Murillo-Carretero, Carmen Castro,* Rosa Durán-Patrón, Antonio J. Macías-Sánchez*, Rosario Hernández-Galán Lathyrane, premyrsinane and related diterpenesfrom Euphorbia boetica Boiss: effect on in vitro Tratamos la información que nos facilita con el fin de prestarles el servicio solicitado. Los datos proporcionados se conservarán hasta que el interesado no solicite su supresión; de esta manera estos datos se publicarán en la web del INIBICA con el fin de dar cumplimiento del principio de transparencia publicación. neural progenitor cell proliferation (* Corresponding authors). Journal of Natural Products. 2019. In press. Impact factor : 4.25 1st Decile.
2. Geribaldi-Doldán N., Gómez-Oliva R., Domínguez García S., Núnez-Abades P., and Castro C* Protein Kinase C: targets to regenerate brain injuries?. Frontiers in Cell and Developmental Biology.2019. 7, 39- Impact factor 5.20 1st Quartile
3. Domínguez-García S, Castro C* and Geribaldi-Doldán N*. ADAM17/TACE a key molecule in brain injury regeneration. Neural Regen Res 2019, 14, 1378-79. Impact factor: 2.7 3rd quartile.

1. García-Bernal F, Geribaldi-Doldán N, Domínguez García, S., Díez-Salguero M., Carrasco M, MurilloCarretero M, Verástegui C, y Castro C*. Protein kinase C inhibition promotes neurogenesis in brain injuries Frontiers in Cellular Neuroscience 2018, 2018 Nov 27;12:462 Impact factor: 3.9 2nd quartile.
2. Geribaldi-Doldán N, Carrasco M, Murillo-Carretero M, Domínguez-García S, García-Cózar F, MuñozMiranda JP, Del Río-García V, Verástegui C, Castro C*. Specific inhibition of ADAM17/TACE promotes neurogenesis in the injured motor cortex. Cell Death Dis. 28;9(9):862 2018. Impact factor: 5.9 1st Quartile.

1. Murillo-Carretero M, Geribaldi-Doldán N, FloresGiubi E, García-Bernal F, Navarro-Quiroz EA, Carrasco M, Macías-Sánchez AJ, HerreroFoncubierta P, Delgado-Ariza A, Verástegui C, Domínguez-Riscart J, Daoubi M, Hernández-Galán R, Castro C*. ELAC (3,12-di-O-acetyl-8-O-tigloilingol), a plant-derived lathyrane diterpene, induces subventricular zone neural progenitor cell proliferation through PKCβ activation. Br J Pharmacol. 2017 May 5. doi: 10.1111/bph.13846. Impact factor: 6.8 1st Decile.

1. Rabaneda LG, Geribaldi-Doldán N, Murillo-Carretero M, Carrasco M, Martínez-Salas JM, Verástegui C, Castro C*. Altered regulation of the Spry2/Dyrk1A/PP2A triad by homocysteine impairs neural progenitor cell proliferation. Biochim Biophys Acta. 2016 Dec;1863(12):3015-3026. Impact factor 4.52 1st Quartile.

1. Geribaldi-Doldán N, Flores-Giubi E, Murillo-Carretero M, García-Bernal FJ, Macías-Sánchez AJ, Carrasco M, Domínguez-Riscart J, Verástegui C, Hernández.-Galán R, and Castro C*. “12-Deoxiphorbols promote adult neurogenesis by inducing neural progenitor cell proliferation via PKC activation”. Int J Neuropsychopharmacol. 2015 19 (1). Impact factor: 4.72 1st Quartile.

1. Carrasco M, Rabaneda L.G., Ortega-Martínez S., Tratamos la información que nos facilita con el fin de prestarles el servicio solicitado. Los datos proporcionados se conservarán hasta que el interesado no solicite su supresión; de esta manera estos datos se publicarán en la web del INIBICA con el fin de dar cumplimiento del principio de transparencia Murillo-Carretero M, Martinez-Chantar ML, Woodhoo A, Luka Z, Wagner C, Mato JM, Micó JA, and Castro C*. Glycine N-methyltransferase expression in mouse hippocampus and its role in neurogénesis and cognitive performance. 2014; Hippocampus 24 840-852. Impact factor: 5.49 1st Quartile.
2. García-Bueno B, Bioque M, Mac-Dowell KS, Barcones MF, Martínez-Cengotitabengoa M, PinaCamacho L, Rodríguez-Jiménez R, Sáiz PA, Castro C, Lafuente A, Santabárbara J, González-Pinto A, Parellada M, Rubio G, García-Portilla MP, Micó JA, Bernardo M, Leza JC. Pro-/Anti-inflammatory Dysregulation in Patients With First Episode of Psychosis:Toward an Integrative Inflammatory Hypothesis of Schizophrenia. Schizophr Bull. 2014 Mar;40(2):376-87. Impact factor 8.8 1st Decile.

• AUTHORS: Castro C Hernández-Galán R, Macías-Sánchez AJ, Geribaldi-Doldán N, Durán Patrón R, Gómez-Oliva R, Domínguez-García S, Botubol-Ares M, Escobar-Montaño F, Ezzanad A, Nunez-Abades P. TITLE: Derivados de 12-desoxiforboles y uso de los mismos. REQUEST NUMBER: P202031132. PRIORITY DATE: 29-12-2020. OWNER ENTITY: University of Cadiz. COUNTRIES OF APPLICATION: Spain. SITUATION: REQUESTED/INTERNATIONAL EXTENSION/EXPIRED: Extensión PCT.