CENTRO DE BIOLOGÍA MOLECULAR SEVERO OCHOA

Adult neurogenesis and neurodegenerative diseases

Research summary:

Our research group investigates the mechanisms that control adult hippocampal neurogenesis, both under physiological and pathological conditions. We perform in vivo and in vitro studies animal models of different diseases, and also use human brain samples. In particular, we are interested in determining the therapeutic potential of increasing adult hippocampal neurogenesis for the treatment of neurodegenerative diseases such as Alzheimer´s disease (AD) and other tauopathies, and psychiatric ilnesses. The hippocampus is one of the most affected areas in these diseases. This brain region plays a crucial role in learning and memory. Furthermore, a unique feature of this structure is the existence of adult neurogenesis. The process of adult hippocampal neurogenesis encompasses the birth and functional integration of newborn neurons throughout lifetime. Adult hippocampal circuit confers and extraordinary degree of plasticity to the circuit. Thus, we work to develop strategies capable of increasing the functionality of newborn neurons.

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Image of the human dentate gyrus showing immature (in red) and mature (blue) neurons in the hippocampal granule cell layer. Credits: LlorensLab.

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* For external calls please dial 34 91196 followed by the extension number
Last nameNameLaboratoryExt.*e-mailProfessional category
Flor GarcíaMiguel de la2134533miguel.delaflor(at)cbm.csic.esTit.Sup.Activ.Técn.y Profes. GP1
Llorens MartínMaría Victoria2134632mllorens(at)cbm.csic.esInvestigador
Márquez ValadezBerenice2134533Becario Erasmus
Moreno JiménezElena2134533elena.moreno(at)cbm.csic.esAyudante Investigación
Rodríguez MorenoCarla2134533carla.rodriguez(at)cbm.csic.esContratado CIBER
Terreros RoncalJulia2134533j.terrerosr(at)cbm.csic.esTitulado Sup.de Actividades Técn. y Profes. GP1

Relevant publications:

  • Unraveling human adult hippocampal neurogenesis. Flor-García M*; Terreros-Roncal J*; Moreno-Jiménez E.P*; Ávila J; Rábano A; Llorens-Martín M. Nature Protocols, In press.
  • Adult hippocampal neurogenesis is abundant in neurologically healthy subjects and drops sharply in Alzheimer´s disease patients. Moreno-Jiménez E.P; Flor-García M; Terreros-Roncal J; Rábano A, Cafini F, Pallas-Bazarra N, Ávila J, Llorens-Martín M. Nature Medicine. 2019 Apr, 25(4):554-60. PMID: 30911133.
  • Circuits of mature and immature neurons in the hippocampus. Llorens-Martín M. SCIENCE. 2019 May 10;364(6440):530.
  • Activity-dependent reconnection of adult-born dentate granule cells in a mouse model of frontotemporal dementia. Terreros-Roncal J; Flor-García M*; Moreno-Jiménez EP*; Pallas-Bazarra N*; Rábano A; Sah N; van Praag H; Giacomini D; Schinder AF; Ávila J; Llorens-Martín M. The Journal of Neuroscience. 2019 Jul 17;39(29):5794-5815.
  • Maturation dynamics of the axon initial segment (AIS) of newborn dentate granule cells in young adult C57BL/6J mice. Bolós M, Terreros-Roncal J, Perea JR, Pallas-Bazarra N, Ávila J, Llorens-Martín M. The Journal of Neuroscience. 2019 Jan 16. pii: 2253-18. PMID: 30651327.
  • Soluble Tau has devastating effects on the structural plasticity of hippocampal granule neurons. Bolós M; Pallas-Bazarra N; Terreros-Roncal J; Perea JR; Jurado-Arjona J, Ávila J; Llorens-Martín M. Translational Psychiatry.
  • Absence of microglial CX3CR1 impairs the synaptic integration of adult-born hippocampal granule neurons. Bolós M; Perea JR; Terreros-Roncal J; Pallas-Bazarra N; Jurado-Arjona J, Ávila J; Llorens-Martín M. Brain Behav Immun. 2017 Oct 7. pii: S0889-1591(17)30455-5.
  • GSK-3β overexpression alters the dendritic spines of developmentally generated granule neurons in the mouse hippocampal dentate gyrus. Pallas-Bazarra N, Kastanauskaite A, Avila J, DeFelipe J, Llorens-Martín M. Frontiers in Neuroanatomy. 2017 Mar 10;11:18.
  • Novel function of Tau in regulating the effects of external stimuli on adult hippocampal neurogenesis. Pallas-Bazarra N, Jurado-Arjona J, Navarrete M, Esteban JA, Hernández F, Ávila J, Llorens-Martín M. EMBO J. 2016 Jul 1; 35 (13) :1417 - 36.
  • Versatile use of rtTA-expressing retroviruses in the study of neurodegeneration. Teixeira CM, Ávila J, Llorens-Martín M. Oncotarget. 2016 Dec 30. doi: 10.18632/oncotarget.14386.
  • Llorens-Martín M, Fuster-Matanzo A, Teixeira CM, Jurado-Arjona J, Ulloa F, Defelipe J, Rábano A, Hernández F, Soriano E, Avila J. GSK-3β overexpression causes reversible alterations on postsynaptic densities and dendritic morphology of hippocampal granule neurons in vivo. Mol Psychiatry. 2013 Apr;18(4):451-60.

Doctoral theses and Master Final dissertation projects:

  • Noemí Pallas Bazarra. “Study of the role of Tau protein on the modulation of adult hippocampal neurogenesis”. Universidad Autónoma de Madrid. July-2015. Calificación: Mark Summa Cum Laude. CBMSO PINP Award 2017.
  • Miguel de la Flor García. Master´s final dissertation: “Novel retroviral tools to express toxic proteins in newborn granule neurons”. Universidad Autónoma de Madrid. September 2018.
  • Héctor Cañeque Rufo. Degree´s final dissertation: “Chemoactivation potential to restore de functionality of newborn granule neurons in a mouse model of Tauopathy”. Universidad Autónoma de Madrid. June 2019.

Current supervision of Ph.D. and M.Sc. Projects:

  • Julia Terreros-Roncal (Ph.D. student Universidad Autónoma de Madrid)
  • Elena Moreno Jiménez (Ph.D. student Universidad Autónoma de Madrid)
  • Miguel de la Flor García (Ph.D. student Universidad Autónoma de Madrid)
  • Héctor Cañeque Rufo (M.Sc. student Universidad Autónoma de Madrid)

Funding:

  • The Alzheimer´s Association (New Investigator Research Grant 2015-2017)
  • The Alzheimer´s Association (Alzheimer Association Research Grant 2018-2020)
  • The Association for Frontotemporal Dementia (Basic Science Pilot Grant Award 2016-2017)
  • Spanish Ministry of Economy and Competitiveness (Ramón y Cajal contract, 2017-2021)
  • Spanish Ministry of Economy and Competitiveness (Programa Estatal I+D+i orientada a los retos de la sociedad, 2018-2020)
  • Comunidad de Madrid, Programa de Garantía de Empleo Juvenil (2018-2019)

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