Wednesday, 20th June 2018

Molecular Neuropathology

Adult neurogenesis and neurodegenerative diseases

 


Grupo-400

 


María Llorens-Martín


DSciStaff

 

 

DPublications

 

Research summary:

Our research group is focused on investigating the mechanisms that control adult hippocampal neurogenesis, both under physiological and pathological conditions. 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. These diseases are characterized by a general loss of neural plasticity. In this regard, one of most affected areas is the hippocampus. 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. This process confers and extraordinary high level of plasticity to the hippocampus. Thus, numerous strategies aim to potentiate the functionality of these newborn neurons and to counteract the loss of neural plasticity are being currently developed. We aim to understand the cellular mechanisms driving the impairment in the functional integration of newborn neurons that takes place in the brain of AD patients by using several animal models of the disease. Moreover, we are trying to find neuroprotective strategies that may prevent and/or slow down the advance of this devastating disease.

 

fig1









In this picture, two newborn granule neurons are shown. In red, it can be visualized the green fluorescent protein (GFP) labeling the whole dendritic structure of the newborn granule neurons. In green, the postsynaptic densities of these newborn granule neurons can be observed.

 

 


 

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)

 


 

Doctoral theses:

  • Noemí Pallas Bazarra. “Study of the role of Tau protein on the modulation of adult hippocampal neurogenesis”. Universidad Autónoma de Madrid. July-2015. Mark: Summa Cum Laude. CBMSO PINP Award 2017

 


 

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 (M.Sc. student Universidad Autónoma de Madrid)

 


 

Selected Publications:

  • 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.