Molecular basis of glutamatergic synapses

Research summary:

The work of our laboratory is dedicated to the understanding of the molecular and cellular mechanisms of neuroprotection and neuroregeneration of the brain against injuries such as cerebral ischemia. For us, the characterization of the neuroreparative mechanisms activated during the so-called ischemic tolerance is of special interest. These mechanisms are induced in response to moderate brain lesions and make this organ resistant to more severe damage that may subsequently suffer. These plastic responses of the brain involve mechanisms ranging from modifications in the activity of the glutamatergic pathways (main executors of toxic damage), to the activation of antioxidant mechanisms and, probably, the generation of new cells through neurogenesis. In relation to glutamatergic pathways, we have investigated the role of glutamate transporters and the potential cross talk with other pathways (like glycinergic and dopaminergic). We have found that the potassium channels regulate the activity of glutamate and dopamine transporters under different circumstances. Moreover, we have found that some microRNAs produced by neurons (mir-96 and mir-137) might impact on the activity of the glycine transporter GLYT1, present in glial cells. We are investigating how these and other microRNAs are packaged into exosomes and are transferred between neurons and glia and vice versa, as neuroprotective agents.  Relative to the neurogenic response, we are interested first, in the basic mechanisms by which this process is activated in the adult brain, and second, how this can be modified is a response to situations of stress. In particular, Eva Porlan's group main focus is the potential of druggable targets for enhancing adult neural stem proliferation and neurogenic output with focus in two experimental paradigms: regeneration of the adult supependymal zone after depletion of progeny, and hipoxia. Dr. Porlan’s leading interest is the elucidation of the mechanisms underlying the maintenance of the adult neural stem and progenitor cell pools, their implications in pathological conditions and their potential for regenerative processes and therapeutic interventions.

During this time, we have maintained collaborations with the groups of Dr. F.J. Díez-Guerra, in exosome transfer and imaging studies, Drs. B. López-Corcuera (CBM) and C. Avendaño (UAM) on the role of glycinergic pathways, Dr. A. Rodríguez Artalejo (UCM) and D. Bartolomé-Martín in the study of the activity of the sodium and potassium channels. Also with Dr. I. Fariñas (UV, CIBERNED), Dr. M. Malumbres (CNIO) and Dr. T. Iglesias (IIBM Alberto Sols, CSIC) for the adult neurogenesis studies.

 

Image

Figure 1. Mouse neurospheres from the adult subependymal neurogenic niche stained with nestin (red) and DAPI (blue).

Image


* For external calls please dial 34 91196 followed by the extension number
Last nameNameLaboratoryExt.*e-mailProfessional category
Maestre GuillénAlejandro3064655Estudiante TFM
Núñez BalbuenaEnrique3044656enunez(at)cbm.csic.esE. Técnicos Superiores Especializados de Organismos Públicos de Investigación
Zafra GómezFrancisco3064630fzafra(at)cbm.csic.esCatedrático Universidad, GA

Relevant publications:

  • Bartolomé-Martín, D., Ibáñez, I., Piniella, D., Martínez-Blanco, E., Pelaz, S.G. and Zafra, F. (2019) Identification of potassium channel proteins Kv7.2/7.3 as common partners of the dopamine and glutamate transporters DAT and GLT-1. Neuropharmacology 161,107568. doi: 10.1016/j.neuropharm.2019.03.011
  • Morante-Redolat, J.M., Porlan, E. (2019) Neural Stem Cell Regulation by Adhesion Molecules Within the Subependymal Niche. Front Cell Dev Biol. 7, 102. doi: 10.3389/fcell.2019.00102.
  • Zafra, F.*, Aragón, C., Olivares, L., Danbolt, N.C, Giménez, C., Storm-Mathisen, J. (1995) "Glycine transporters are differentially expressed among CNS cells". J. Neurosci. 15, 3952-3969. IF7.5 Number of citations: 289
  • Casado, M., Bendahan, A., Zafra, F., Danbolt, N.C., Aragón, C., Giménez, C. Kanner, B.I.* (1993) "Phosphorylation and modulation of brain glutamate transporters by protein kinase C". J. Biol. Chem. 268, 27313-27317. IF5.6 Number of citations: 242
  • Zafra, F., Gomeza, J., Olivares, L., Aragón, C., Giménez. C.* (1995) "Regional distribution and developmental changes of glycine transporters (GLYT1 and GLYT2) in rat brain". Eur. J. Neurosci. 7, 1342-1352. IF3.7 Number of citations: 149
  • Cubelos, B., Giménez, C., Zafra F.* (2005) Localization at glutamatergic synapses of the glycine transporter GLYT1. Cerebral Cortex 15(4):448-459. IF6.5 Number of citations: 111
  • Casado, M., Zafra, F., Aragón, M.C., Giménez, C.* (1990) "Activation of high-affinity uptake of glutamate by phorbol esters in primary glial cell cultures." J. Neurochem. 57, 1185-1190. IF4.6 Number of citations: 98
  • Zafra, F., Hengerer, B., Leibrock, J., Thoenen, H., Lindholm,D. (1990) "Activity dependent regulation of BDNF and NGF mRNAs in the rat hippocampus is mediated by non-NMDA glutamate receptors." EMBO. J. 9, 3545-3550. IF8.7 Number of citations: 723
  • Zafra, F., Castrén, E., Thoenen, H., Lindholm, D. (1991) "Interplay between glutamate and γ-aminobutyric acid transmitter systems in the physiological regulation of brain-derived neurotrophic factor and nerve growth factor synthesis in hippocampal neurons." Proc. Natl. Acad. Sci. USA 88, 10037-10041. IF9.6 Number of citations: 424

NOTE! This site uses cookies and similar technologies.

If you not change browser settings, you agree to it. Learn more

I understand

COOKIES POLICY

What are cookies?

A cookie is a file that is downloaded to your computer when you access certain web pages. Cookies allow a web page, among other things, to store and retrieve information about the browsing habits of a user or their equipment and, depending on the information they contain and the way they use their equipment, they can be used to recognize the user.

Types of cookies

Classification of cookies is made according to a series of categories. However, it is necessary to take into account that the same cookie can be included in more than one category.

  1. Cookies according to the entity that manages them

    Depending on the entity that manages the computer or domain from which the cookies are sent and treat the data obtained, we can distinguish:

    • Own cookies: those that are sent to the user's terminal equipment from a computer or domain managed by the editor itself and from which the service requested by the user is provided.
    • Third party cookies: those that are sent to the user's terminal equipment from a computer or domain that is not managed by the publisher, but by another entity that processes the data obtained through the cookies. When cookies are installed from a computer or domain managed by the publisher itself, but the information collected through them is managed by a third party, they cannot be considered as own cookies.

  2. Cookies according to the period of time they remain activated

    Depending on the length of time that they remain activated in the terminal equipment, we can distinguish:

    • Session cookies: type of cookies designed to collect and store data while the user accesses a web page. They are usually used to store information that only is kept to provide the service requested by the user on a single occasion (e.g. a list of products purchased).
    • Persistent cookies: type of cookies in which the data is still stored in the terminal and can be accessed and processed during a period defined by the person responsible for the cookie, which can range from a few minutes to several years.

  3. Cookies according to their purpose

    Depending on the purpose for which the data obtained through cookies are processed, we can distinguish between:

    • Technical cookies: those that allow the user to navigate through a web page, platform or application and the use of different options or services that exist in it, such as controlling traffic and data communication, identifying the session, access to restricted access parts, remember the elements that make up an order, perform the purchase process of an order, make a registration or participation in an event, use security elements during navigation, store content for the broadcast videos or sound or share content through social networks.
    • Personalization cookies: those that allow the user to access the service with some predefined general characteristics based on a series of criteria in the user's terminal, such as the language, the type of browser through which the user accesses the service, the regional configuration from where you access the service, etc.
    • Analytical cookies: those that allow the person responsible for them to monitor and analyse the behaviour of the users of the websites to which they are linked. The information collected through this type of cookies is used in the measurement of the activity of the websites, applications or platforms, and for the elaboration of navigation profiles of the users of said sites, applications and platforms, in order to introduce improvements in the analysis of the data of use made by the users of the service.

Cookies used on our website

The CBMSO website uses Google Analytics. Google Analytics is a simple and easy to use tool that helps website owners to measure how users interact with the content of the site. You can consult more information about the cookies used by Google Analitycs in this link.

Acceptance of the Cookies Policy

The CBMSO assumes that you accept the use of cookies if you continue browsing, considering that it is a conscious and positive action from which the user's consent is inferred. In this regard, you are previously informed that such behaviour will be interpreted that you accept the installation and use of cookies.

Knowing this information, it is possible to carry out the following actions:

  • Accept cookies: if the user presses the acceptance button, this warning will not be displayed again when accessing any page of the portal.
  • Review the cookies policy: the user can access to this page in which the use of cookies is detailed, as well as links to modify the browser settings.

How to modify the configuration of cookies

Using your browser you can restrict, block or delete cookies from any web page. In each browser the process is different, here we show you links on this particular of the most used browsers: