Research

Area 4

Neurobiology unit

Team manager
Ramon Trullàs
(IIBB-CSIC)

Strategic objectives

To investigate molecular mechanisms of excitotoxic neuron death and apoptotic death with the aim of identifying new therapeutic-intervention targets for the treatment of neurodegenerative diseases. Another objective is to understand the mechanisms that regulate neurogenesis in the adult brain in experimental models and in human neurodegenerative diseases.

Main lines of research

1. Investigation of the biochemical mechanisms that produce excitotoxic neuron death. This project posits that inhibition of phospholipid synthesis is a key mechanism in neuron death caused by over-activation of glutamatergic receptors.

2. Investigation of the function of neuronal pentraxin 1 during programmed neuronal death with the hypothesis that inhibiting the expression of this gene may provide a new treatment for chronic neurodegenerative disorders.

3. Study of the mechanism by which the KATP channel modifies microglial activation and thereby characterize in vitro and in vivo the neuroprotector and neurotoxic effect of microglia in situations of brain damage by activation and blocking of this channel.

4. Investigation of the role of the glia in mechanisms of neurogenesis associated with chronic neurodegeneration in the adult brain hippocampus.

5. Investigation of the efficacy and safety of anti-Abeta immune therapy as a treatment for Alzheimer disease.

We have shown that excitotoxic hippocampal damage induces the migration of neuroblasts from the subventricular region to the injured hippocampus, thereby generating neurogenesis independent of that of the hippocampus itself. Also, in certain conditions of excitotoxicity, we have shown that the microglia may present neuroprotective activity and that this activity can be controlled by means of the activity of the KATP channels.

In studies carried out in primary cultures of cortical neurons, we have also shown that the reduction of the expression of neuronal pentraxin 1 by interference with its RNA causes a very marked increase in the number of excitor synapses. Furthermore, in studies carried out in models of Alzheimer disease, we have confirmed that neuronal pentraxin 1 causes loss of synapses, damage to neurites and apoptotic neurotoxicity. These results indicate that reducing the quantity of neuronal pentraxin 1 may impede the reduction in synaptic contacts that occurs in Alzheimer disease.