Research

Area 4

Neurobiology Unit

Team leader

  • Ramon Trullàs
    (IIBB-CSIC)

Strategic objectives

The Neurobiology Unit investigates molecular mechanisms of excitotoxic and apoptotic neuron death with the objective of identifying new therapeutic targets for the management of neurodegenerative diseases. Another objective is to gain knowledge of the mechanisms regulating neurogenesis in the adult brain.

Main lines of research
  1. Investigation of the biochemical mechanisms causing excitotoxic neuron death. This project postulates that the inhibition of phospholipid synthesis is a key mechanism in neuron death produced by over-activation of glutamatergic receptors.
  2. Investigation of the function of neuronal pentraxin 1 (NP1) during programmed neuron death, with the hypothesis that inhibition of the expression of this protein may constitute a new treatment for chronic neurodegenerative disorders.
  3. Study of the mechanism by which the KATP channel modulates microglial activation, thereby allowing the in vivo and in vitro characterization of the neuroprotective and neurotoxic effect of microglia in situations of brain damage, through the activation and blockade of this channel.
  4. Investigation of the role of the glia in the neurogenesis mechanisms associated with chronic neurodegeneration in the hippocampus of the adult brain.
  5. Investigation of the efficacy and safety of anti-A beta immunotherapy as treatment for Alzheimer’s disease.

We have shown that shortly after activation of the apoptotic death program, NP1 synthesis begins and is directed towards the mitochondria, where the protein facilitates Bax activation. Blocking the synthesis of NP1 prevents Bax activation and arrests the apoptotic death process. We have also shown that excitotoxic hippocampal damage induces a chronic neurodegenerative process with the migration of neuroblasts from the subventricular zone towards the damaged hippocampus – this inducing neurogenesis independent of that intrinsic to the actual hippocampus. Likewise, in the early stages of excitotoxic damage, the microglia undergoes a change in phenotype, evolving from neuroprotective activity towards a more proinflammatory profile. Under these conditions, we have shown that activation of the microglial KATP channels reduces this proinflammatory activity and reduces neuronal damage.