Cabecera CBMSO CSIC UAM

Thursday, 5th December 2019

2015.5.8.mkokaia

 

Prof. Merab Kokaia

Epilepsy Center, Department of Clinical Sciences

Lund University Hospital, Sweden

 

 

 

 

 

2015 04 24 merab kokaia minEl genoma está regulado en múltiples niveles, y las células necesitan integrar las señales externas e internas y coordinar los diferentes niveles de regulación para ejercer adecuadamente las funciones biológicas. El flujo de información a partir de un determinado genoma (genotipo) y el medio ambiente para producir el fenotipo resultante, está mediado por el “transcriptoma”, con la contribución general, y aún desconocida, de numerosos ARN no codificantes.

El laboratorio del Prof. Kokaia explora el papel de neuropéptidos y factores neurotróficos modulando la transmisión sináptica excitatoria e inhibitoria y la epileptogénesis en cerebro. Para ello utilizan ratas y ratones transgénicos, en combinación con el uso de modelos experimentales de Epilepsia in vivo (kindling, status epilepticus) y abordajes in vitro (patch-clamp en rodajas de cerebro, optogenética). Unos de los objetivos principales de la investigación consiste en el uso de transferencia génica directa e indirecta hacia dianas concretas de neuropéptidos y factores neurotróficos en diferentes regiones cerebrales, para investigar los aspectos mecanísticos de su acción a nivel de transmisión sináptica y epileptogénesis. Su grupo también explora los efectos anticonvulsivos del abordaje mediante manipulación optogenética in vitro e in vivo en modelos animales de Epilepsia.

Los resultados de esta investigación ayudarán a entender mejor los mecanismos de epileptogénesis y podrían en un futuro dar lugar al desarrollo de nuevas estrategias basadas en terapia génica para el tratamiento de la Epilepsia.

(Más información: Dr. Alberto Martínez Serrano, This email address is being protected from spambots. You need JavaScript enabled to view it.)

 


 

Epilepsy is one of the most devastating neurological diseases affecting about 1% of the population of the western countries. Despite certain progress in antiepileptic drug development in about 30-40% of cases epileptic seizures do not respond to conventional pharmacological treatment therapies. Recently neuropeptides and neurotrophic factors emerged as strong regulators of excitatory and inhibitory synaptic transmission in the CNS thus offering a potent tool to counteract the seizure activity. However, it is not clear what the role of these agents is in mechanisms of epileptogenesis.

Kokaia’s lab explores the role of neuropeptides and neurotrophic factors in modulation of excitatory and inhibitory synaptic transmission and epileptogensis in the brain. We use rats and traNSgenic mice in combination with in vivo epilepsy models (Kindling, status epilepsitcus) and in vitro approaches (patch-clamp in brain slices, optogenetics). One of the specific aims of this research line is to use both direct and indirect targeted gene transfer of neuropeptides and neurotrophic factors into the different brain regions to investigate mechanistic aspects of their action on synaptic transmission and epileptogensis. The group also explores seizure-suppressant effects of optogenetic approach in vitro and in vivo in animal models of epilepsy.

This research will help in better understanding of the mechanisms for epileptogenesis and might lead to development of new gene therapy-based strategies for epilepsy treatment.

(More information: Dr. Alberto Martínez Serrano, This email address is being protected from spambots. You need JavaScript enabled to view it.)

 

Publicaciones seleccionadas / Selected publications:

  • Ritter et al. (2014) Epilepsia, 55, 1693
  • Avaliani et al (2014) Stem Cells, 32, 3088
  • Krook‐Magnuson et al (2014) Ad. Exp. Med. Biol., 813, 319
  • Ledri et al (2014) J. Neurosci., 34, 3364
  • Galanopoulou et al (2013) Epilepsia 54: 13
  • Galanopoulou et al (2012) Epilepsia 53, 571

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