Avaluació del tractament amb liti com a citoprotector, gliostàtic i neuroplàstic: estudis in vitro i in vivo després de lesió traumàtica del còrtex cerebral en rates

  • Claro Izaguirre, Enrique (Principal Investigator)
  • Avouambet, William Sabin (Scholar)
  • García Andreolotti, Alberto (Scholar)
  • Picatoste Ramón, Fernando (Investigator)

Project Details

Description

Our own previous work has shown that lithium treatment of neural cells in culture results in: 1) the stimulation of the MEK-ERK signalling cascade in neurons, where it serves survival and plastic functions; 2) the inhibition of the same MEK-ERK pathway in astrocytes, where it is implicated in cell proliferation; 3) the general cytoprotection of both neurons and astrocytes against a variety of apoptotic insults, and 4) the stimulation of CTP: phosphocholine cytidylytransferase (CCT), which is the rate-limiting step in phosphatidylcholine synthesis, and whose inhibition induces cell death. On this background, our general hypothesis considers that lithium treatment, which has been widely used for decades in the therapy of bipolar disorders, should be effective to favour neutral repair after traumatic brain injury, a situation where the reestablishment of neuronal connexions is known to be hampered by reactive gliosis and glial scaring. Therefore, the specific aims of this grant proposal are as follows: 1) to determine the molecular mechanism/s whereby lithium stimulates phosphatidylcholine synthesis in neurons and astrocytes; 2) to test experimentally the feasibility of a model of reactive astrogliosis in vitro and, subsequently, to verify whether lithium inhibits reactive astrogliosis, and 3) to determine in a rat model of traumatic injury of the cerebral cortex, which induces thalamic neurodegeneration, wether lithium treatment is effective to confer cytoprotection, favours neuronal regeneration, and inhibits reactive gliosis and glial scaring.
StatusFinished
Effective start/end date29/11/0328/11/06

Funding

  • Instituto de Salud "Carlos III": €38,755.00

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