FP6 priority

1.1.1   Genomics and Biotechnology for Health

1.2.

Title of the proposal

The role of NO/cGMP signaling pathway in neurodegenerative disorders: ischemia-reperfusion, trauma

Institute

Slovak Academy of Sciences, Institute of Neurobiology
Soltesovej 4, 040 01 Kosice, Slovak Republic

Contact

Research subject for a potential FP6 project

Spinal cord injury produces an enormous metabolic stress and, if not directly lethal, may cause deep changes resulting in irreversible loss of neurologic function leading to spastic or flaccid paraplegia. To date, a coherent information regarding the NO-cGMP signaling pathway is only for those parts of the CNS having a well-defined synaptic circuitry. However, limited data are available for the white matter composed of glial cells, axons and entirely devoid of synapses. The mechanism of ischemia/reperfusion and traumatic injury of the spinal cord will be monitored by nitric oxide synthase activity and cGMP level in the white matter columns. Both parameters reflecting the spinal cord injury in the extent of lumbosacral enlargements will be compared with the ensuing changes occurring in the gray matter regions. The extent of damage will be complemented with regard to the localization of NOS-IR and NADPH diaphorase neuronal and axonal pools. Neuroprotective effect of drugs influencing the NOS activity and cGMP level will be studied and compared with the motor function of hind limbs.

Recent international cooperation of the research team

Prof. J. Strosznajder, Department of Cellular Signalling, Centre of Experimental and Clinical medicine, Polish Academy of Science, Warsaw, Poland

Proposer´s relevant publications related to the research subject

Lukacova, N., Cizkova, D., Marsala, M., Jalc, P., Marsala, J. Segmental and laminar distribution of NADPH diaphorase exhibiting and neuronal nitric oxide synthase immunoreactive neurons versus radioassay detection of catalytic nitric oxide synthase activity in the spinal cord of rabbit, Neuroscience, 94:229-237, 1999.
Lukacova N, Cizkova D, Marsala M, Pavel J, Jalc P, Sulla I, Kafka J, Marsala J. Effect of midthoracic spinal cord constriction on catalytic nitric oxide synthase activity in the white matter columns of rabbit. Neurochem Res. 2000 25(8):1139-48.
Lukacova N., Pavel J., Jalc P., Cizkova D., Marsala M., Lukac I., Chalimoniuk M., Strosznajder J. Marsala J. Effect of spinal cord compression on cyclic 3’,5’-guanosine monophosphate in the white matter columns of rabbit. Neurochem. Int. 2001, 39:275-282.
Pavel, J., Lukacova, N., Marsala, J., Marsala M. The regional changes of NOS activity in the spinal cord of the rabbit after repeated sublethal ischemia. Neurochem. Res. 2001, 26:831-837.
Lukacova N., Cizkova D., Marsala M., Lukac I., Marsala J. The regional distribution of nitric oxide synthase activity in the spinal cord of the dog. Brain Res. Bull. 2002 (in press).