The activation of ERK1/2 and p38 mitogen-activated protein kinases is dynamically regulated in the developing rat...

Mitogen-activated protein kinases (MAPKs) are serine/threonine kinases that play an instrumental role in signal transduction from the cell surface to the nucleus. These enzymes are major intracellular mediators of developmental events and recently have been shown to control also synaptic plasticity processes [Sweatt, J.D., 2004. Mitogen-activated protein kinases in synaptic plasticity and memory. Curr. Opin. Neurobiol. 14, 311-317; Thomas, G.M., Huganir, R.L., 2004. MAPK cascade signalling and synaptic plasticity. Nat. Rev. Neurosci. 5, 173-183]. Mammalian members of this family are extracellular signal-regulated kinases 1/2 (ERK 1/2), c-Jun amino-terminal kinases or stress-activated protein kinases (JNK/SAPKs) and p38 kinases (p38(MAPK)). At the level of the visual system, it has been demonstrated that the ERK pathway regulates developmental plastic processes at both retino-thalamic and thalamo-cortical level and that p38(MAPK) controls a peculiar form of long-term depression in the visual cortex [Di Cristo, G., Berardi, N., Cancedda, L., Pizzorusso, T., Putignano, E., Ratto, G.M., Maffei, L., 2001. Requirement of ERK activation for visual cortical plasticity. Science 292, 2337-2340; Naska, S., Cenni, M.C., Menna, E., Maffei, L., 2004. ERK signaling is required for eye-specific retino-geniculate segregation. Development 131, 3559-3570; Xiong, W., Kojic, L.Z., Zhang, L., Prasad, S.S., Douglas, R., Wang, Y., Cynader, M.S., 2006. Anisomycin activates p38 MAP kinase to induce LTD in mouse primary visual cortex. Brain Res. 1085, 68-76]. Here, as a first approach to gain more insight on the role of two MAPKs - ERK1/2 and p38(MAPK) - in visual system maturation, we characterized by western blot the regulation of their phosphorylation/activation in rat retina, superior colliculus and visual cortex, during postnatal development from birth to adult age. Our main results show that: (i) in the retina p38(MAPK) activation peaks at P4, and then, from P15 to P45, both ERK1/2 and p38(MAPK) phosphorylation increases; (ii) in the superior colliculus phosphorylation of both MAPKs increases between P4 and P15; (iii) in the visual cortex ERK1/2 phosphorylation increases from P15 to P45, while phosphorylation of p38(MAPK) increases starting from P4. The present data demonstrate a distinct regulation of the activation of ERK1/2 and p38(MAPK) in the three visual areas analyzed which occurs in temporal correlation with critical events for visual system maturation. These results suggest an important role for ERK1/2 and p38(MAPK) in the postnatal development of the rat visual system.