Resumo

The amyloid precursor protein (APP) plays a central role in Alzheimer's disease (AD), an age-related, progressive degenerative disorder that is characterized by synapse and neuron loss in the brain. APP is also involved in important biological processes such as synaptic formation and neural plasticity. APP is cleaved by two different proteolytic pathways leading to the formation of neuroprotective soluble fragments such as α-secretase-derived extracellular fragment (sAPPα) and neurotoxic, small oligomeric amyloid forms of Aβ peptide. The precise mechanism of AD pathogenicity remains to be established, but is well-known that an imbalance in these two major pathways leads to increased release of Aβ, as well as a reduction in the sAPPα formation. Recent reports indicate that matrix metalloproteinases (MMPs), especially metalloproteinase-9, have an α-secretase-like activity. The superior colliculi (SC) has been used as a model to study the mechanisms of synaptic specificity formation during development and plasticity. Our group has demonstrated a higher content in APP levels in the rat superior colliculus until the third postnatal week, a period in which retinotectal axons undergo use-dependent remodeling, leading to precise patterns of connections. Uncrossed retinotectal axons also undergo plasticity under conditions such as monocular enucleation (ME) of the contralateral eye. Our previous results demonstrated that after the critical period ME induced a reduction (50% of control) in APP content with a slow, three-week recovery. OBJECTIVES: Our goals were to verify the activity of MMPs in the superior colliculi of animals after ME-induced plasticity and correlate these data with the expression of APP after ME. METHODS: Lister Hooded rats were submitted to ME at postnatal day 21 (PND21). After different survival times, the animals were sacrificed and the superficial layers of the superior colliculi extracted and processed for zymography analysis. RESULTS: The results showed the highest MMP-9 activity in the SC two weeks after ME with decreasing activity afterwards. This time course correlates with the reorganization of the uncrossed retinotectal projection following ME. Interestingly, the rise in MMP-9 activity precedes the increase in APP expression that peaks three weeks after ME. CONCLUSIONS: Due to the possible α-secretase-like activity of MMP-9 and the already known neurotrophic effects of sAPPα, we suppose that the increase in APP content three weeks after the ME is due to a greater release of sAPPα, mediated by MMP-9 that would be important to the structural reorganization that occurs at the SC after induced plasticity.