STEAP proteins were recently shown to function as metalloreductases. STEAP3 is widely expressed in the body and overexpression stimulates the reduction of iron. However, the electrical cortical responses were not recorded in this study, making it difficult to compare with our results. Finally, there was no significant difference between the effect of CPP and the one of i.c. scopolamine in terms of VEP amplitude. This might indicate an all-or-none effect on VEP enhancement, suggesting common intracellular pathways leading to LTP. We propose that activation of mAChRs interact with intracellular NMDAR pathways to induce cholinergic-induced long-term effects on VEPs. It has been shown that M1 and M3 interact with NMDAR pathways in the hippocampus by elevating intracellular Ca2+ levels and thereby enhancing the AMPA receptor currents. Post-synaptic mAChRs on pyramidal or spiny stellate cells are able to induce PKC or AKT. Moreover, in vitro induction of LTP in V1 slices is impaired in M2/M4 mAChRs double knock-out mice, suggesting that inhibition of M2/M4 mAChRs impaired LTP. Alternatively, the long-term enhancement of VEP could result from an increase in VEP amplitude most likely due to the number and nature of cells involved or a change in the balance between LTP/LTD mechanisms induced. In this case, the inhibition of the different subtypes of mAChRs located on different cell types could result in a decreased number of excitatory cells activated by the paired visual Trichostatin A stimulation and CCh infusion. The third gene, which was upregulated by a factor 3.0, was MT2A and is involved in induction of apoptosis, an important feature in IBD not only for the inflammation but also for malignant transformation. Further, the MT2A protein possess a protection against oxidation injury in particular in inflammatory conditions, which might be of importance for the clinical course of CD. Metallothioneins moreover comprise a family of cysteine-rich low molecular weight proteins that form complexes with heavy metal ions such as zinc and copper, but also xenobiotic heavy metals such as mercury, silver and cadmium. Recent data have shown that placental MT2 isoform is upregulated in response to smoking. Cigarette smoke contains about 30 different metal ions including cadmium, zinc, arsene, copper, aluminium, antimony, lead, nickel, chromium and iron. Many metals are reactive and promote oxidative stress and leading to toxic effects and carcinogenesis. Taken together, the upregulation of STEAP3 and MT2 isoform may result from an increased load of metal ions including ferric ions. Apart from local hypersensitivity reactions it is unknown if metalions promote inflammation, but our results indicate that metal ions might play a role in CD. By siRNA-mediated knockdown, overexpression, and deletion analysis of the dPRL enhancer, we identified HoxA-11 as a direct regulator of PRL expression.