Background: Major depressive disorder is a highly prevalent psychiatric condition that can be explained by the “neuroplasticity hypothesis” that proposes that stress induces a volumetric reduction of the hippocampus and an altered synaptic transmission. MMP9 is a gelatinase that is released from glutamatergic excitatory synapses after the activation of the NMDA receptor. Its main role is the regulation of processes such as synaptic plasticity, learning and memory. An overexpression of MMP9 leads to an aberrant synaptic plasticity and can be associated with several neuropsychiatric disorders, in particular depression. MMP9 is overactivated in the animal model of “chronic restraint stress” leading to alterations in social behaviours and cognition. Furthermore, human studies reveal increased plasma MMP9 levels in depressed patients compared to healthy subjects. Objectives: In the corticosterone mouse model of depression we will evaluate: 1) the depressive-anxious-like behaviour and 2) the expression and activity of MMP9, and the expression of nectin-3 in hippocampus and cortex. Materials and methods: C57BL/6J male mice were treated with corticosterone (5-10 mg/kg/day, 4-weeks). Different depressive-anxious behavioural tests, MMP9 zymography, and MMP9 and nectin-3 western blot analysis in hippocampus and cortex were performed. Results: The corticosterone model shows a depressive-/anxious-like behaviour compared to control mice. The gelatinase activity of MMP9 is increased in cortex, and shows a tendency in the hippocampus. The protein expression of MMP9 is significantly elevated in both hippocampus and cortex, while the nectin-3 is reduced in this model. A positive correlation is observed in the cortex between immobility in the forced-swimming test and MMP9 activity. Conclusions: The chronic administration of corticosterone induces a depressive-/anxious-like phenotype in mice. This animal model exhibits an increase in the expression and activity of MMP9 in relevant areas implicated in depression. This observation suggests that aberrant MMP9 could have a significant role in this disease.
