Although tissue type plasminogen activator (tPA) and brain derived neurotrophic factor (BDNF) have been extensively described to influence brain outcomes in a number of disorders, their roles during physiological aging are poorly investigated. In the present study, we investigated whether maintenance of mice in different environmental conditions could influence age-associated changes in hippocampal tPA expression and BDNF maturation in relation with modifications of their cognitive performances. Our data indicate that maintenance in enriched housing led to a reversal of age-associated decrease in expression of hippocampal tPA. A subsequent increase in the level of mature BDNF and an improvement in emotional and spatial memories were observed. Taken together, these data suggest that the tPA-BDNF axis could play a critical role in the control of cognitive functions influenced both by the age and housing conditions.
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