Chronic administration of SUMO-1 has negative effects on novel object recognition memory as well as cell proliferation and neuroblast differentiation in the mouse dentate gyrus

초록

Post-translational modifications have been associated with developmental and aging processes, as well as in the pathogenesis of certain diseases. The present study aimed to investigate the effects of small ubiquitin-like modifier 1 (SUMO-1) on hippocampal dependent memory function, cell proliferation and neuroblast differentiation. To facilitate the delivery of SUMO-1 into hippocampal neurons, a transactivator of transcription (Tat)-SUMO-1 fusion protein was constructed and mice were divided into two groups: A vehicle (Tat peptide)-treated group and a Tat-SUMO-1-treated group. The vehicle or Tat-SUMO-1 was administered intraperitoneally to 7-week-old mice once daily for 3 weeks, and a novel object recognition test was conducted following the final treatment; the animals were sacrificed 2 h following the test for further analysis. Administration of Tat-SUMO-1 significantly decreased exploration of a new object in a novel object recognition test compared with mice in the vehicle-treated group. In addition, cell proliferation and neuroblast differentiation analyses (based on Ki67 and doublecortin immunohistochemistry, respectively) revealed that the administration of Tat-SUMO-1 significantly reduced cell proliferation and neuroblast differentiation in the dentate gyrus. These results suggested that chronic supplementation of Tat-SUMO-1 affects hippocampal functions by decreasing cell proliferation and neuroblast differentiation in the mouse dentate gyrus.

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