Repeated administration of PEP-1-Cu,Zn-superoxide dismutase and PEP-1-peroxiredoxin-2 to senescent mice induced by D-galactose improves the hippocampal functions.

Abstract

Oxidative stress initiates age-related reduction in hippocampal neurogenesis and the use of antioxidants has been proposed as an effective strategy to prevent or attenuate the reduction of neurogenesis in the hippocampus. In the present study, we investigated the effects of Cu,Zn-superoxide dismutase (SOD1) and/or peroxiredoxin-2 (PRX2) on cell proliferation and neuroblast differentiation in the dentate gyrus in a model of D-galactose-induced aging model. For this study, we constructed an expression vector, PEP-1, fused PEP-1 with SOD1 or PRX2, and generated PEP-1-SOD1 and PEP-1-PRX2 fusion protein. The aging model was induced by subcutaneous injection of D-galactose (100 mg/kg) to 6-week-old male mice for 10 weeks. PEP-1, PEP-1-SOD1 and/or PEP-1-PRX2 fusion protein was intraperitoneally administered to these mice at 13-week-old once a day for 3 weeks and sacrificed at 30 min after the last administrations. The administration of PEP-1-SOD1 and/or PEP-1-PRX2 significantly improved D-galactose-induced deficits on the escape latency, swimming speeds, platform crossings, spatial preference for the target quadrant in Morris water maze test. In addition, the administration of PEP-1-SOD1 and/or PEP-1-PRX2 ameliorated D-galactose-induced reductions of cell proliferation and neuroblast differentiation in the dentate gyrus and significantly reduced D-galactose-induced lipid peroxidation in the hippocampus. These effects were more prominent in the PEP-1-SOD1-treated group with PEP-1-PRX2. These results suggest that a SOD1 and/or PRX2 supplement to aged mice could improve the memory deficits, cell proliferation and neuroblast differentiation in the dentate gyrus of D-galactose induced aged mice by reducing lipid peroxidation.

• Authors: Jung Hoon Choi, Dae Won Kim, Dae Young Yoo, Hoon Jae Jeong, Woosuk Kim, Hyo Young Jung, Sung Min Nam, Jong Hwi Kim, Yeo Sung Yoon, Soo Young Choi, In Koo Hwang
• Journal: Neurochemical research (Neurochem Res) Vol. 38 Issue 10 Pg. 2046-55 (Oct 2013) ISSN: 1573-6903 [Electronic] United States
• PMID: 23892988 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Neuroprotective Agents
• Pep-1 peptide
• Peptides
• Recombinant Fusion Proteins
• Cysteamine
• Peroxiredoxins
• Sod1 protein, mouse
• Superoxide Dismutase
• Superoxide Dismutase-1
• Galactose

Topics

• Aging (drug effects)
• Animals
• Antioxidants (pharmacology)
• Cell Differentiation (drug effects)
• Cell Proliferation (drug effects)
• Cysteamine (administration & dosage, analogs & derivatives)
• Galactose (toxicity)
• Hippocampus (drug effects, physiology)
• Lipid Peroxidation (drug effects)
• Male
• Maze Learning (drug effects)
• Memory Disorders (chemically induced)
• Mice
• Neurogenesis
• Neuroprotective Agents (pharmacology)
• Oxidative Stress (drug effects)
• Peptides (administration & dosage)
• Peroxiredoxins (administration & dosage)
• Recombinant Fusion Proteins (administration & dosage)
• Superoxide Dismutase (administration & dosage)
• Superoxide Dismutase-1