Exp Mol Med.  2018 Mar;50(3):e461. 10.1038/emm.2017.302.

Intrahippocampal injection of a lentiviral vector expressing neurogranin enhances cognitive function in 5XFAD mice

Affiliations
  • 1Department of Biochemistry, College of Medicine, Konyang University, Daejeon, Republic of Korea. hominmoon@konyang.ac.kr
  • 2Graduate School of New Drug Discovery and Development, Chungnam National University, Daejeon, Republic of Korea.
  • 3Department of New Drug Discovery and Development, Chungnam National University, Daejeon, Republic of Korea.
  • 4Department of Medicinal Biotechnology, College of Health Sciences, Dong-A University, Busan, Republic of Korea.
  • 5Department of Biochemistry and Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.

Abstract

Progressive cognitive declines are the main clinical symptoms of Alzheimer's disease (AD). Cognitive impairment in AD is directly correlated with amyloid beta (Aβ)-mediated synaptic deficits. It is known that upregulation of neurogranin (Ng), a postsynaptic protein, contributes to the enhancement of synaptic plasticity and cognitive function. By contrast, downregulation of Ng expression results in learning and memory impairments. Interestingly, Ng expression is significantly reduced in the parenchyma of brains with AD. However, the pathological role that downregulated Ng plays in the cognitive dysfunctions observed in AD remains unclear. Therefore, the present study examined whether enhancing Ng expression affected cognitive functions in 5XFAD mice, an animal model of AD. We found that the Ng reductions and cognitive decline observed in 5XFAD mice were restored in mice that were intrahippocampally injected with an Ng-expressing lentiviral vector. Furthermore, overexpression of Ng upregulated expression of postsynaptic density protein-95 in the hippocampus of 5XFAD mice. These results suggest that the cause of cognitive decline in AD may be at least partially associated with reduced Ng levels, and thus, supplementation of Ng may be an appropriate therapeutic strategy for individuals with AD.

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