Korean J Physiol Pharmacol.  2016 Jan;20(1):41-51. 10.4196/kjpp.2016.20.1.41.

Epigallocatechin-3-gallate rescues LPS-impaired adult hippocampal neurogenesis through suppressing the TLR4-NF-kappaB signaling pathway in mice

Affiliations
  • 1Dental Science Research Institute, School of Dentistry, Chonnam National University, Gwangju 61186, Korea. wjkim@jnu.ac.kr, jjy@jnu.ac.kr
  • 2Medical Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University, Gwangju 61186, Korea.
  • 3Department of Oral Physiology, School of Dentistry, Chonnam National University, Gwangju 61186, Korea.
  • 4Department of Oral and Maxillofacial Surgery, School of Dentistry, Chonnam National University, Gwangju 61186, Korea.
  • 5Department of Microbiology, Collage of Medicine, Seonam Universtity, Namwon 55724, Korea.

Abstract

Adult hippocampal dentate granule neurons are generated from neural stem cells (NSCs) in the mammalian brain, and the fate specification of adult NSCs is precisely controlled by the local niches and environment, such as the subventricular zone (SVZ), dentate gyrus (DG), and Toll-like receptors (TLRs). Epigallocatechin-3-gallate (EGCG) is the main polyphenolic flavonoid in green tea that has neuroprotective activities, but there is no clear understanding of the role of EGCG in adult neurogenesis in the DG after neuroinflammation. Here, we investigate the effect and the mechanism of EGCG on adult neurogenesis impaired by lipopolysaccharides (LPS). LPS-induced neuroinflammation inhibited adult neurogenesis by suppressing the proliferation and differentiation of neural stem cells in the DG, which was indicated by the decreased number of Bromodeoxyuridine (BrdU)-, Doublecortin (DCX)- and Neuronal Nuclei (NeuN)-positive cells. In addition, microglia were recruited with activatingTLR4-NF-kappaB signaling in the adult hippocampus by LPS injection. Treating LPS-injured mice with EGCG restored the proliferation and differentiation of NSCs in the DG, which were decreased by LPS, and EGCG treatment also ameliorated the apoptosis of NSCs. Moreover, pro-inflammatory cytokine production induced by LPS was attenuated by EGCG treatment through modulating the TLR4-NF-kappaB pathway. These results illustrate that EGCG has a beneficial effect on impaired adult neurogenesis caused by LPSinduced neuroinflammation, and it may be applicable as a therapeutic agent against neurodegenerative disorders caused by inflammation.

Keyword

Adult Neurogenesis; Epigallocatechin-3-gallate; Neural stem cells; Neuronal Inflammation; NF-kappaB signaling; TLR4
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