4.7 Article

Baicalein attenuates impaired hippocampal neurogenesis and the neurocognitive deficits induced by gamma-ray radiation

Journal

BRITISH JOURNAL OF PHARMACOLOGY
Volume 168, Issue 2, Pages 421-431

Publisher

WILEY
DOI: 10.1111/j.1476-5381.2012.02142.x

Keywords

brain tumour; radiotherapy; cell death; neural progenitor cell; neurogenesis; oxidative stress; whole-brain irradiation

Funding

  1. Basic Science Research Program via the National Research Foundation of Korea (NRF)
  2. Ministry of Education, Science and Technology [2009-0067608]
  3. National Research Foundation of Korea (NRF)
  4. Korea government (MEST) [20090083538]

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BACKGROUND AND PURPOSE Whole-brain irradiation (WBI) therapy produces learning and memory deficits in patients with brain tumours. Although the pathological cascade of cognitive deficits remains unknown, it may involve reduced neurogenesis within the hippocampus. Baicalein is a flavonoid derived from the roots of Huangqin, Scutellaria baicalensis Georgi, and has been shown to have antioxidant effects. Here, we have investigated the protective effects of baicalein on irradiation-induced impairments in hippocampal neurogenesis and cognitive function. EXPERIMENTAL APPROACH Radioprotective effects of baicalein were evaluated in C17.2 neural progenitor cells and 6-week-old male C57BL/6 mice during hippocampal neurogenesis. Mice were given a single dose of 5 Gy WBI. Changes in hippocampal neurogenesis, oxidative stress and BDNF-pCREB signalling were evaluated. Morris water maze and passive avoidance test were used to assess learning and memory. KEY RESULTS Baicalein protected neural progenitor cells against irradiation-induced necrotic cell death. Pretreatment with baicalein attenuated the irradiation-induced impairment of hippocampal neurogenesis by modulating oxidative stress and elevating BDNF-pCREB signalling. Furthermore, baicalein prevented the spatial learning and memory retention deficits follwing WBI. CONCLUSIONS AND IMPLICATIONS Our findings suggest that baicalein can be viewed as a potential therapeutic agent that protects against the impaired neurogenesis induced by WBI, and its neurocognitive consequences.

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