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Functional Interrogation of Adult Hypothalamic Neurogenesis with Focal Radiological Inhibition
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Cranial irradiation inhibits hippocampal neurogenesis via DNMT1 and DNMT3A

Shengjun Ji1, Xin Ding2, Jiang Ji2

  • 1Cancer Center, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, Jiangsu 215001, P.R. China.

Oncology Letters
|February 14, 2018
PubMed

Insights

Whole-brain radiation impairs hippocampal neurogenesis, a key factor in cognitive dysfunction. This study suggests DNA methyltransferases (DNMTs) like DNMT1 and DNMT3A play a role in this radiation-induced neurogenesis impairment.

Area of Science:

  • Neuroscience
  • Radiation Biology
  • Epigenetics

Background:

  • Whole-brain irradiation impairs hippocampal neurogenesis, leading to cognitive dysfunction.
  • The exact mechanisms behind radiation-induced cognitive impairment and potential therapeutic targets remain unclear.
  • DNA methylation, regulated by DNA methyltransferases (DNMTs), influences neuronal function and plasticity.

Purpose of the Study:

  • To investigate the role of DNMTs in radiation-induced impairment of hippocampal neurogenesis.
  • To explore DNMT1 and DNMT3A as potential therapeutic targets for mitigating radiation-induced cognitive dysfunction.

Main Methods:

  • Utilized Sprague-Dawley rats divided into control, radiation, zebularine (DNMT inhibitor), and combined treatment groups.
  • Employed immunofluorescence staining to assess cellular proliferation and dendritic growth in hippocampal neurons.
  • Conducted western blot analysis to quantify the expression levels of DNMT1 and DNMT3A proteins.

Main Results:

  • Radiation significantly inhibited cellular proliferation and dendritic growth in new hippocampal neurons.
  • Irradiation led to decreased expression of DNMT1 and DNMT3A proteins in the hippocampus.
  • Co-administration of zebularine with radiation further reduced cell proliferation, dendritic growth, and DNMT1/DNMT3A levels compared to radiation alone.

Conclusions:

  • DNMT1 and DNMT3A are implicated in the pathogenesis of whole-brain radiation-induced neurogenesis impairment.
  • These findings suggest that targeting DNMTs may offer a therapeutic strategy against radiation-induced cognitive deficits.
Keywords:
DNA methyltransferasehippocampusneurogenesisradiation

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