Open Access

Increased hippocampal TrkA expression ameliorates cranial radiation‑induced neurogenesis impairment and cognitive deficit via PI3K/AKT signaling

  • Authors:
    • Shengjun Ji
    • Haohao Wu
    • Xin Ding
    • Qingqing Chen
    • Xing Jin
    • Jinming Yu
    • Ming Yang
  • View Affiliations

  • Published online on: September 28, 2020     https://doi.org/10.3892/or.2020.7782
  • Pages: 2527-2536
  • Copyright: © Ji et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cognitive deficit is one of the most serious complications of cranial radiotherapy of head and neck cancers. However, the underlying mechanism of this cognitive impairment remains unclear. In the present study, the role of tropomyosin receptor kinase A (TrkA) and its ligand neurotrophin nerve growth factor (NGF) were investigated following whole‑brain irradiation (WBI). Young male Sprague‑Dawley rats underwent WBI at a single dose of 10 Gy. WBI was determined to result in notable memory decline and substantial neurogenesis impairment in the hippocampus 3 months post‑irradiation. Compared with the control group, TrkA protein expression was greater in irradiated rats 1 week after WBI, which then decreased significantly by the 3‑month time‑point. However, no difference in NGF expression was observed from 1 day to 3 months post‑WBI. Overexpression of hippocampal TrkA in rats using adeno‑associated virus ameliorated memory decline induced by irradiation. Additionally, upregulating TrkA expression rescued irradiation‑induced hippocampal precursor cell proliferation and promoted neurogenesis. PI3K, Akt and ERK1/2 phosphorylation were also revealed to be significantly inhibited by WBI, which was ameliorated by TrkA overexpression. Findings of the present study indicated that the TrkA‑dependent signaling pathway may serve a critical role in radiotherapy‑induced cognitive deficit and impairments in neurogenesis.
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December-2020
Volume 44 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Ji S, Wu H, Ding X, Chen Q, Jin X, Yu J and Yang M: Increased hippocampal TrkA expression ameliorates cranial radiation‑induced neurogenesis impairment and cognitive deficit via PI3K/AKT signaling. Oncol Rep 44: 2527-2536, 2020
APA
Ji, S., Wu, H., Ding, X., Chen, Q., Jin, X., Yu, J., & Yang, M. (2020). Increased hippocampal TrkA expression ameliorates cranial radiation‑induced neurogenesis impairment and cognitive deficit via PI3K/AKT signaling. Oncology Reports, 44, 2527-2536. https://doi.org/10.3892/or.2020.7782
MLA
Ji, S., Wu, H., Ding, X., Chen, Q., Jin, X., Yu, J., Yang, M."Increased hippocampal TrkA expression ameliorates cranial radiation‑induced neurogenesis impairment and cognitive deficit via PI3K/AKT signaling". Oncology Reports 44.6 (2020): 2527-2536.
Chicago
Ji, S., Wu, H., Ding, X., Chen, Q., Jin, X., Yu, J., Yang, M."Increased hippocampal TrkA expression ameliorates cranial radiation‑induced neurogenesis impairment and cognitive deficit via PI3K/AKT signaling". Oncology Reports 44, no. 6 (2020): 2527-2536. https://doi.org/10.3892/or.2020.7782