Increased hippocampal TrkA expression ameliorates cranial radiation‑induced neurogenesis impairment and cognitive deficit via PI3K/AKT signaling
Autor: | Ming Yang, Xin Ding, Haohao Wu, Jinming Yu, Shengjun Ji, Xing Jin, Qingqing Chen |
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Rok vydání: | 2020 |
Předmět: |
Male
0301 basic medicine Cancer Research medicine.medical_specialty hippocampus Neurogenesis Genetic Vectors cranial radiotherapy Tropomyosin receptor kinase A Hippocampal formation memory Stereotaxic Techniques 03 medical and health sciences 0302 clinical medicine tropomyosin receptor kinase A Internal medicine Nerve Growth Factor medicine Animals Humans Cognitive Dysfunction Receptor trkA Protein kinase B Cognitive deficit PI3K/AKT/mTOR pathway biology business.industry Articles General Medicine Dependovirus Rats Radiation Injuries Experimental 030104 developmental biology Endocrinology Nerve growth factor nervous system Oncology Head and Neck Neoplasms 030220 oncology & carcinogenesis biology.protein Cranial Irradiation medicine.symptom business Signal Transduction Neurotrophin |
Zdroj: | Oncology Reports |
ISSN: | 1791-2431 1021-335X |
Popis: | 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. |
Databáze: | OpenAIRE |
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