Radiation induces age-dependent deficits in cortical synaptic plasticity
| العنوان: | Radiation induces age-dependent deficits in cortical synaptic plasticity |
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| المؤلفون: | Joseph G. Duman, David R. Grosshans, Die Zhang, Wei Zhou, Connie C. Weng, Patrick M. Dougherty, Thanh Thai Lam, Lawrence Bronk, Duo Ma, Qiang Wang |
| المصدر: | Neuro-Oncology. 20:1207-1214 |
| بيانات النشر: | Oxford University Press (OUP), 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Male, Cancer Research, Long-Term Potentiation, Prefrontal Cortex, Hippocampus, Rats, Sprague-Dawley, 03 medical and health sciences, 0302 clinical medicine, Memantine, Neuroplasticity, Animals, Medicine, Direct pathway of movement, Radiation Injuries, Prefrontal cortex, Neurons, Memory Disorders, Neuronal Plasticity, business.industry, Age Factors, Glutamate receptor, Long-term potentiation, Rats, Oncology, 030220 oncology & carcinogenesis, Basic and Translational Investigations, Synaptic plasticity, Neurology (clinical), Cranial Irradiation, business, Excitatory Amino Acid Antagonists, Neuroscience, 030217 neurology & neurosurgery, medicine.drug |
| الوصف: | Background Radiation-induced cognitive dysfunction is a significant side effect of cranial irradiation for brain tumors. Clinically, pediatric patients are more vulnerable than adults. However, the underlying mechanisms of dysfunction, including reasons for age dependence, are still largely unknown. Previous studies have focused on the loss of hippocampal neuronal precursor cells and deficits in memory. However, survivors may also experience deficits in attention, executive function, or other non-hippocampal-dependent cognitive domains. We hypothesized that brain irradiation induces age-dependent deficits in cortical synaptic plasticity. Methods In vivo recordings were used to test neuronal plasticity along the direct pathway from the cornu ammonis 1 (CA1)/subicular region to the prefrontal cortex (PFC). Specifically, long-term potentiation (LTP) in the CA1/subicular-PFC pathway was assessed after cranial irradiation of juvenile and adult Sprague Dawley rats. We further assessed a potential role for glutamate toxicity by evaluating the potential neuroprotective effects of memantine. Results LTP was greatly inhibited in both adult and juvenile animals at 3 days after radiation but returned to near-normal levels by 8 weeks-only in adult rats. Memantine given before, but not after, irradiation partially prevented LTP inhibition in juvenile and adult rats. Conclusion Cranial radiation impairs neuroplasticity along the hippocampal-PFC pathway; however, its effects vary by age. Pretreatment with memantine offered protection to both juvenile and adult animals. Deficits in cortical plasticity may contribute to radiation-induced cognitive dysfunction, including deficits in attention and age-dependent sensitivity of such pathways, which may underlie differences in clinical outcomes between juveniles and adults after cranial irradiation. |
| تدمد: | 1523-5866 1522-8517 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::263f08d312a022e5b3684e7990d6a4d4 https://doi.org/10.1093/neuonc/noy052 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....263f08d312a022e5b3684e7990d6a4d4 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15235866 15228517 |
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