1. Radiation induces age-dependent deficits in cortical synaptic plasticity.
- Author
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Zhang D, Zhou W, Lam TT, Weng C, Bronk L, Ma D, Wang Q, Duman JG, Dougherty PM, and Grosshans DR
- Subjects
- Age Factors, Animals, Excitatory Amino Acid Antagonists pharmacology, Hippocampus drug effects, Hippocampus radiation effects, Long-Term Potentiation drug effects, Long-Term Potentiation radiation effects, Male, Memory Disorders drug therapy, Memory Disorders etiology, Neuronal Plasticity drug effects, Neurons drug effects, Neurons radiation effects, Prefrontal Cortex drug effects, Prefrontal Cortex radiation effects, Radiation Injuries prevention & control, Rats, Rats, Sprague-Dawley, Cranial Irradiation adverse effects, Hippocampus pathology, Memantine pharmacology, Memory Disorders pathology, Neuronal Plasticity radiation effects, Neurons pathology, Prefrontal Cortex pathology
- Abstract
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.
- Published
- 2018
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