Abstract
Therapeutic irradiation of the brain is a common treatment modality for brain tumors, but can lead to impairment of cognitive function. Dendritic spines are sites of excitatory synaptic transmission and changes in spine structure and number are thought to represent a morphological correlate of altered brain functions associated with hippocampal dependent learning and memory. To gain some insight into the temporal and sub region specific cellular changes in the hippocampus following brain irradiation, we investigated the effects of 10 Gy cranial irradiation on dendritic spines in young adult mice. One week or 1 month post irradiation, changes in spine density and morphology in dentate gyrus (DG) granule and CA1 pyramidal neurons were quantified using Golgi staining. Our results showed that in the DG, there were significant reductions in spine density at both 1 week (11.9%) and 1 month (26.9%) after irradiation. In contrast, in the basal dendrites of CA1 pyramidal neurons, irradiation resulted in a significant reduction (18.7%) in spine density only at 1 week post irradiation. Analysis of spine morphology showed that irradiation led to significant decreases in the proportion of mushroom spines at both time points in the DG as well as CA1 basal dendrites. The proportions of stubby spines were significantly increased in both the areas at 1 month post irradiation. Irradiation did not alter spine density in the CA1 apical dendrites, but there were significant changes in the proportion of thin and mushroom spines at both time points post irradiation. Although the mechanisms involved are not clear, these findings are the first to show that brain irradiation of young adult animals leads to alterations in dendritic spine density and morphology in the hippocampus in a time dependent and region specific manner.
Highlights
Cranial irradiation is an essential therapeutic tool in the treatment of primary and secondary malignancies, but can be associated with a risk for adverse side effects, including cognitive dysfunction [1] which can severely affect quality of life [2]
In the basal dendrites of CA1 pyramidal neurons, irradiation resulted in a significant reduction (18.7%, p,0.001) in spine density only at 1 week post irradiation while changes observed at 1 month were not statistically significant (Fig. 3C & D)
The present study demonstrated that brain irradiation altered spine density as well as the proportion of morphological subtypes in the dendrites of dentate gyrus (DG) granule neurons and basal dendrites of CA1 pyramidal neurons in a time dependent manner
Summary
Cranial irradiation is an essential therapeutic tool in the treatment of primary and secondary malignancies, but can be associated with a risk for adverse side effects, including cognitive dysfunction [1] which can severely affect quality of life [2]. The hippocampus plays a crucial role in learning and memory [4] and considerable data exist showing that irradiation leads to impairment of those functions [5,6,7]. This structure is composed of anatomically distinct but functionally interrelated subfields consisting of different cell types, cell sizes, neural connectivity, electrophysiological properties and susceptibility to insult [8]. There have been reports suggesting differences in responses between the CA1 pyramidal cells and DG granule cells after given injurious stimulus [13], but there is a paucity of information regarding sub region specificity in the effects of irradiation on the hippocampus
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