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Cranial Irradiation Alters Dendritic Spine Density and morphology in the Hippocampus PLoS ONE | 1 July 2012 | Volume 7 | Issue 7 | e40844 Cranial Irradiation Alters Dendritic Spine Density and morphology in the Hippocampus Ayanabha Chakraborti1,4, Antino Allen1,4, Barrett Allen1,4, Susanna Rosi1,3,4, John R. Fike1,2,4* Cranial irradiation is an essential therapeutic tool in the treatment of malignancies, but can be associated with a risk of adverse effects, including cognitive dysfunction. The hippocampus plays crucial role in learning and memory and irradiation leads to impairment of those functions. The purpose of the present study was to determine the temporal effects of cranial irradiation on spine density and morphology in the dendrites of granule neurons of dentate gyrus as well as Pyramidal neurons of CA1 area of the hippocampus. Spine analyses were conducted separately in the apical and basal dendrites. The study was used a total of 20, two month old male C57BL/6J mice. Mice were irradiated with a single dose of 10 Gy, and then one week or 1 month post Irradiation the animal were euthanized by cervical dislocation. For spine analyses, Golgi staining was performed. Spines were examined on dendrites of DG granule neurons as well as apical (stratum radiatum) and basal (stratum oriens) dendrites of CA1 pyramidal neurons. On the basis morphology, spines were classified into the following categories: i). Thin: spines with a long neck and a visible small head; ii). Mushroom: big spines with a well-defined neck and a very voluminous head; and iii). Stubby: very short spines without a distinguishable neck and stubby appearance. For spine analyses they were focuses on spines that are parallel to the plane section. Results are in DG there were significant reduction changes in dendritic spine density after radiation exposure, at both 1 week and 1 month. In contrast, in the basal dendrites of CA1 pyramidal neurons, a significant reduction of spine density only at 1 weeks post Irradiation. In the DG, 1 weeks after irradiation, there was a significant increase in the proportion of thin Spines. On the other hand, the proportion of mushroom spines was significantly reduced at both 1 week and 1 month after irradiation, and the proportion of stubby spines was significantly increased only at 1 month post irradiation. In the CA1 basal dendrites, irradiation significantly increased the proportion of thin spines at 1 week. On the other hand the proportion of mushroom spines was significantly reduced at both one week and one month. Contrary to what was found in DG and CA1 basal dendrites, there was a significant decrease in the proportion of thin spines at both time point, and a significant increase in proportion of mushroom spines at both time point after irradiation. In conclusion, cranial irradiation causes alteration in spine density and morphology in the hippocampus in a time dependent and region specific manner.
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