Induction by Single Low-dose Irradiations of Acute Transcriptional Alterations in Several Alzheimer's Disease-Related Genes without Significant Late Consequences on Behavioral and Brain Pathological Changes in Mice

Alzheimer's disease (AD) is the most common form of dementia while its cause and progression are not well understood. The possible cognitive and behavioral consequences induced by low-dose radiation are of great concern as humans are exposed to ionizing radiations from various sources including medical diagnosis. A recent study in mice reported early transcriptional response in brain to low-dose X-rays (0.1Gy) suggesting alterations of molecular networks and pathways associated with cognitive functions, advanced aging and AD. To investigate the cognitive and behavioral consequences induced by low doses, C57BL/6J mice were whole-body irradiated with either X-rays (0.1Gy) or accelerated carbon ions (0.05 Gy or 0.1 Gy). The hippocampus was collected and the expression of AD-related genes was analyzed. Morris Water maze test was applied to the measurement of the learning ability and memory of the animals. Amyloid imaging with positron emission tomography (PET) were performed to detect the accumulation of fibrillary amyloid beta peptide, and characteristic pathologies of AD were examined with immunohistochemical staining of amyloid precursor protein (APP), amyloid beta peptide, tau and phosphorylated tau. Results showed significant acute transcriptional alterations in several AD-related genes at 4 h after irradiation while no marked changes 1 yr later. No significant difference on learning ability and memory was observed 1 yr after irradiation. Imaging and immunohistochemical staining showed that no change in the accumulation of fibrillar amyloid and the expression of APP, amyloid beta peptide, tau, phosphorylated tau were not detectable in the animals 4 m and 2 yr after irradiation. These findings suggest that low-dose irradiations could induce acute transcriptional alterations in several AD-related genes without significant late consequences on behavioral and AD-related pathological changes in mice.