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Gene expression, telomere and cognitive deficit analysis as a function of Chornobyl radiation dose and age: from in utero to adulthood.
Published: 12/23/2015, Problemy radiatsiinoi medytsyny ta radiobiolohii
Abstract
Objective - to estimate the possible effects of low dose ionizing radiation on human cognitive function in adult hood and in utero.
Materials And Methods
Cognitive tests, telomere length and expression of genes regulating telomere function were studied in Chornobyl cleanup workers who were exposed to doses under 500 mSv (n = 326) and subjects exposed in utero during the first days after the accident Prypiat town (n = 104). The neurocognitive assessment covered mem ory, attention, language, executive and visiospatial functions. In young adults after prenatal exposure a relation ship was analyzed between a cognitive function and radiation dose to foetus, brain and thyroid gland. Internal con trols were used for both groups - the group of Chornobyl cleanup workers exposed in doses less than 20 mSv and an age matched comparison group from radioactively contaminated areas for subjects exposed in utero.
Results
Cognitive functions in cleanup workers exposed to ionizing radiation at adulthood are characterized by symptoms of a mild cognitive impairment according to the MMSE (mean group score 25,58 ± 2,95) and a significant ly higher level of mental disorders according to the BPRS in a dose related manner. Cleanup workers exposed to doses over 500 mSv demonstrate a significant cognitive deficit in comparison with those exposed below 500 mSv and espe cially non exposed patients. Subjects exposed in utero during the check at age of 25-27 years exhibit an excess of the disorders of autonomic nervous system (ICD 10: G90). Neurological microsymptoms as well as neurotic, stress relat ed and somatoform disorders (F40-F48) dominate. Relationship were revealed between the TERT, TERF1, TERF2 genes expression, relative telomere length (RTL),cognitive deficit and cerebrovascular pathology, radiation dose and age. Telomere length in cleanup workers is sreduced after 50 years (6.1 %). The most significant reduction in telomere length is shown after 70 years (11.7 %). Negative correlation was found between telomere length and degree of cog nitive deficit (MMSE scale) and between age and degree of cognitive deficit. The RTL is significantly decreased in groups of persons with cognitive deficit compared to a comparison group. Telomere length at the late period after low dose radiation exposure is downregulated by the high TERF2 gene expression combined with low expression of TERT gene. After exposure to doses over 250-500 mSv a cognitive deficit and dementia were associated with a substantial increase in TERT gene expression, overexpression of TERF1 and decrease in expression of TERF2 gene. A relationship was revealed between the TERF2 gene expression and CD95+ cell fraction susceptible to apoptosis.
Conclusions
This study shows that cognitive deficit in humans at a late period after radiation exposure is influ enced by dose, age at exposure and gene regulation of telomere function.
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