Neuropsychobiological Mechanisms of Affective and Cognitive Disorders in the Chornobyl Clean-Up Workers Taking Into Account the Specific Gene Polymorphisms

Loganovsky, K.; Mo, Bomko; Abramenko,; Kv, Kuts; Ni, Belous; Masiuk, Sergii; Mv, Gresko; Tk, Loganovska; Ky, Antypchuk; Perchuk,; Gy, Kreinis; Chumak, Stanislav

doi:10.33145/2304-8336-2018-23-373-409

Cited by 16 publications

(4 citation statements)

References 66 publications

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“…Survivors of major nuclear accidents or war may experience brain damage and depression [ 1 , 2 , 47 , 48 ]. In Chernobyl clean-up workers and liquidators with depression, the radiation-induced dysfunction of the cortico-limbic system in the left dominant hemisphere of the brain, with a specific involvement of the hippocampus, is considered to be the key cerebral basis of post-radiation brain damage [ 1 , 2 , 47 , 48 ]. Patients with depressive symptoms have smaller dentate gyrus [ 5 ].…”

Section: Discussionmentioning

confidence: 99%

Early Life Irradiation-Induced Hypoplasia and Impairment of Neurogenesis in the Dentate Gyrus and Adult Depression Are Mediated by MicroRNA- 34a-5p/T-Cell Intracytoplasmic Antigen-1 Pathway

Wang

Shen

et al. 2021

Cells

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Early life radiation exposure causes abnormal brain development, leading to adult depression. However, few studies have been conducted to explore pre- or post-natal irradiation-induced depression-related neuropathological changes. Relevant molecular mechanisms are also poorly understood. We induced adult depression by irradiation of mice at postnatal day 3 (P3) to reveal hippocampal neuropathological changes and investigate their molecular mechanism, focusing on MicroRNA (miR) and its target mRNA and protein. P3 mice were irradiated by γ-rays with 5Gy, and euthanized at 1, 7 and 120 days after irradiation. A behavioral test was conducted before the animals were euthanized at 120 days after irradiation. The animal brains were used for different studies including immunohistochemistry, CAP-miRSeq, Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) and western blotting. The interaction of miR-34a-5p and its target T-cell intracytoplasmic antigen-1 (Tia1) was confirmed by luciferase reporter assay. Overexpression of Tia1 in a neural stem cell (NSC) model was used to further validate findings from the mouse model. Irradiation with 5 Gy at P3 induced depression in adult mice. Animal hippocampal pathological changes included hypoplasia of the infrapyramidal blade of the stratum granulosum, aberrant and impaired cell division, and neurogenesis in the dentate gyrus. At the molecular level, upregulation of miR-34a-5p and downregulation of Tia1 mRNA were observed in both animal and neural stem cell models. The luciferase reporter assay and gene transfection studies further confirmed a direct interaction between miR-43a-5p and Tia1. Our results indicate that the early life γ-radiation-activated miR-43a-5p/Tia1 pathway is involved in the pathogenesis of adult depression. This novel finding may provide a new therapeutic target by inhibiting the miR-43a-5p/Tia1 pathway to prevent radiation-induced pathogenesis of depression.

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Section: Discussionmentioning

confidence: 99%

Early Life Irradiation-Induced Hypoplasia and Impairment of Neurogenesis in the Dentate Gyrus and Adult Depression Are Mediated by MicroRNA- 34a-5p/T-Cell Intracytoplasmic Antigen-1 Pathway

Wang

Shen

et al. 2021

Cells

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“…Interestingly, depressive syndromes are also one of the most frequent long-term effects of atomic bombings, nuclear testing and radiation accidents [104,105]. Incidentally, it is noteworthy that in exposed subjects developing affective and cognitive disorders, we could detect an association between IR and polymorphisms of the serotonin transporter gene SLC6A4, being serotonin, the main neurotransmitter involved in depression [105].…”

Section: Discussionmentioning

confidence: 99%

Radiation-Induced Cerebro-Ophthalmic Effects in Humans

Loganovsky

Marazziti

Fedirko

et al. 2020

Life

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Exposure to ionizing radiation (IR) could affect the human brain and eyes leading to both cognitive and visual impairments. The aim of this paper was to review and analyze the current literature, and to comment on the ensuing findings in the light of our personal contributions in this field. The review was carried out according to the PRISMA guidelines by searching PubMed, Scopus, Embase, PsycINFO and Google Scholar English papers published from January 2000 to January 2020. The results showed that prenatally or childhood-exposed individuals are a particular target group with a higher risk for possible radiation effects and neurodegenerative diseases. In adulthood and medical/interventional radiologists, the most frequent IR-induced ophthalmic effects include cataracts, glaucoma, optic neuropathy, retinopathy and angiopathy, sometimes associated with specific neurocognitive deficits. According to available information that eye alterations may induce or may be associated with brain dysfunctions and vice versa, we propose to label this relationship “eye-brain axis”, as well as to deepen the diagnosis of eye pathologies as early and easily obtainable markers of possible low dose IR-induced brain damage.

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“…The most severe deficits were seen in those with doses above 500 mGy ( Bazyka et al, 2015 ). Follow-up studies of the Ukrainian Chernobyl cleanup workers also suggest a dose-dependent increase in cognitive impairment from radiation exposure ( Loganovsky et al, 2018 , 2020 ). However, in Estonian Chernobyl cleanup workers, there was no difference in morbidity for mental disorders in exposed compared with unexposed cohorts ( Rahu et al, 2014 ).…”

Section: Evidence Base Describing the Impact Of Ionizing Radiation On...mentioning

confidence: 99%

Ionizing radiation, cerebrovascular disease, and consequent dementia: A review and proposed framework relevant to space radiation exposure

Miller

Mi²,

Nelson³

et al. 2022

Front. Physiol.

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Space exploration requires the characterization and management or mitigation of a variety of human health risks. Exposure to space radiation is one of the main health concerns because it has the potential to increase the risk of cancer, cardiovascular disease, and both acute and late neurodegeneration. Space radiation-induced decrements to the vascular system may impact the risk for cerebrovascular disease and consequent dementia. These risks may be independent or synergistic with direct damage to central nervous system tissues. The purpose of this work is to review epidemiological and experimental data regarding the impact of low-to-moderate dose ionizing radiation on the central nervous system and the cerebrovascular system. A proposed framework outlines how space radiation-induced effects on the vasculature may increase risk for both cerebrovascular dysfunction and neural and cognitive adverse outcomes. The results of this work suggest that there are multiple processes by which ionizing radiation exposure may impact cerebrovascular function including increases in oxidative stress, neuroinflammation, endothelial cell dysfunction, arterial stiffening, atherosclerosis, and cerebral amyloid angiopathy. Cerebrovascular adverse outcomes may also promote neural and cognitive adverse outcomes. However, there are many gaps in both the human and preclinical evidence base regarding the long-term impact of ionizing radiation exposure on brain health due to heterogeneity in both exposures and outcomes. The unique composition of the space radiation environment makes the translation of the evidence base from terrestrial exposures to space exposures difficult. Additional investigation and understanding of the impact of low-to-moderate doses of ionizing radiation including high (H) atomic number (Z) and energy (E) (HZE) ions on the cerebrovascular system is needed. Furthermore, investigation of how decrements in vascular systems may contribute to development of neurodegenerative diseases in independent or synergistic pathways is important for protecting the long-term health of astronauts.

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Neuropsychobiological Mechanisms of Affective and Cognitive Disorders in the Chornobyl Clean-Up Workers Taking Into Account the Specific Gene Polymorphisms

Cited by 16 publications

References 66 publications

Early Life Irradiation-Induced Hypoplasia and Impairment of Neurogenesis in the Dentate Gyrus and Adult Depression Are Mediated by MicroRNA- 34a-5p/T-Cell Intracytoplasmic Antigen-1 Pathway

Early Life Irradiation-Induced Hypoplasia and Impairment of Neurogenesis in the Dentate Gyrus and Adult Depression Are Mediated by MicroRNA- 34a-5p/T-Cell Intracytoplasmic Antigen-1 Pathway

Radiation-Induced Cerebro-Ophthalmic Effects in Humans

Ionizing radiation, cerebrovascular disease, and consequent dementia: A review and proposed framework relevant to space radiation exposure

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