Fast neutron irradiation deteriorates hippocampus-related memory ability in adult mice

Yang, Miyoung; Kim, Hwanseong; Kim, Juhwan; Kim, Sungho; Kim, Jong-Choon; Bae, Chun‐Sik; Kim, Joong Sun; Shin, Taekyun; Moon, Changjong

doi:10.4142/jvs.2012.13.1.1

Cited by 16 publications

(4 citation statements)

References 17 publications

(39 reference statements)

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“…There has been significant progress in experimental research for detailing the many aspects of radiation impairment of neurogenesis (11–16), by, e.g., high-LET radiation (24–31, 52, 53). However, studies have been limited in the number of doses, postirradiation time points, age at irradiation, and radiation types considered.…”

Section: Discussionmentioning

confidence: 99%

Modeling Heavy-Ion Impairment of Hippocampal Neurogenesis after Acute and Fractionated Irradiation

Cacao

Cucinotta

2016

Radiation Research

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Radiation-induced impairment of neurogenesis in the hippocampal dentate gyrus is a concern due to its reported association with cognitive detriments after radiotherapy for brain cancers and the possible risks to astronauts chronically exposed to space radiation. Here, we have extended our recent work in a mouse model of impaired neurogenesis after exposure to low-linear energy transfer (LET) radiation to heavy ion irradiation. To our knowledge, this is the first report of a predictive mathematical model of radiation-induced changes to neurogenesis for a variety of radiation types after acute or fractionated irradiation. We used a system of nonlinear ordinary differential equations (ODEs) to represent age, time after exposure and dose-dependent changes to several cell populations participating in neurogenesis, as reported in mouse experiments. We considered four compartments to model hippocampal neurogenesis and, consequently, the effects of radiation in altering neurogenesis: 1. neural stem cells (NSCs); 2. neuronal progenitor cells or neuroblasts (NB); 3. immature neurons (ImN); and 4. glioblasts (GB), with additional consideration of microglial activation. The model describes the negative feedback regulation on early and late neuronal proliferation after irradiation, and the dynamics of the age dependence of neurogenesis. We compared our model to experimental data for X rays, and protons, carbon and iron particles, including data for fractionated iron-particle irradiation. Heavy-ion irradiation is predicted to lead to poor recovery or no recovery from impaired neurogenesis at doses as low as 0.5 Gy in mice. This is only partially ameliorated by dose fractionation, which suggests important implications for Hardon therapy near the Bragg peak, and possibly for space radiation exposures as well. Predictions of the threshold doses where neurogenesis recovery fails for given radiation types are described, and the role of subthreshold transient impairments are briefly discussed.

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Section: Discussionmentioning

confidence: 99%

Modeling Heavy-Ion Impairment of Hippocampal Neurogenesis after Acute and Fractionated Irradiation

Cacao

Cucinotta

2016

Radiation Research

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“…Previous reports have suggested that cell death induced by X-irradiation is the underlying cause of delayed memory disturbance in chronic time after X-irradiation (2, 3,33). Ten grays of X-irradiation has been shown to induce cognitive impairments 3 months after the exposure (2).…”

Section: Massive Acute Synaptic Dysfunction Underlies X-irradiation-imentioning

confidence: 99%

“…It seems that changes in presynaptic sites take more time and this suggests that presynaptic sites are more stable than postsynaptic sites. The earlier changes that happen in postsynaptic sites than in presynaptic sites also found in Alzheimer's disease (31, 32).Previous reports have suggested that cell death induced by X-irradiation is the underlying cause of delayed memory disturbance in chronic time after X-irradiation (2, 3,33). Ten grays of X-irradiation has been shown to induce cognitive impairments 3 months after the exposure (2).…”

mentioning

confidence: 97%

X Irradiation Induces Acute Cognitive Decline via Transient Synaptic Dysfunction

et al. 2016

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INTRODUCTIONRadiation therapy is often used for the treatment of brain tumors; however, radiationinduced brain injury, including both anatomical and functional changes, is sometimes observed after the irradiation (1). Radiation-induced brain injury is mostly observed and symptomatically found chronically after radiation therapy, and the main underlying cause is thought to be cell death. The acute effects of irradiation are well known, but very few studies have investigated the underlying mechanisms.Radiation-induced brain injury is classified into acute, early delayed and late delayed injury. Early delayed injuries start to occur more than 1 month after irradiation. For example, progressive depletion of adult neurogenesis in the hippocampus by X-irradiation induces impairment of cognitive function 1-2 months after the exposure (2-4). In contrast, acute injury has been reported to manifest within days of exposure. For example, impairment of long term potentiation has been observed 48 h after -irradiation (5). Because mature neurons are relatively radiation-resistant, the acute effects of injury might be associated with synaptic dysfunction.It has been reported recently that the mislocalization and dysregulation of postsynaptic structural proteins result in synaptopathy (6). We focused on drebrin, a protein whose loss from dendritic spines is a surrogate marker of synaptopathy. In dementias, such as Alzheimer's disease, mild cognitive impairment and Down syndrome, drebrin loss from the dendritic spines 2 of hippocampal neurons is observed (7).Cognitive function strongly correlates with synaptic plasticity (8, 9), and dynamic morphological changes in dendritic spines play an important role in synaptic plasticity.Dendritic spines are actin-rich structures that protrude from dendritic shafts. F-actin in the core of the dendritic spine is stabilized by drebrin, which is an actin-binding protein (10, 11), and regulation of F-actin stability is necessary for synaptic plasticity (12).We recently reported that X-irradiation induces an acute decrease in drebrin in the dendritic spines of cultured hippocampal neurons (13). This suggests that the X-irradiation causes acute alterations in synaptic function. Therefore in the present study, we examined the acute effect of X-irradiation using behavioral and immunohistochemical analyses within 24 h of exposure. MATERIALS AND METHODS AnimalsTen-to 11-week-old male mice were used (C57BL/6N; CLEA Japan, Inc., Japan; SLC Co., Ltd., Shizuoka, Japan). All animal experiments were performed according to guidelines set by the Animal Care and Experimentation Committee (Gunma University, Showa Campus, Maebashi, Japan). We used 10-13 mice per group for behavioral analysis, 3-4 mice (4-7 slices from one animal) per group for immunohistochemical analysis and three mice per group for western blot analysis. The mice were maintained under standard animal facility conditions with 3 food and water available ad libitum. All efforts were made to minimize animal suffering and to reduce the number of ...

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“…The neutron-beam, including fast neutrons, was produced by irradiating a proton beam (20 µA, 35 MeV) on a beryllium target by using a KIRAMS MC-50 cyclotron (Scanditronix, Växjö, Sweden). The mean dose rate for fast neutrons was 94 mGy/min [22]. For in vivo brain imaging, mice were irradiated with a dose of 1 Gy, 5 Gy, and 10 Gy, respectively, using a small animal image-guided irradiation system X-RAD SmART (Precision X-ray Inc., North Branford, CT, USA) [23].…”

Section: Radiation Exposurementioning

confidence: 99%

Image-Based Evaluation of Irradiation Effects in Brain Tissues by Measuring Absolute Electrical Conductivity Using MRI

Kim

Park

Katoch

et al. 2021

Cancers

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Radiation-induced injury is damage to normal tissues caused by unintentional exposure to ionizing radiation. Image-based evaluation of tissue damage by irradiation has an advantage for the early assessment of therapeutic effects by providing sensitive information on minute tissue responses in situ. Recent magnetic resonance (MR)-based electrical conductivity imaging has shown potential as an effective early imaging biomarker for treatment response and radiation-induced injury. However, to be a tool for evaluating therapeutic effects, validation of its reliability and sensitivity according to various irradiation conditions is required. We performed MR-based electrical conductivity imaging on designed phantoms to confirm the effect of ionizing radiation at different doses and on in vivo mouse brains to distinguish tissue response depending on different doses and the elapsed time after irradiation. To quantify the irradiation effects, we measured the absolute conductivity of brain tissues and calculated relative conductivity changes based on the value of pre-irradiation. The conductivity of the phantoms with the distilled water and saline solution increased linearly with the irradiation doses. The conductivity of in vivo mouse brains showed different time-course variations and residual contrast depending on the irradiation doses. Future studies will focus on validation at long-term time points, including early and late delayed response and evaluation of irradiation effects in various tissue types.

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Fast neutron irradiation deteriorates hippocampus-related memory ability in adult mice

Cited by 16 publications

References 17 publications

Modeling Heavy-Ion Impairment of Hippocampal Neurogenesis after Acute and Fractionated Irradiation

Modeling Heavy-Ion Impairment of Hippocampal Neurogenesis after Acute and Fractionated Irradiation

X Irradiation Induces Acute Cognitive Decline via Transient Synaptic Dysfunction

Image-Based Evaluation of Irradiation Effects in Brain Tissues by Measuring Absolute Electrical Conductivity Using MRI

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