Transient Impairment of Hippocampus-dependent Learning and Memory in Relatively Low-Dose of Acute Radiation Syndrome is Associated with Inhibition of Hippocampal Neurogenesis

Abstract

Neurogenesis in the adult hippocampus, which occurs constitutively, is vulnerable to ionizing radiation. In the relatively low-dose exposure of acute radiation syndrome (ARS), the change in the adult hippocampal function is poorly understood. This study analyzed the changes in apoptotic cell death and neurogenesis in the DGs of hippocampi from adult ICR mice with single whole-body gamma-irradiation using the TUNEL method and immunohistochemical markers of neurogenesis, Ki-67 and doublecortin (DCX). In addition, the hippocampus-dependent learning and memory tasks after single whole-body gamma-irradiation were examined in order to evaluate the hippocampus-related behavioral dysfunction in the relatively low-dose exposure of ARS. The number of TUNEL-positive apoptotic nuclei in the dentate gyrus (DG) was increased 6-12 h after acute gamma-irradiation (a single dose of 0.5 to 4 Gy). In contrast, the number of Ki-67- and DCX-positive cells began to decrease significantly 6 h postirradiation, reaching its lowest level 24 h after irradiation. The level of Ki-67 and DCX immunoreactivity decreased in a dose-dependent manner within the range of irradiation applied (0-4 Gy). In passive avoidance and object recognition memory test, the mice trained 1 day after acute irradiation (2 Gy) showed significant memory deficits, compared with the sham controls. In conclusion, the pattern of the hippocampus-dependent memory dysfunction is consistent with the change in neurogenesis after acute irradiation. It is suggested that a relatively low dose of ARS in adult ICR mice is sufficiently detrimental to interrupt the functioning of the hippocampus, including learning and memory, possibly through the inhibition of neurogenesis.

Neuroprotective effect of acute melatonin treatment on hippocampal neurons against irradiation by inhibition of caspase-3

“…The hippocampus is a region of active proliferation and neurogenesis within the brain. It has previously been demonstrated that ionizing radiation induces the apoptosis of neural cells within the subventricular zone of the lateral ventricles and the subgranular zone of the hippocampus in the adult brain (23). Furthermore, previous studies have demonstrated that the caspase-dependent cytotoxicity of ionizing radiation in hippocampal neurons is induced by oxidative stress (24,25).…”

Once the Light Touch to the Brain: Cytotoxic Effects of Low-Dose Gamma-Ray, Laser Light, and Visible Light on Rat Neuronal Cell Culture

“…In the literature, numerous studies showed cytotoxicity of radiation at cellular level [10,11,[26][27][28][29][30][31][32]. Yang et al [10] reported that gamma-ray (0-4 Gy for 12 hours) cause CASPACE dependent cytotoxicity through oxidative stress on immature rat hippocampal neuronal cell culture.…”

“…Michelin et al [30] also confirmed that CASPACE 3 enzyme plays role in gamma-ray induced neuron death and apoptosis. Kim et al [28] revealed apoptosis in hippocampal neurons after 6 hours-14 days of whole body gamm-rays (0-4 Gy) irradiation of the mice. Furthermore, Moore et al [31] have been put forward that irradiation of the cerebral tissue of mice causes disruption o blood-brain barrier, secretion of inflammatory cytokines, vascular collapse and consequently cerebral edema via cyclooxygenase-2 enzyme in long-term.…”

Gamma-Ray Susceptibility of Immature and Mature Hippocampal Cultured Cells

“…Exposure of mammalian brains to ionizing radiation induces apoptosis of neural immature progenitor cells in the subventricular zone of the lateral ventricles and in the subgranular zone of the hippocampal dentate gyrus [3,4,10,12,17]. The phenomenon in adult mouse hippocampus may lead to hippocampal-dependent learning and memory impairment [10], although there is no radiation-induced apoptotic appearance in other hippocampal regions, including cornu ammonis (CA) 1 and CA3.…”

“…The phenomenon in adult mouse hippocampus may lead to hippocampal-dependent learning and memory impairment [10], although there is no radiation-induced apoptotic appearance in other hippocampal regions, including cornu ammonis (CA) 1 and CA3. Therefore, it is important to clarify the degree of radiosensitivity in the stages of neural development at which they are most vulnerable.…”