Ionizing radiation impairs the formation of trace fear memories and reduces hippocampal neurogenesis.

Achanta, Pragathi; Fuß, Martin; Martinez, Joe L.

doi:10.1037/a0016870

Cited by 51 publications

(50 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We found no statistical difference in the number of proliferating cells from 72 h to 1 month postradiation, suggesting that cognitive decline continues while the cell numbers remain relatively unchanged. We, and others, speculate that the profound cognitive dysfunction seen with radiation exposure in younger children can be attributed to the significantly higher levels of cell proliferation and neurogenesis within the immature nervous system as compared to older individuals [16,43].…”

Section: Discussionmentioning

confidence: 94%

Therapeutic doses of cranial irradiation induce hippocampus-dependent cognitive deficits in young mice

et al. 2011

View full text Add to dashboard Cite

Fractionated cranial irradiation is an essential part of treatment in the management of cohorts of pediatric brain tumor and leukemia patients. Ionizing radiation damages normal brain parenchyma through a variety of poorly understood mechanisms and results in cognitive dysfunction and significant life-long disability. The goal of our study was to establish and characterize a mouse model of radiation-induced damage to the developing nervous system. Male C57BL/6 mice were exposed to a total dose of 20 Gy of fractionated cranial irradiation at 1 month of age to assess the early and late effects of clinically relevant irradiation doses on the young mouse brain. Compared to age-matched controls, an acute and prolonged decrease in proliferation and the number of immature neurons in the stem cell niche of the hippocampal subgranular zone within the dentate gyrus at 72 h and 1 month following cranial irradiation was noted. Behavioral characterization at 1 and 5 months post-radiation demonstrated significant, persistent and progressive hippocampus-dependent learning deficits. Our study characterizes a clinically relevant mouse model of radiation-induced damage that serves as a platform for future evaluation of therapeutic interventions that may mitigate such cognitive damage. Our research also emphasizes the need for targeted treatment strategies that protect regions of neurogenesis while maximizing therapeutic effects in pediatric cancer patients.

show abstract

Section: Discussionmentioning

confidence: 94%

Therapeutic doses of cranial irradiation induce hippocampus-dependent cognitive deficits in young mice

et al. 2011

View full text Add to dashboard Cite

show abstract

“…Hippocampal-dependent learning and memory are strongly influenced by the activity of neural stem cells and their proliferative progeny (31). Increased neurogenesis may result in improved performance in hippocampal-dependent memory tasks (32), while disruption of hippocampal neurogenesis can result in decreased performance in hippocampal-dependent tasks (33). Given our own data, along with those from others, we felt it was possible that changes in neurogenesis might play an important role in the behavioral consequence of RCI.…”

Section: Discussionmentioning

confidence: 99%

Delayed Administration of Alpha-Difluoromethylornithine Prevents Hippocampus-Dependent Cognitive Impairment after Single and Combined Injury in Mice

et al. 2014

View full text Add to dashboard Cite

Radiation exposure due to radiological terrorism and military circumstances are a continuing threat for the civilian population. In an uncontrolled radiation event, it is likely that there will be other types of injury involved, including trauma. While radiation combined injury is recognized as an area of great significance, overall there is a paucity of information regarding the mechanisms underlying the interactions between irradiation and other forms of injury, or what countermeasures might be effective in ameliorating such changes. The objective of this study was to determine if difluoromethylornithine (DFMO) could reduce the adverse effects of single or combined injury if administered beginning 24 h after exposure. Eight-week-old C57BL/J6 young-adult male mice received whole-body cesium-137 (137Cs) irradiation with 4 Gy. Immediately after irradiation, unilateral traumatic brain injury was induced using a controlled cortical impact system. Forty-four days postirradiation, animals were tested for hippocampus-dependent cognitive performance in the Morris water maze. After cognitive testing, animals were euthanized and their brains snap frozen for immunohisto-chemical assessment of neuroinflammation (activated microglia) and neurogenesis in the hippocampal dentate gyrus. Our data show that single and combined injuries induced variable degrees of hippocampus-dependent cognitive dysfunction, and when given 24 h post trauma, DFMO treatment ameliorated those effects. Cellular changes including neuro-genesis and numbers of activated microglia were generally not associated with the cognitive changes. Further analyses also revealed that DFMO increased hippocampal protein levels of the antioxidants thioredoxin 1 and peroxiredoxin 3 compared to vehicle treated animals. While the mechanisms responsible for the improvement in cognition after DFMO treatment are not yet clear, these results constitute a basis for further development of DFMO as a countermeasure for ameliorating the of risks for cognitive dysfunction in individuals subjected to trauma and radiation combined injury.

show abstract

“…There is compelling evidence that radiation leads to significant impairments in both neurogenesis and angiogenesis [19, 90-93, 95, 96]. Interestingly, both chronic [111, 112] and intermittent [113] systemic hypoxia stimulate these processes.…”

Section: Radiation-induced Changes In the Neurovascular Unitmentioning

confidence: 99%

Whole Brain Radiation-Induced Vascular Cognitive Impairment: Mechanisms and Implications

Warrington

Ashpole

Csiszár³

et al. 2013

J Vasc Res

View full text Add to dashboard Cite

Mild cognitive impairment is a well-documented consequence of whole brain radiation therapy (WBRT) that affects 40-50% of long-term brain tumor survivors. The exact mechanisms for the decline in cognitive function after WBRT remain elusive and no treatment or preventative measures are available for use in the clinic. Here, we review recent findings indicating how changes in the neurovascular unit may contribute to the impairments in learning and memory. In addition to affecting neuronal development, WBRT induces profound capillary rarefaction within the hippocampus - a region of the brain important for learning and memory. Therapeutic strategies such as hypoxia, which restore the capillary density, result in the rescue of cognitive function. In addition to decreasing vascular density, WBRT impairs vasculogenesis and/or angiogenesis, which may also contribute to radiation-induced cognitive decline. Further studies aimed at uncovering the specific mechanisms underlying these WBRT-induced changes in the cerebrovasculature are essential for developing therapies to mitigate the deleterious effects of WBRT on cognitive function.

show abstract

Ionizing radiation impairs the formation of trace fear memories and reduces hippocampal neurogenesis.

Cited by 51 publications

References 48 publications

Therapeutic doses of cranial irradiation induce hippocampus-dependent cognitive deficits in young mice

Therapeutic doses of cranial irradiation induce hippocampus-dependent cognitive deficits in young mice

Delayed Administration of Alpha-Difluoromethylornithine Prevents Hippocampus-Dependent Cognitive Impairment after Single and Combined Injury in Mice

Whole Brain Radiation-Induced Vascular Cognitive Impairment: Mechanisms and Implications

Contact Info

Product

Resources

About