scholarly journals Long-Term Changes in Cognition and Physiology after Low-Dose 16O Irradiation

2019 ◽  
Vol 20 (1) ◽  
pp. 188 ◽  
Author(s):  
Alexis Howe ◽  
Frederico Kiffer ◽  
Tyler C. Alexander ◽  
Vijayalakshmi Sridharan ◽  
Jing Wang ◽  
...  

Astronauts traveling to Mars will be exposed to high levels of ionizing radiation upon leaving low-Earth orbit. During prolonged space travel, astronauts are exposed to galactic cosmic rays (GCRs) composed of protons; oxygen molecules; and high energy, high mass charged particles. Notably, oxygen molecules can travel through the shielding of spacecraft, potentially impacting 25% of the hippocampus. The aim of the current study was to assess whether 16O-particle radiation induced a behavioral deficit and histological changes in mice. Mice were sent to the National Aeronautics and Space Administration (NASA) Space Radiation Laboratory at Brookhaven National Laboratory and exposed to particulate 16O radiation at doses of 0 and 0.05 Gy. Nine months after irradiation, the mice were tested for novel object recognition and in the Y-maze, after which the animals were sacrificed. The brains were then dissected along the midsagittal plane for Golgi staining. Exposure to 0.05 Gy significantly impaired novel object recognition. However, short term memory and exploratory activity in the Y-maze were not affected. Micromorphometric analysis revealed significant decreases in mushroom spine density in the dentate gyrus and cornu Ammonis-1 and -3 of the hippocampus. Sholl analysis revealed a significant decrease in dendritic complexity in the dentate gyrus. The present data provide evidence that space radiation has deleterious effects on mature neurons associated with hippocampal learning and memory.

2021 ◽  
Vol 4 (3) ◽  
pp. 36-50
Author(s):  
Yusuf Yusha'u ◽  
Umar Muhammad Adam ◽  
Alhassan Abdul Wahab ◽  
Malajiya Ibrahim Alhaji Saleh ◽  
Jamilu Ya’u

Depression affects over 264 million people of all ages globally. Major depressive disorder significantly and chronically reduced quality of life by its association with functional impairment both at home and in the workplace. Depressive patients consistently complain about cognitive disturbances, significantly exacerbating the burden of this illness. Several studies have shown that alpha-lipoic acid (ALA) possesses mitochondrial, antioxidant, anti-inflammatory and anti-diabetic properties, indicating a basis for evaluating the efficacy of ALA in depression. Hence, this research aimed to assess the possible anti-depressant effect of ALA in mice exposed to the open space forced swim test (OSFST) model of depression. Twenty-five (25) Swiss albino mice were grouped into five groups (n=5). Group 1: [Normal saline (NS)], Groups 2, 3 and 4 received graded doses of ALA 100, 200 and 400 mg/kg, respectively, Group 5 received fluoxetine 20 mg/kg orally. The animals were subjected to OSFST, novel object recognition test (NORT) and Y-maze test. Serotonin, brain-derived neurotrophic factor (BDNF), superoxide dismutase (SOD), malondialdehyde (MDA) and catalase levels of the mice were assessed. Treatment with ALA and fluoxetine significantly decreased immobility time compared to NS group in OSFST (p<0.05). Also, ALA at doses of 200 & 400 mg/kg and fluoxetine 20 mg/kg significantly increased spontaneous alternation ratio in the Y-maze test compared to the normal saline group (p<0.05), however, no significant difference was observed in novel object recognition using NORT between NS, ALA and fluoxetine treated groups. Similarly, the level of serotonin, SOD and catalase were not altered between the ALA and fluoxetine treated groups and NS group. In contrast, fluoxetine 20 mg/kg increased the brain BDNF level of the mice (p<0.05). Alpha-lipoic acid ameliorated depression in the OSFST murine model of depression and improved their cognition. Thus ALA can be a promising candidate in the development of novel anti-depressant medication.


2015 ◽  
Vol 308 (5) ◽  
pp. L416-L428 ◽  
Author(s):  
Melpo Christofidou-Solomidou ◽  
Ralph A. Pietrofesa ◽  
Evguenia Arguiri ◽  
Kelly S. Schweitzer ◽  
Evgeny V. Berdyshev ◽  
...  

Despite considerable progress in identifying health risks to crewmembers related to exposure to galactic/cosmic rays and solar particle events (SPE) during space travel, its long-term effects on the pulmonary system are unknown. We used a murine risk projection model to investigate the impact of exposure to space-relevant radiation (SR) on the lung. C3H mice were exposed to 137Cs gamma rays, protons (acute, low-dose exposure mimicking the 1972 SPE), 600 MeV/u 56Fe ions, or 350 MeV/u 28Si ions at the NASA Space Radiation Laboratory at Brookhaven National Laboratory. Animals were irradiated at the age of 2.5 mo and evaluated 23.5 mo postirradiation, at 26 mo of age. Compared with age-matched nonirradiated mice, SR exposures led to significant air space enlargement and dose-dependent decreased systemic oxygenation levels. These were associated with late mild lung inflammation and prominent cellular injury, with significant oxidative stress and apoptosis (caspase-3 activation) in the lung parenchyma. SR, especially high-energy 56Fe or 28Si ions markedly decreased sphingosine-1-phosphate levels and Akt- and p38 MAPK phosphorylation, depleted anti-senescence sirtuin-1 and increased biochemical markers of autophagy. Exposure to SR caused dose-dependent, pronounced late lung pathological sequelae consistent with alveolar simplification and cellular signaling of increased injury and decreased repair. The associated systemic hypoxemia suggested that this previously uncharacterized space radiation-associated lung injury was functionally significant, indicating that further studies are needed to define the risk and to develop appropriate lung-protective countermeasures for manned deep space missions.


2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Andrew T. Mugwagwa ◽  
Louis L. Gadaga ◽  
William Pote ◽  
Dexter Tagwireyi

Crinum macowanii has been found to contain alkaloids that have activity against acetylcholinesterase enzyme in vitro. The present study was undertaken to investigate the in vivo ability of hydroethanolic crude extract of Crinum macowanii to ameliorate memory impairment induced by scopolamine. Thirty-six male Balb/c mice weighing around 25–35 g were employed in the present investigation. Y-maze and novel object recognition apparatus served as the exteroceptive behavioural models, and scopolamine-induced amnesia served as the interoceptive behavioural model. C. macowanii (10, 20, and 40 mg/kg p.o.) was administered in single doses to the mice. Donepezil (3 mg/kg p.o.) was used as a positive control agent. C. macowanii extract reversed the amnesia induced by scopolamine as indicated by a dose-dependent increase in spontaneous alternation performance in the Y-maze task. C. macowanii 40 mg/kg showed significant activity (p<0.05 versus negative control), comparable to that of the positive control. C. macowanii also showed memory-enhancing activity against scopolamine-induced memory deficits in the long-term memory novel object recognition performance as indicated by a dose-dependent increase in the discrimination index. The results indicate that the hydroethanolic extract of C. macowanii may be a useful memory restorative mediator in the treatment of cognitive disorders such as Alzheimer’s disease.


2021 ◽  
Vol 12 ◽  
Author(s):  
Sydney Weber Boutros ◽  
Benjamin Zimmerman ◽  
Sydney C. Nagy ◽  
Joanne S. Lee ◽  
Ruby Perez ◽  
...  

The deep space environment contains many risks to astronauts during space missions, such as galactic cosmic rays (GCRs) comprised of naturally occurring heavy ions. Heavy ion radiation is increasingly being used in cancer therapy, including novel regimens involving carbon therapy. Previous investigations involving simulated space radiation have indicated a host of detrimental cognitive and behavioral effects. Therefore, there is an increasing need to counteract these deleterious effects of heavy ion radiation. Here, we assessed the ability of amifostine to mitigate cognitive injury induced by simulated GCRs in C57Bl/6J male and female mice. Six-month-old mice received an intraperitoneal injection of saline, 107 mg/kg, or 214 mg/kg of amifostine 1 h prior to exposure to a simplified five-ion radiation (protons, 28Si, 4He, 16O, and 56Fe) at 500 mGy or sham radiation. Mice were behaviorally tested 2–3 months later. Male mice that received saline and radiation exposure failed to show novel object recognition, which was reversed by both doses of amifostine. Conversely, female mice that received saline and radiation exposure displayed intact object recognition, but those that received amifostine prior to radiation did not. Amifostine and radiation also had distinct effects on males and females in the open field, with amifostine affecting distance moved over time in both sexes, and radiation affecting time spent in the center in females only. Whole-brain analysis of cFos immunoreactivity in male mice indicated that amifostine and radiation altered regional connectivity in areas involved in novel object recognition. These data support that amifostine has potential as a countermeasure against cognitive injury following proton and heavy ion irradiation in males.


2019 ◽  
Vol 35 (1) ◽  
Author(s):  
Hyun Jung Kwon ◽  
Woosuk Kim ◽  
Hyo Young Jung ◽  
Min Soo Kang ◽  
Jong Whi Kim ◽  
...  

Abstract In the present study, we investigated the effects of heat shock protein 70 (HSP70) on novel object recognition, cell proliferation, and neuroblast differentiation in the hippocampus. To facilitate penetration into the blood–brain barrier and neuronal plasma membrane, we created a Tat-HSP70 fusion protein. Eight-week-old mice received intraperitoneal injections of vehicle (10% glycerol), control-HSP70, or Tat-HSP70 protein once a day for 21 days. To elucidate the delivery efficiency of HSP70 into the hippocampus, western blot analysis for polyhistidine was conducted. Polyhistidine protein levels were significantly increased in control-HSP70- and Tat-HSP70-treated groups compared to the control or vehicle-treated group. However, polyhistidine protein levels were significantly higher in the Tat-HSP70-treated group compared to that in the control-HSP70-treated group. In addition, immunohistochemical study for HSP70 showed direct evidences for induction of HSP70 immunoreactivity in the control-HSP70- and Tat-HSP70-treated groups. Administration of Tat-HSP70 increased the novel object recognition memory compared to untreated mice or mice treated with the vehicle. In addition, the administration of Tat-HSP70 significantly increased the populations of proliferating cells and differentiated neuroblasts in the dentate gyrus compared to those in the control or vehicle-treated group based on the Ki67 and doublecortin (DCX) immunostaining. Furthermore, the phosphorylation of cAMP response element-binding protein (pCREB) was significantly enhanced in the dentate gyrus of the Tat-HSP70-treated group compared to that in the control or vehicle-treated group. Western blot study also demonstrated the increases of DCX and pCREB protein levels in the Tat-HSP70-treated group compared to that in the control or vehicle-treated group. In contrast, administration of control-HSP70 moderately increased the novel object recognition memory, cell proliferation, and neuroblast differentiation in the dentate gyrus compared to that in the control or vehicle-treated group. These results suggest that Tat-HSP70 promoted hippocampal functions by increasing the pCREB in the hippocampus.


2021 ◽  
Author(s):  
Ivonne Becker ◽  
Lihua Wang‐Eckhardt ◽  
Julia Lodder‐Gadaczek ◽  
Yong Wang ◽  
Agathe Grünewald ◽  
...  

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