Impairment of synaptic plasticity and novel object recognition in the hypergravity-exposed rats

Lee, Jinho; Jang, Doohyeong; Jeong, Hyerin; Kim, Kyu-sung; Yang, Sunggu

doi:10.1038/s41598-020-72639-7

Cited by 4 publications

(4 citation statements)

References 78 publications

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“…23 A 4 g hypergravity condition for 4 weeks could impair synaptic efficacy and long-term potentiation in CA1 neurons of the hippocampus along with the poor performance of a novel object recognition task. 24 A 2 g hypergravity condition during preweaning specifically suppressed vestibular-related stress responses. 25 In this study, our results showed that 7.0-33.0 T SMF exposure for 1 h did not have severe impacts on food and water consumption, body and organ weight, blood composition and chemistry, or histomorphology of the major organs in mice.…”

Section: Discussionmentioning

confidence: 91%

“…Simulated microgravity also delayed ossification manifests during zebrafish development 23 . A 4 g hypergravity condition for 4 weeks could impair synaptic efficacy and long‐term potentiation in CA1 neurons of the hippocampus along with the poor performance of a novel object recognition task 24 . A 2 g hypergravity condition during preweaning specifically suppressed vestibular‐related stress responses 25 …”

Section: Discussionmentioning

confidence: 99%

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Safety evaluation of mice exposed to 7.0–33.0 T high‐static magnetic fields

Tian

Yang

et al. 2020

Magnetic Resonance Imaging

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Magnetic resonance imaging (MRI) of 7 T and higher can provide superior image resolution and capability. Clinical tests have been performed in 9.4 T MRI, and 21.1 T small‐bore‐size MRI has also been tested in rodents. Although the safety issue is a prerequisite for their future medical application, there are very few relevant studies for the safety of static magnetic fields (SMFs) of ≧20 T. The aim of this study was to assess the biological effects of 7.0–33.0 T SMFs in healthy adult mice. This was a prospective study, in which 104 healthy adult C57BL/6 mice were divided into control, sham control, and 7.0–33.0 T SMF‐exposed groups.The sham control group and SMF group were handled identically, except for the electric current for producing SMF. A separate control group was placed outside the magnet and their data were used as normal range. After 1 h exposure, all mice were routinely fed for another 2 months while their body weight and food/water consumption were monitored. After 2 months, their complete blood count, blood biochemistry, key organ weight, and histomorphology were examined. All data are normally distributed. Differences between the sham and SMF‐exposed groups were evaluated by unpaired t test. Most indicators did not show statistically significant changes or were still within the normal ranges, with only a few exceptions. For example, mono % in Group 2 (11.1 T) is 6.03 ± 1.43% while the normal range is 6.60–9.90% (p < 0.05). The cholesterol level in 33 T group is 3.38 ± 0.36 mmol/L while the normal range is 2.48–3.29 mmol/L (p < 0.05). The high‐density lipoprotein cholesterol level in 33 T group is 2.54 ± 0.29 mmol/L while the normal reference range is 1.89–2.43 mmol/L (p < 0.01). Exposure to 7.0–33.0 T for 1 h did not have detrimental effects on normal adult mice. Level of Evidence 1 Technical Efficacy Stage 1

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Safety evaluation of mice exposed to 7.0–33.0 T high‐static magnetic fields

Tian

Yang

et al. 2020

Magnetic Resonance Imaging

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“…A major advantage of the task is that it can be used in both rats and mice (Agarwal et al, 2020;Chang et al, 2020). Current iterations of the NOR paradigm are widely used to study memory (Cole et al, 2020), synaptic plasticity (Lee et al, 2020), impairment and/or recovery of function in brain disease (Grayson et al, 2015), TBI (Amoros-Aguilar et al, 2020), stress (Brivio et al, 2020;Glushchak et al, 2021), aging (Amirazodi et al, 2020), sleep (Shahveisi et al, 2020), autism (Batista et al, 2019;Gandhi and Lee, 2020), and epigenetics (Ellis et al, 2020;Sadat-Shirazi et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

A Sensitive Homecage-Based Novel Object Recognition Task for Rodents

Wooden

Spinetta

Nguyen

et al. 2021

Front. Behav. Neurosci.

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The recognition of novel objects is a common cognitive test for rodents, but current paradigms have limitations, such as low sensitivity, possible odor confounds and stress due to being performed outside of the homecage. We have developed a paradigm that takes place in the homecage and utilizes four stimuli per trial, to increase sensitivity. Odor confounds are eliminated because stimuli consist of inexpensive, machined wooden beads purchased in bulk, so each experimental animal has its own set of stimuli. This paradigm consists of three steps. In Step 1, the sampling phase, animals freely explore familiar objects (FO). Novel Objects (NO1 and NO2) are soiled with bedding from the homecage, to acquire odor cues identical to those of the FO. Steps 2 and 3 are test phases. Herein we report results of this paradigm from neurologically intact adult rats and mice of both sexes. Identical procedures were used for both species, except that the stimuli used for the mice were smaller. As expected in Step 2 (NO1 test phase), male and female rats and mice explored NO1 significantly more than FO. In Step 3 (NO2 test phase), rats of both sexes demonstrated a preference for NO2, while this was seen only in female mice. These results indicate robust novelty recognition during Steps 2 and 3 in rats. In mice, this was reliably seen only in Step 2, indicating that Step 3 was difficult for them under the given parameters. This paradigm provides flexibility in that length of the sampling phase, and the delay between test and sampling phases can be adjusted, to tailor task difficulty to the model being tested. In sum, this novel object recognition test is simple to perform, requires no expensive supplies or equipment, is conducted in the homecage (reducing stress), eliminates odor confounds, utilizes 4 stimuli to increase sensitivity, can be performed in both rats and mice, and is highly flexible, as sampling phase and the delay between steps can be adjusted to tailor task difficulty. Collectively, these results indicate that this paradigm can be used to quantify novel object recognition across sex and species.

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“…It is noticeable that the effects of centrifugation are only partially described in humans [18][19][20][21][22]. Like during microgravity exposure, hypergravity exposure, from 1.5 to 5 g, affects the vestibular functions [23][24][25][26] and modifies gene expression in the brain [27][28][29] and cognitive performances [30][31][32]. The use of hypergravity by centrifugation is required to qualify the biological effects of space motion sickness.…”

Section: Introductionmentioning

confidence: 99%

Hypergravity Increases Blood–Brain Barrier Permeability to Fluorescent Dextran and Antisense Oligonucleotide in Mice

Dubayle

Vanden‐Bossche

Peixoto

et al. 2023

Cells

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The earliest effect of spaceflight is an alteration in vestibular function due to microgravity. Hypergravity exposure induced by centrifugation is also able to provoke motion sickness. The blood–brain barrier (BBB) is the crucial interface between the vascular system and the brain to ensure efficient neuronal activity. We developed experimental protocols of hypergravity on C57Bl/6JRJ mice to induce motion sickness and reveal its effects on the BBB. Mice were centrifuged at 2× g for 24 h. Fluorescent dextrans with different sizes (40, 70 and 150 kDa) and fluorescent antisense oligonucleotides (AS) were injected into mice retro-orbitally. The presence of fluorescent molecules was revealed by epifluorescence and confocal microscopies in brain slices. Gene expression was evaluated by RT-qPCR from brain extracts. Only the 70 kDa dextran and AS were detected in the parenchyma of several brain regions, suggesting an alteration in the BBB. Moreover, Ctnnd1, Gja4 and Actn1 were upregulated, whereas Jup, Tjp2, Gja1, Actn2, Actn4, Cdh2 and Ocln genes were downregulated, specifically suggesting a dysregulation in the tight junctions of endothelial cells forming the BBB. Our results confirm the alteration in the BBB after a short period of hypergravity exposure.

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Impairment of synaptic plasticity and novel object recognition in the hypergravity-exposed rats

Cited by 4 publications

References 78 publications

Safety evaluation of mice exposed to 7.0–33.0 T high‐static magnetic fields

Safety evaluation of mice exposed to 7.0–33.0 T high‐static magnetic fields

A Sensitive Homecage-Based Novel Object Recognition Task for Rodents

Hypergravity Increases Blood–Brain Barrier Permeability to Fluorescent Dextran and Antisense Oligonucleotide in Mice

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