scholarly journals Meta-analysis of Cognitive Performance by Novel Object Recognition after Proton and Heavy Ion Exposures

2019 ◽  
Vol 192 (5) ◽  
pp. 463 ◽  
Author(s):  
Eliedonna Cacao ◽  
Francis A. Cucinotta
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.


2020 ◽  
Author(s):  
Regan Fry ◽  
Jeremy Bennet Wilmer ◽  
Isabella Xie ◽  
Mieke Verfaellie ◽  
Joseph DeGutis

The question of the face specificity of recognition deficits in prosopagnosia is fundamental to the organization of high-level visual processing and memory and has been vigorously debated numerous times over the last 20 years. This debate was recently revived in developmental prosopagnosics (DPs) by a meta-analysis reporting that a large percentage of DPs (ranging from 22-80%) have mild to major object recognition deficits (Geskin & Behrmann, 2017). Subsequent studies have also shown significantly lower DP group-level object recognition performance. However, previous investigations measuring object recognition have largely used familiar objects (e.g., cars) where performance may depend on object-specific experience, leaving the question open as to whether DPs would perform similarly when the stimuli are completely unfamiliar objects. To investigate this, in the current study we tested 30 DPs and 30 matched controls on a novel object memory test (NOMT Ziggerins) and the Cambridge Face Memory Test (CFMT). DPs were impaired on the CFMT but performed similarly to controls on the NOMT. We also compared DP NOMT performance to a larger matched sample of 274 web-based controls and found no difference in accuracy or reaction time. Individual analyses demonstrated that only one DP reached major impairment in object recognition on the NOMT, an impairment rate no different from that in either control group. Together, these results demonstrate essentially normal object recognition in DPs for a class of novel objects that serves as a powerful index for broader novel object recognition capacity. These results raise the possibility that DPs do not have object recognition deficits per se, but rather may have a decreased capacity to benefit from their experience with highly familiar object categories.


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

2021 ◽  
Vol 15 ◽  
Author(s):  
Cesar Sierra ◽  
Ilario De Toma ◽  
Lorenzo Lo Cascio ◽  
Esteban Vegas ◽  
Mara Dierssen

The use of mouse models has revolutionized the field of Down syndrome (DS), increasing our knowledge about neuropathology and helping to propose new therapies for cognitive impairment. However, concerns about the reproducibility of results in mice and their translatability to humans have become a major issue, and controlling for moderators of behavior is essential. Social and environmental factors, the experience of the researcher, and the sex and strain of the animals can all have effects on behavior, and their impact on DS mouse models has not been explored. Here we analyzed the influence of a number of social and environmental factors, usually not taken into consideration, on the behavior of male and female wild-type and trisomic mice (the Ts65Dn model) in one of the most used tests for proving drug effects on memory, the novel object recognition (NOR) test. Using principal component analysis and correlation matrices, we show that the ratio of trisomic mice in the cage, the experience of the experimenter, and the timing of the test have a differential impact on male and female and on wild-type and trisomic behavior. We conclude that although the NOR test is quite robust and less susceptible to environmental influences than expected, to obtain useful results, the phenotype expression must be contrasted against the influences of social and environmental factors.


2018 ◽  
Author(s):  
Damien Marechal ◽  
Véronique Brault ◽  
Alice Leon ◽  
Dehren Martin ◽  
Patricia Lopes Pereira ◽  
...  

ABSTRACTIdentifying dosage sensitive genes is a key to understand the mechanisms underlying intellectual disability in Down syndrome (DS). The Dp(17Abcg1-Cbs)1Yah DS mouse model (Dp1Yah) show cognitive phenotype and needs to be investigated to identify the main genetic driver. Here, we report that, in the Dp1Yah mice, 3 copies of the Cystathionine-beta-synthase gene (Cbs)are necessary to observe a deficit in the novel object recognition (NOR) paradigm. Moreover, the overexpression ofCbsalone is sufficient to induce NOR deficit. Accordingly targeting the overexpression of human CBS, specifically in Camk2a-expressing neurons, leads to impaired objects discrimination. Altogether this shows thatCbsoverdosage is involved in DS learning and memory phenotypes. In order to go further, we identified compounds that interfere with the phenotypical consequence of CBS overdosage in yeast. Pharmacological intervention in the Tg(CBS) with one selected compound restored memory in the novel object recognition. In addition, using a genetic approach, we demonstrated an epistatic interaction betweenCbsandDyrk1a, another human chromosome 21 gene encoding the dual-specificity tyrosine phosphorylation-regulated kinase 1a and an already known target for DS therapeutic intervention. Further analysis using proteomic approaches highlighted several pathways, including synaptic transmission, cell projection morphogenesis, and actin cytoskeleton, that are affected by DYRK1A and CBS overexpression. Overall we demonstrated that CBS overdosage underpins the DS-related recognition memory deficit and that bothCBSandDYRK1Ainteract to control accurate memory processes in DS. In addition, our study establishes CBS as an intervention point for treating intellectual deficiencies linked to DS.SIGNIFICANT STATEMENTHere, we investigated a region homologous to Hsa21 and located on mouse chromosome 17. We demonstrated using three independent genetic approaches that the overdosage of the Cystathionine-beta-synthase gene (Cbs) gene, encoded in the segment, is necessary and sufficient to induce deficit in novel object recognition (NR).In addition, we identified compounds that interfere with the phenotypical consequence of CBS overdosage in yeast and in mouse transgenic lines. Then we analyzed the relation between Cbs overdosage and the consequence of DYRK1a overexpression, a main driver of another region homologous to Hsa21 and we demonstrated that an epistatic interaction exist betweenCbsandDyrk1aaffecting different pathways, including synaptic transmission, cell projection morphogenesis, and actin cytoskeleton.


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