Sleep Behavior and EEG Oscillations in Aged Dp(16)1Yey/+ Mice: A Down Syndrome Model

Levenga, Josien; Peterson, Daniel J.; Cain, Patricia A.; Hoeffer, Charles A.

doi:10.1016/j.neuroscience.2018.02.009

Cited by 14 publications

(15 citation statements)

References 36 publications

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“…Previous studies that have interrogated hippocampal function in similar mutant mouse populations (Aziz et al, 2018;Levenga et al, 2018) have found no impairments of mnemonic function in Dp10Yey mice (Belichenko et al, 2015;Yu et al, 2010b). In contrast, we observed decreased alternation rates in Dp10Yey mice suggestive of a spatial working memory deficit (Deacon and Rawlins, 2006).…”

Section: Discussioncontrasting

confidence: 61%

Altered Hippocampal-Prefrontal Neural Dynamics in Mouse Models of Down Syndrome

et al. 2020

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Graphical Abstract Highlights d Study of behavior and EEG in three partially trisomic mouse models of Down syndrome (DS) d These mutant mice show non-overlapping differences in spatial working memory function d Behavioral changes segregate with distinct EEG abnormalities in the hippocampus and mPFC d This links cognitive deficits to specific changes in hippocampal and mPFC circuit dynamics SUMMARYAltered neural dynamics in the medial prefrontal cortex (mPFC) and hippocampus may contribute to cognitive impairments in the complex chromosomal disorder Down syndrome (DS). Here, we demonstrate non-overlapping behavioral differences associated with distinct abnormalities in hippocampal and mPFC electrophysiology during a canonical spatial working memory task in three partially trisomic mouse models of DS (Dp1Tyb, Dp10Yey, and Dp17Yey) that together cover all regions of homology with human chromosome 21 (Hsa21). Dp1Tyb mice show slower decision-making (unrelated to the gene dose of DYRK1A, which has been implicated in DS cognitive dysfunction) and altered theta dynamics (reduced frequency, increased hippocampal-mPFC coherence, and increased modulation of hippocampal high gamma); Dp10Yey mice show impaired alternation performance and reduced theta modulation of hippocampal low gamma; and Dp17Yey mice are not significantly different from the wild type. These results link specific hippocampal and mPFC circuit dysfunctions to cognitive deficits in DS models and, importantly, map them to discrete regions of Hsa21.

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Section: Discussioncontrasting

confidence: 61%

Altered Hippocampal-Prefrontal Neural Dynamics in Mouse Models of Down Syndrome

et al. 2020

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“…This finding is consistent with previous reports of impairment of Dp16 mice in other tasks that require hippocampal function, e.g., Morris Water Maze and Contextual Fear Conditioning, and of hippocampal learning deficits in other mouse models of DS, including Ts65Dn and Ts1Cje mice, each of which is trisomic for a subset of the genes that are trisomic in the Dp16 mice (56,61,(64)(65)(66)(67). This finding is also consistent with previous studies that showed that Dp16 mice display abnormal hippocampus-based long-term potentiation (LTP) (60,61,67,68).…”

Section: Discussionsupporting

confidence: 90%

Pro-inflammatory Cytokine GM-CSF Improves Learning/Memory and Brain Pathology in Dp16 Down Syndrome Mice and Improves Learning/Memory in Wild-Type Mice

Ahmed

Wang

Elos

et al. 2021

Preprint

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Down syndrome (DS) is characterized by chronic neuroinflammation, peripheral inflammation, astrogliosis, imbalanced excitatory/inhibitory neuronal function, and cognitive deficits in both humans and mouse models. Suppression of inflammation has been proposed as a therapeutic approach to treating DS co-morbidities, including intellectual disability (DS/ID). Conversely, we discovered previously that treatment with the pro-inflammatory cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) improved cognition and reduced biomarkers of brain pathology in humans with Alzheimer·s disease (AD), another inflammatory disorder, and in a mouse model of AD. To investigate the effects of GM-CSF treatment on DS/ID, we assessed behavior and brain pathology in 12-14 month-old DS mice (Dp[16]1Yey) and their wild-type (WT) littermates, neither of which develop amyloid, and found that GM-CSF treatment improved performance in the radial arm water maze in both Dp16 and WT mice compared to placebo. Dp16 mice also showed abnormal astrocyte morphology and aggregation and fewer calretinin-positive interneurons, both of which were improved by GM-CSF treatment. These findings suggest that stimulating and/or modulating inflammation and the innate immune system with GM-CSF treatment may enhance cognition in both people with DS/ID and in the typical aging population.

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“…The sleep phenotype of Ts65Dn and Ts1Cje mice carrying one extra copy of partially overlapping segments of mouse chromosome 16, was reported in our previous study in which Ts65Dn mice showed increased waking amounts at the expense of non-REM sleep though Ts1Cje mice had no sleep or EEG abnormalities 40 . Recently, it was reported that aged Dp16 mice spend more time awake with the frequent transition from sleep to wakefulness www.nature.com/scientificreports/ and decreased delta power during non-REM sleep, similarly in sleep phenotype to Ts65Dn mice 41 . Although the occurrence of OSA has not been explored in these models so far, these findings are consistent with sleep disturbances found in individuals with DS.…”

Section: Discussionmentioning

confidence: 99%

Detailed evaluation of the upper airway in the Dp(16)1Yey mouse model of Down syndrome

Takahashi

Sakai

Iwasaki

et al. 2020

Sci Rep

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A high prevalence of obstructive sleep apnea (OSA) has been reported in Down syndrome (DS) owing to the coexistence of multiple predisposing factors related to its genetic abnormality, posing a challenge for the management of OSA. We hypothesized that DS mice recapitulate craniofacial abnormalities and upper airway obstruction of human DS and can serve as an experimental platform for OSA research. This study, thus, aimed to quantitatively characterize the upper airway as well as craniofacial abnormalities in Dp(16)1Yey (Dp16) mice. Dp16 mice demonstrated craniofacial hypoplasia, especially in the ventral part of the skull and the mandible, and rostrally positioned hyoid. These changes were accompanied with a shorter length and smaller cross-sectional area of the upper airway, resulting in a significantly reduced upper airway volume in Dp16 mice. Our non-invasive approach, a combination of computational fluid dynamics and high-resolution micro-CT imaging, revealed a higher negative pressure inside the airway of Dp16 mice compared to wild-type littermates, showing the potential risk of upper airway collapse. Our study indicated that Dp16 mice can be a useful model to examine the pathophysiology of increased upper airway collapsibility of DS and to evaluate the efficacy of therapeutic interventions for breathing and sleep anomalies.

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Sleep Behavior and EEG Oscillations in Aged Dp(16)1Yey/+ Mice: A Down Syndrome Model

Cited by 14 publications

References 36 publications

Altered Hippocampal-Prefrontal Neural Dynamics in Mouse Models of Down Syndrome

Altered Hippocampal-Prefrontal Neural Dynamics in Mouse Models of Down Syndrome

Pro-inflammatory Cytokine GM-CSF Improves Learning/Memory and Brain Pathology in Dp16 Down Syndrome Mice and Improves Learning/Memory in Wild-Type Mice

Detailed evaluation of the upper airway in the Dp(16)1Yey mouse model of Down syndrome

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