Cognitive impairments in a Down syndrome model with abnormal hippocampal and prefrontal dynamics and cytoarchitecture

Muza, Phillip; Bush, Daniel; Pérez-González, Marta; Zouhair, Ines; Cleverley, Karen; Aoidi, Rifdat; West, Steven J.; Good, Mark Andrew; Tybulewicz, Victor L. J.; Walker, Matthew; Fisher, Elizabeth; Chang, Pishan

doi:10.1016/j.isci.2023.106073

iScience

2023

DOI: 10.1016/j.isci.2023.106073

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Cognitive impairments in a Down syndrome model with abnormal hippocampal and prefrontal dynamics and cytoarchitecture

Phillip Muza¹,

Daniel Bush²,

Marta Pérez-González³

et al.

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2024

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Cited by 3 publications

References 105 publications

(128 reference statements)

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Selective vulnerability of the ventral hippocampus-prelimbic cortex axis parvalbumin interneuron network underlies learning deficits of fragile X mice

Bhandari,

Kanodia,

Donato

et al. 2024

Cell Reports

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Selective vulnerability of the ventral hippocampus-prelimbic cortex axis parvalbumin interneuron network underlies learning deficits of fragile X mice

Bhandari,

Kanodia,

Donato

et al. 2024

Cell Reports

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Neuronal oscillations in cognition: Down syndrome as a model of mouse to human translation

Chang,

Pérez-González,

Constable

et al. 2024

Neuroscientist

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Down syndrome (DS), a prevalent cognitive disorder resulting from trisomy of human chromosome 21 (Hsa21), poses a significant global health concern. Affecting approximately 1 in 800 live births worldwide, DS is the leading genetic cause of intellectual disability and a major predisposing factor for early-onset Alzheimer’s dementia. The estimated global population of individuals with DS is 6 million, with increasing prevalence due to advances in DS health care. Global efforts are dedicated to unraveling the mechanisms behind the varied clinical outcomes in DS. Recent studies on DS mouse models reveal disrupted neuronal circuits, providing insights into DS pathologies. Yet, translating these findings to humans faces challenges due to limited systematic electrophysiological analyses directly comparing human and mouse. Additionally, disparities in experimental procedures between the two species pose hurdles to successful translation. This review provides a concise overview of neuronal oscillations in human and rodent cognition. Focusing on recent DS mouse model studies, we highlight disruptions in associated brain function. We discuss various electrophysiological paradigms and suggest avenues for exploring molecular dysfunctions contributing to DS-related cognitive impairments. Deciphering neuronal oscillation intricacies holds promise for targeted therapies to alleviate cognitive disabilities in DS individuals.

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The mTOR Pathway: A Common Link Between Alzheimer’s Disease and Down Syndrome

Wohlfert,

Phares,

Granholm

2024

JCM

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Down syndrome (DS) is a chromosomal condition that causes many systemic dysregulations, leading to several possible age-related diseases including Alzheimer’s disease (AD). This may be due to the triplication of the Amyloid precursor protein (APP) gene or other alterations in mechanistic pathways, such as the mTOR pathway. Impairments to upstream regulators of mTOR, such as insulin, PI3K/AKT, AMPK, and amino acid signaling, have been linked to amyloid beta plaques (Aβ) and neurofibrillary tangles (NFT), the most common AD pathologies. However, the mechanisms involved in the progression of pathology in human DS-related AD (DS-AD) are not fully investigated to date. Recent advancements in omics platforms are uncovering new insights into neurodegeneration. Genomics, spatial transcriptomics, proteomics, and metabolomics are novel methodologies that provide more data in greater detail than ever before; however, these methods have not been used to analyze the mTOR pathways in connection to DS-AD. Using these new techniques can unveil unexpected insights into pathological cellular mechanisms through an unbiased approach.

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Cognitive impairments in a Down syndrome model with abnormal hippocampal and prefrontal dynamics and cytoarchitecture

Cited by 3 publications

References 105 publications

Selective vulnerability of the ventral hippocampus-prelimbic cortex axis parvalbumin interneuron network underlies learning deficits of fragile X mice

Selective vulnerability of the ventral hippocampus-prelimbic cortex axis parvalbumin interneuron network underlies learning deficits of fragile X mice

Neuronal oscillations in cognition: Down syndrome as a model of mouse to human translation

The mTOR Pathway: A Common Link Between Alzheimer’s Disease and Down Syndrome

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