Trisomy of the G protein-coupled K+ channel gene, Kcnj6, affects reward mechanisms, cognitive functions, and synaptic plasticity in mice.
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The findings suggest that triplication of Kcnj6 gene may play an active role in some of the abnormal neurological phenotypes found in Down syndrome.Abstract:
G protein-activated inwardly rectifying K+ channels (GIRK) generate slow inhibitory postsynaptic potentials in the brain via Gi/o protein-coupled receptors. GIRK2, a GIRK subunit, is widely abundant in the brain and has been implicated in various functions and pathologies, such as learning and memory, reward, motor coordination, and Down syndrome. Down syndrome, the most prevalent cause of mental retardation, results from the presence of an extra maternal chromosome 21 (trisomy 21), which comprises the Kcnj6 gene (GIRK2). The present study examined the behaviors and cellular physiology properties in mice harboring a single trisomy of the Kcnj6 gene. Kcnj6 triploid mice exhibit deficits in hippocampal-dependent learning and memory, altered responses to rewards, hampered depotentiation, a form of excitatory synaptic plasticity, and have accentuated long-term synaptic depression. Collectively the findings suggest that triplication of Kcnj6 gene may play an active role in some of the abnormal neurological phenotypes found in Down syndrome.read more
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Down syndrome: the brain in trisomic mode
TL;DR: New data from functional neuroimaging studies are challenging the authors' views of the cognitive phenotypes associated with Down syndrome and their pathophysiological correlates, and these advances hold promise for the development of treatments for intellectual disability.
Journal ArticleDOI
Deficits in Cognition and Synaptic Plasticity in a Mouse Model of Down Syndrome Ameliorated by GABAB Receptor Antagonists
Alexander M. Kleschevnikov,Pavel V. Belichenko,Mehrdad Faizi,Lucia F. Jacobs,Khin Htun,Mehrdad Shamloo,William C. Mobley +6 more
TL;DR: Evidence is found for a contribution of GABAB receptors to changes in hippocampal-based cognition in the Ts65Dn mouse and the ability to rescue cognitive performance through treatment with selective GABAB receptor antagonists motivates studies to further explore the therapeutic potential of these compounds in people with DS.
Journal ArticleDOI
Rodent models in Down syndrome research: impact and future opportunities.
Yann Herault,Jean M. Delabar,Elizabeth M. C. Fisher,Elizabeth M. C. Fisher,Victor L. J. Tybulewicz,Eugene Yu,Eugene Yu,Eugene Yu,Véronique Brault +8 more
TL;DR: An overview of research in the last 15 years dedicated to the development and application of rodent models for Down syndrome is provided and improved models are developed to better understand the pathophysiology of this genetic condition.
Journal ArticleDOI
Mouse models of Down syndrome: gene content and consequences.
TL;DR: The strengths and weaknesses of mouse models of DS based on the number and nature of the Hsa21 orthologs that are, and are not, trisomic in each, are considered and their validity for use in preclinical evaluations of drug responses is discussed.
Journal ArticleDOI
Decoding the development of the human hippocampus
Suijuan Zhong,Wenyu Ding,Le Sun,Yufeng Lu,Hao Dong,Xiaoying Fan,Zeyuan Liu,Ruiguo Chen,Shu Zhang,Qiang Ma,Fuchou Tang,Fuchou Tang,Qian Wu,Qian Wu,Xiaoqun Wang +14 more
TL;DR: The molecular features of the human hippocampus at gestational weeks 16–20 are similar to those of the mouse at postnatal days 0–5 and reveal gene expression differences between the two species, providing a blueprint for understanding human hippocampal development and a tool for investigating related diseases.
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