Abnormal expression of the G-protein-activated inwardly rectifying potassium channel 2 (GIRK2) in hippocampus, frontal cortex, and substantia nigra of Ts65Dn mouse: a model of Down syndrome.
paper
Cited
Public
Unavailable
- Authors
- Harashima, Chie; Jacobowitz, David M; Witta, Jassir; Borke, Rosemary C; Best, Tyler K; Siarey, Richard J; Galdzicki, Zygmunt
- Year
- 2006
- Journal
- The Journal of comparative neurology
- PMID
- 16374808
- DOI
- 10.1002/cne.20844
- PMCID
- PMC2929960
Ts65Dn, a mouse model of Down syndrome (DS), demonstrates abnormal hippocampal synaptic plasticity and behavioral abnormalities related to spatial learning and memory. The molecular mechanisms leading to these impairments have not been identified. In this study, we focused on the G-protein-activated inwardly rectifying potassium channel 2 (GIRK2) gene that is highly expressed in the hippocampus region. We studied the expression pattern of GIRK subunits in Ts65Dn and found that GIRK2 was overexpressed in all analyzed Ts65Dn brain regions. Interestingly, elevated levels of GIRK2 protein in the Ts65Dn hippocampus and frontal cortex correlated with elevated levels of GIRK1 protein. This suggests that heteromeric GIRK1-GIRK2 channels are overexpressed in Ts65Dn hippocampus and frontal cortex, which could impair excitatory input and modulate spike frequency and synaptic kinetics in the affected regions. All GIRK2 splicing isoforms examined were expressed at higher levels in the Ts65Dn in comparison to the diploid hippocampus. The pattern of GIRK2 expression in the Ts65Dn mouse brain revealed by in situ hybridization and immunohistochemistry was similar to that previously reported in the rodent brain. However, in the Ts65Dn mouse a strong immunofluorescent staining of GIRK2 was detected in the lacunosum molecular layer of the CA3 area of the hippocampus. In addition, tyrosine hydroxylase containing dopaminergic neurons that coexpress GIRK2 were more numerous in the substantia nigra compacta and ventral tegmental area in the Ts65Dn compared to diploid controls. In summary, the regional localization and the increased brain levels coupled with known function of the GIRK channel may suggest an important contribution of GIRK2 containing channels to Ts65Dn and thus to DS neurophysiological phenotypes.
No figures extracted from this document.
No chunks β full text not yet ingested.
No entities extracted from this document yet.
No uploaded files.
Not in any collection.
No citations found.
In this knowledge base
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| A critical residue mediates proper assembly and gating of GIRK2 channels. | Nguyen H et al. | β | 2026 | β |
| Altered synaptic functions in a humanized mouse model of down syndrome (TcMAC21): Implications for seizure susceptibility. | Shao LR et al. | β | 2025 | β |
| Carbonyl reductase 1: a novel regulator of blood pressure in Down syndrome. | Malbon AJ et al. | β | 2025 | β |
| Identification of Neurite Outgrowth and Synaptic Plasticity-related Genes Showing Sustained Hypermethylation of Promoter Region in the Hippocampal Dentate Gyrus of Rats Exposed Maternally To Neurotoxicants To Induce Persistent Disruption of Hippocampal Neurogenesis. | Ojiro R et al. | β | 2025 | β |
| The Role of GABA Pathway Components in Pathogenesis of Neurodevelopmental Disorders. | Marilovtseva EV et al. | β | 2025 | β |
| Understanding the neurobiology of infantile epileptic spasms syndrome (IESS): A comprehensive review. | Modgil A et al. | β | 2025 | β |
| Brain volumes, cognitive, and adaptive skills in school-age children with Down syndrome. | Grzadzinski R et al. | β | 2024 | β |
| Dysfunctions of cellular context-sensitivity in neurodevelopmental learning disabilities. | Granato A et al. | β | 2024 | β |
| Understanding the genetic mechanisms and cognitive impairments in Down syndrome: towards a holistic approach. | Abukhaled Y et al. | β | 2024 | β |
| Alcohol reverses the effects of KCNJ6 (GIRK2) noncoding variants on excitability of human glutamatergic neurons. | Popova D et al. | β | 2023 | β |
| Brain circuit pathology in Down syndrome: from neurons to neural networks. | Bartesaghi R | β | 2023 | β |
| Increased propensity for infantile spasms and altered neocortical excitation-inhibition balance in a mouse model of down syndrome carrying human chromosome 21. | Shao LR et al. | β | 2023 | β |
| Animal Models in Epileptic Spasms and the Development of Novel Treatment Options. | Barrett KT et al. | β | 2022 | β |
| Enhanced GIRK2 channel signaling in Down syndrome: A feasible role in the development of abnormal nascent neural circuits. | Kleschevnikov AM | β | 2022 | β |
| GABA<sub>B</sub> Receptors and Cognitive Processing in Health and Disease. | Vlachou S | β | 2022 | β |
| GIRK2 Channels in Down Syndrome and Alzheimer's Disease. | Kleschevnikov A | β | 2022 | β |
| Identification of a G-Protein-Independent Activator of GIRK Channels. | Zhao Y et al. | β | 2020 | β |
| Infantile Spasms: An Update on Pre-Clinical Models and EEG Mechanisms. | Janicot R et al. | β | 2020 | β |
| Treatment of infantile spasms: why do we know so little? | Specchio N et al. | β | 2020 | β |
| Direct activation of G-protein-gated inward rectifying K+ channels promotes nonrapid eye movement sleep. | Zou B et al. | β | 2019 | β |
| Down syndrome. | Rafii MS et al. | β | 2019 | β |
| Down syndrome: Neurobiological alterations and therapeutic targets. | Vacca RA et al. | β | 2019 | β |
| Neuronal and vascular deficits following chronic adaptation to high altitude. | Cramer NP et al. | β | 2019 | β |
| Developmental excitatory-to-inhibitory GABA polarity switch is delayed in Ts65Dn mice, a genetic model of Down syndrome. | Lysenko LV et al. | β | 2018 | β |
| Kcnj6(GIRK2) trisomy is not sufficient for conferring the susceptibility to infantile spasms seen in the Ts65Dn mouse model of down syndrome. | Joshi K et al. | β | 2018 | β |
| Potassium channel regulators are differentially expressed in hippocampi of Ts65Dn and Tc1 Down syndrome mouse models | Stern S et al. | β | 2018 | β |
| Evidence that increased Kcnj6 gene dose is necessary for deficits in behavior and dentate gyrus synaptic plasticity in the Ts65Dn mouse model of Down syndrome. | Kleschevnikov AM et al. | β | 2017 | β |
| G-Protein-Coupled Inwardly Rectifying Potassium (GIRK) Channel Activation by the p75 Neurotrophin Receptor Is Required for Amyloid Ξ² Toxicity. | May LM et al. | β | 2017 | β |
| Neuroanatomical alterations and synaptic plasticity impairment in the perirhinal cortex of the Ts65Dn mouse model of Down syndrome. | RoncacΓ© V et al. | β | 2017 | β |
| The GABAergic Hypothesis for Cognitive Disabilities in Down Syndrome. | Contestabile A et al. | β | 2017 | β |
| GABAergic hyperinnervation of dentate granule cells in the Ts65Dn mouse model of down syndrome: Exploring the role of App. | Mojabi FS et al. | β | 2016 | β |
| Infantile spasms in down syndrome: Rescue by knockdown of the GIRK2 channel. | Joshi K et al. | β | 2016 | β |
| Altered intrinsic and network properties of neocortical neurons in the Ts65Dn mouse model of Down syndrome. | Cramer NP et al. | β | 2015 | β |
| Cerebal overinhibition could be the basis for the high prevalence of epilepsy in persons with Down syndrome. | Araujo BH et al. | β | 2015 | β |
| GIRK Channels: A Potential Link Between Learning and Addiction. | Tipps ME et al. | β | 2015 | β |
| Involvement of Potassium and Cation Channels in Hippocampal Abnormalities of Embryonic Ts65Dn and Tc1 Trisomic Mice. | Stern S et al. | β | 2015 | β |
| Reversing excitatory GABAAR signaling restores synaptic plasticity and memory in a mouse model of Down syndrome. | Deidda G et al. | β | 2015 | β |
| The GIRK2 subunit is involved in IS-like seizures induced by GABA(B) receptor agonists. | Blichowski M et al. | β | 2015 | β |
| New insights into the therapeutic potential of Girk channels. | LujΓ‘n R et al. | β | 2014 | β |
| Autism spectrum disorders: the quest for genetic syndromes. | Zafeiriou DI et al. | β | 2013 | β |
| GABAergic dysfunction in pediatric neuro-developmental disorders. | Smith-Hicks CL | β | 2013 | β |
| Protein profiles in Tc1 mice implicate novel pathway perturbations in the Down syndrome brain. | Ahmed MM et al. | β | 2013 | β |
| Weaker control of the electrical properties of cerebellar granule cells by tonically active GABAA receptors in the Ts65Dn mouse model of Down's syndrome. | Szemes M et al. | β | 2013 | β |
| Deficits in cognition and synaptic plasticity in a mouse model of Down syndrome ameliorated by GABAB receptor antagonists. | Kleschevnikov AM et al. | β | 2012 | β |
| Discoveries in Down syndrome: moving basic science to clinical care. | Kleschevnikov AM et al. | β | 2012 | β |
| Dysfunctional hippocampal inhibition in the Ts65Dn mouse model of Down syndrome. | Best TK et al. | β | 2012 | β |
| From abnormal hippocampal synaptic plasticity in down syndrome mouse models to cognitive disability in down syndrome. | Cramer N et al. | β | 2012 | β |
| Increased efficiency of the GABAA and GABAB receptor-mediated neurotransmission in the Ts65Dn mouse model of Down syndrome. | Kleschevnikov AM et al. | β | 2012 | β |
| Lack of behavioral and cognitive effects of chronic ethosuximide and gabapentin treatment in the Ts65Dn mouse model of Down syndrome. | Vidal V et al. | β | 2012 | β |
| Trisomy of the G protein-coupled K+ channel gene, Kcnj6, affects reward mechanisms, cognitive functions, and synaptic plasticity in mice. | Cooper A et al. | β | 2012 | β |
| Down syndrome: searching for the genetic culprits. | Lana-Elola E et al. | β | 2011 | β |
| Is it possible to improve neurodevelopmental abnormalities in Down syndrome? | Bartesaghi R et al. | β | 2011 | β |
| Emerging pharmacotherapies for neurodevelopmental disorders. | Wetmore DZ et al. | β | 2010 | β |
| GABAB-GIRK2-mediated signaling in Down syndrome. | Cramer NP et al. | β | 2010 | β |
| Generation of a panel of antibodies against proteins encoded on human chromosome 21. | Wiseman FK et al. | β | 2010 | β |
| Olig1 and Olig2 triplication causes developmental brain defects in Down syndrome. | Chakrabarti L et al. | β | 2010 | β |
| STDP and Mental Retardation: Dysregulation of Dendritic Excitability in Fragile X Syndrome. | Meredith RM et al. | β | 2010 | β |
| Aneuploidy: from a physiological mechanism of variance to Down syndrome. | Dierssen M et al. | β | 2009 | β |
| Down syndrome--recent progress and future prospects. | Wiseman FK et al. | β | 2009 | β |
| Infantile spasms and Down syndrome: a new animal model. | Cortez MA et al. | β | 2009 | β |
| Distribution and neurochemical characterization of neurons expressing GIRK channels in the rat brain. | Saenz del Burgo L et al. | β | 2008 | β |
| Speeding of miniature excitatory post-synaptic currents in Ts65Dn cultured hippocampal neurons. | Best TK et al. | β | 2008 | β |
| Heterogeneous distribution of kir3 potassium channel proteins within dopaminergic neurons in the mesencephalon of the rat brain. | Eulitz D et al. | β | 2007 | β |
| Mental retardation in Down syndrome: from gene dosage imbalance to molecular and cellular mechanisms. | Rachidi M et al. | β | 2007 | β |
| Synaptic and cognitive abnormalities in mouse models of Down syndrome: exploring genotype-phenotype relationships. | Belichenko PV et al. | β | 2007 | β |
| The GIRK1 brain variant GIRK1d and its functional impact on heteromultimeric GIRK channels. | Steinecker B et al. | β | 2007 | β |
| Ts65Dn, a mouse model of Down syndrome, exhibits increased GABAB-induced potassium current. | Best TK et al. | β | 2007 | β |
| Altered signaling pathways underlying abnormal hippocampal synaptic plasticity in the Ts65Dn mouse model of Down syndrome. | Siarey RJ et al. | β | 2006 | β |
| Delayed onset of beating and decreased expression of T-type Ca2+ channel in mouse ES cell-derived cardiocytes carrying human chromosome 21. | Mizuta E et al. | β | 2006 | β |
| Elevated expression of the G-protein-activated inwardly rectifying potassium channel 2 (GIRK2) in cerebellar unipolar brush cells of a Down syndrome mouse model. | Harashima C et al. | β | 2006 | β |
| Hypothermic responses to 8-OH-DPAT in the Ts65Dn mouse model of Down syndrome. | Stasko MR et al. | β | 2006 | β |