Loss of cGMP-dependent protein kinase II alters ultrasonic vocalizations in mice, a model for speech impairment in human microdeletion 4q21 syndrome

Tran, Tiffany; Sherwood, Jessica K.; Doolittle, Michael J.; Sathler, Matheus F.; Hofmann, Franz; Stone-Roy, Leslie M.; Kim, Seonil

doi:10.1016/j.neulet.2021.136048

Cited by 11 publications

(11 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Saline-exposed mice after a 90 min isolation exhibited significantly increased neuronal activity in the hypothalamus compared to mice in the nest (Fig. 5 and Table 2), which is consistent with the previous reports (Tran et al, 2021;Zimmer et al, 2019).…”

Section: Reduction Of Neuronal Activation In the Arcuate Nucleus Of V...supporting

confidence: 91%

“…The protein concentration in each faction was determined by a BCA protein assay kit (Thermo Fisher Scientific, PI23227). Immunoblots were performed as described previously (Farooq et al, 2016;Kim et al, 2005;Kim, Sato, et al, 2015;Kim et al, 2018;Kim, Titcombe, et al, 2015;Kim, Violette, et al, 2015;Kim & Ziff, 2014;Roberts et al, 2021;Sathler et al, 2022;Shou et al, 2018;Sun et al, 2019;Sztukowski et al, 2018;Tran et al, 2021). Equal amounts of protein samples were loaded on 10% glycine-SDS-PAGE gel.…”

Section: Tissue Sample Preparation and Immunoblotsmentioning

confidence: 99%

“…The ages of the pups used for experiments ranged from postnatal day 5 to postnatal day 7 (P5-P7) as shown previously (Tran et al, 2021). Neonatal P5-7 mice were separated from the home cage and placed in a round transparent container with an open top.…”

Section: Usv Recording and Analysismentioning

confidence: 99%

See 2 more Smart Citations

Prenatal exposure to valproic acid reduces synaptic δ-catenin levels and disrupts ultrasonic vocalization in neonates

Roh,

Mendez-Vazquez,

Sathler

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

Valproic acid (VPA) is an effective and commonly prescribed drug for epilepsy and bipolar disorder. However, children born from mothers treated with VPA during pregnancy exhibit an increased incidence of autism spectrum disorder (ASD). Although VPA may impair brain development at the cellular level, the mechanism of VPA-induced ASD has not been completely addressed. A previous study has found that VPA treatment strongly reduces δ-catenin mRNA levels in cultured human neurons. δ-catenin is important for the control of glutamatergic synapses and is strongly associated with ASD. VPA inhibits dendritic morphogenesis in developing neurons, an effect that is also found in neurons lacking δ-catenin expression. We thus hypothesize that prenatal exposure to VPA significantly reduces δ-catenin levels in the brain, which impairs glutamatergic synapses to cause ASD. Here, we found that prenatal exposure to VPA markedly reduced δ-catenin levels in the brain of mouse pups. VPA treatment also impaired dendritic branching in developing mouse cortical neurons, which was reversed by elevating δ-catenin expression. Prenatal VPA exposure significantly reduced synaptic AMPA receptor levels and postsynaptic density 95 (PSD95) in the brain of mouse pups, indicating dysfunctions in glutamatergic synaptic transmission. VPA exposure also significantly altered ultrasonic vocalization (USV) in newly born pups when they were isolated from their nest. Moreover, VPA-exposed pups show impaired hypothalamic response to isolation, which is required to produce animals’ USVs following isolation from the nest. Therefore, these results suggest that VPA-induced ASD pathology can be mediated by the loss of δ-catenin functions.HighlightsPrenatal exposure of valproic acid (VPA) in mice significantly reduces synaptic δ-catenin protein and AMPA receptor levels in the pups’ brains.VPA treatment significantly impairs dendritic branching in cultured cortical neurons, which is reversed by increased δ-catenin expression.VPA exposed pups exhibit impaired communication such as ultrasonic vocalization.Neuronal activation linked to ultrasonic vocalization is absent in VPA-exposed pups.The loss of δ-catenin functions underlies VPA-induced autism spectrum disorder (ASD) in early childhood.

show abstract

Section: Reduction Of Neuronal Activation In the Arcuate Nucleus Of V...supporting

confidence: 91%

Section: Tissue Sample Preparation and Immunoblotsmentioning

confidence: 99%

See 1 more Smart Citation

Prenatal exposure to valproic acid reduces synaptic δ-catenin levels and disrupts ultrasonic vocalization in neonates

Roh,

Mendez-Vazquez,

Sathler

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…In several cases, PRKG2 was reported as a key gene for language defects in the 4q21 deletion region, which encodes cGMP-dependent protein kinase II (cGKII). Therefore, in Germany in 2021 [11], a mouse model with 4q21 deletion of key genes was established to verify whether the knockout of cGKII affected vocalization. The experiment found that the established mouse model was consistent with the case.…”

Section: Genetic Test Resultsmentioning

confidence: 99%

Chromosome 4q deletion syndrome: 4q13.3-q21.23 deletion syndrome with mental retardation, congenital heart disease: a case report and literature review

Wang

Huang²,

Luo³

et al. 2023

Preprint

View full text Add to dashboard Cite

Objective. Chromosome 4q deletion syndrome is a rare disease, and the reported genotypes cannot fully explain the clinical manifestations. This article aims to present a case that provides ideas for the clinical diagnosis of similar conditions, by adding new genotypes to the 4q deletion fragment gene pool. Case presentation.A female child aged 7-month and 3-day-old was born after repeated treatments for “cleft palate, atrial septal defect, mixed deafness, corpus callosum developmental malformation” and other diseases. By searching the PubMed, and Web of Science, CNKI, the published literature on chromosome 4 deletion was sorted and analyzed. Whole-genome sequencing,which was diagnosed as 4q13.3-q21.23 deletion syndrome. Conclusion.The diagnosis of congenital heart defects, progressive growth retardation, and mental retardation with multisystem involvement, and deletion of a gene fragment of chromosome 4 became a disorder to be considered in clinical work. Timely analysis of genetic findings could help confirm the diagnosis.

show abstract

“…Immunoblots were performed as described previously (Farooq et al, 2016;Kim et al, 2005;Kim et al, 2016;Kim, Sato, et al, 2015;Kim et al, 2018;Kim, Violette, et al, 2015;Roberts et al, 2021;Sathler et al, 2022;Shou et al, 2018;Sun et al, 2019;Sztukowski et al, 2018;Tran et al, 2021). The protein concentration in total cell lysates was determined by a BCA protein assay kit (Thermo Fisher Scientific, PI23227).…”

Section: Immunoblotsmentioning

confidence: 99%

Ketamine’s rapid antidepressant effects are mediated by Ca²⁺-permeable AMPA receptors in the hippocampus

Zaytseva

Bouckova

Wiles

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Ketamine is shown to enhance excitatory synaptic drive in the hippocampus, which is presumed to underlie its rapid antidepressant effects. Moreover, ketamines therapeutic actions are likely mediated by enhancing neuronal Ca2+ signaling. However, ketamine is a noncompetitive NMDA receptor (NMDAR) antagonist that inhibits excitatory synaptic transmission and postsynaptic Ca2+ signaling. Thus, it is a puzzling question how ketamine enhances glutamatergic and Ca2+ activity in neurons to induce rapid antidepressant effects while blocking NMDARs in the hippocampus. Here, we find that ketamine treatment for one hour in cultured mouse hippocampal neurons significantly reduces calcineurin activity to elevate AMPA receptor (AMPAR) subunit GluA1 phosphorylation. This phosphorylation ultimately induces the expression of Ca2+ - permeable, GluA2-lacking, and GluA1-containing AMPARs (CP-AMPARs). Such ketamine-induced expression of CP-AMPARs enhances glutamatergic activity and synaptic plasticity in cultured hippocampal neurons. When a sub-anesthetic dose of ketamine is given to mice, it increases synaptic GluA1 levels, but not GluA2, and GluA1 phosphorylation in the hippocampus within one hour after treatment. These changes are likely mediated by ketamine-induced reduction of calcineurin activity in the hippocampus. Using the open field and tail suspension tests, we demonstrate that a low dose of ketamine rapidly reduces anxiety-like and depression-like behaviors in both male and female mice. However, when in vivo treatment of a CP-AMPAR antagonist abolishes the ketamines effects on animals behavior. We thus discover that ketamine at the low dose promotes the expression of CP-AMPARs via reduction of calcineurin activity in the hippocampus, which in turn enhances synaptic strength to induce rapid antidepressant actions.

show abstract

Loss of cGMP-dependent protein kinase II alters ultrasonic vocalizations in mice, a model for speech impairment in human microdeletion 4q21 syndrome

Cited by 11 publications

References 44 publications

Prenatal exposure to valproic acid reduces synaptic δ-catenin levels and disrupts ultrasonic vocalization in neonates

Prenatal exposure to valproic acid reduces synaptic δ-catenin levels and disrupts ultrasonic vocalization in neonates

Chromosome 4q deletion syndrome: 4q13.3-q21.23 deletion syndrome with mental retardation, congenital heart disease: a case report and literature review

Ketamine’s rapid antidepressant effects are mediated by Ca²⁺-permeable AMPA receptors in the hippocampus

Contact Info

Product

Resources

About

Loss of cGMP-dependent protein kinase II alters ultrasonic vocalizations in mice, a model for speech impairment in human microdeletion 4q21 syndrome

Cited by 11 publications

References 44 publications

Prenatal exposure to valproic acid reduces synaptic δ-catenin levels and disrupts ultrasonic vocalization in neonates

Prenatal exposure to valproic acid reduces synaptic δ-catenin levels and disrupts ultrasonic vocalization in neonates

Chromosome 4q deletion syndrome: 4q13.3-q21.23 deletion syndrome with mental retardation, congenital heart disease: a case report and literature review

Ketamine’s rapid antidepressant effects are mediated by Ca2+-permeable AMPA receptors in the hippocampus

Contact Info

Product

Resources

About

Ketamine’s rapid antidepressant effects are mediated by Ca²⁺-permeable AMPA receptors in the hippocampus