Atypical electrophysiological and behavioral responses to diazepam in a leading mouse model of Down syndrome
Abstract Mounting evidence implicates dysfunctional GABAAR-mediated neurotransmission as one of the underlying causes of learning and memory deficits observed in the Ts65Dn mouse model of Down syndrome (DS). The specific origin and nature of such dysfunction is still under investigation, which is an...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2021-05-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-89011-y |
| _version_ | 1818858319524134912 |
|---|---|
| author | Daniella B. Victorino Daniel J. L. L. Pinheiro Jonah J. Scott-McKean Sarah Barker Melissa R. Stasko Jean Faber Carla A. Scorza Alberto C. S. Costa |
| author_facet | Daniella B. Victorino Daniel J. L. L. Pinheiro Jonah J. Scott-McKean Sarah Barker Melissa R. Stasko Jean Faber Carla A. Scorza Alberto C. S. Costa |
| author_sort | Daniella B. Victorino |
| collection | DOAJ |
| description | Abstract Mounting evidence implicates dysfunctional GABAAR-mediated neurotransmission as one of the underlying causes of learning and memory deficits observed in the Ts65Dn mouse model of Down syndrome (DS). The specific origin and nature of such dysfunction is still under investigation, which is an issue with practical consequences to preclinical and clinical research, as well as to the care of individuals with DS and anxiety disorder or those experiencing seizures in emergency room settings. Here, we investigated the effects of GABAAR positive allosteric modulation (PAM) by diazepam on brain activity, synaptic plasticity, and behavior in Ts65Dn mice. We found Ts65Dn mice to be less sensitive to diazepam, as assessed by electroencephalography, long-term potentiation, and elevated plus-maze. Still, diazepam pre-treatment displayed typical effectiveness in reducing susceptibility and severity to picrotoxin-induced seizures in Ts65Dn mice. These findings fill an important gap in the understanding of GABAergic function in a key model of DS. |
| first_indexed | 2024-12-19T08:54:24Z |
| format | Article |
| id | doaj.art-5901e46d3ede478a8d1e006e2f931c75 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-19T08:54:24Z |
| publishDate | 2021-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-5901e46d3ede478a8d1e006e2f931c752022-12-21T20:28:39ZengNature PortfolioScientific Reports2045-23222021-05-0111111610.1038/s41598-021-89011-yAtypical electrophysiological and behavioral responses to diazepam in a leading mouse model of Down syndromeDaniella B. Victorino0Daniel J. L. L. Pinheiro1Jonah J. Scott-McKean2Sarah Barker3Melissa R. Stasko4Jean Faber5Carla A. Scorza6Alberto C. S. Costa7Discipline of Neuroscience, Department of Neurology and Neurosurgery, Federal University of São Paulo, Paulista Medical SchoolDiscipline of Neuroscience, Department of Neurology and Neurosurgery, Federal University of São Paulo, Paulista Medical SchoolDivision of Pediatric Neurology, Department of Pediatrics, Case Western Reserve UniversityDivision of Pediatric Neurology, Department of Pediatrics, Case Western Reserve UniversityDivision of Pediatric Neurology, Department of Pediatrics, Case Western Reserve UniversityDiscipline of Neuroscience, Department of Neurology and Neurosurgery, Federal University of São Paulo, Paulista Medical SchoolDiscipline of Neuroscience, Department of Neurology and Neurosurgery, Federal University of São Paulo, Paulista Medical SchoolDivision of Pediatric Neurology, Department of Pediatrics, Case Western Reserve UniversityAbstract Mounting evidence implicates dysfunctional GABAAR-mediated neurotransmission as one of the underlying causes of learning and memory deficits observed in the Ts65Dn mouse model of Down syndrome (DS). The specific origin and nature of such dysfunction is still under investigation, which is an issue with practical consequences to preclinical and clinical research, as well as to the care of individuals with DS and anxiety disorder or those experiencing seizures in emergency room settings. Here, we investigated the effects of GABAAR positive allosteric modulation (PAM) by diazepam on brain activity, synaptic plasticity, and behavior in Ts65Dn mice. We found Ts65Dn mice to be less sensitive to diazepam, as assessed by electroencephalography, long-term potentiation, and elevated plus-maze. Still, diazepam pre-treatment displayed typical effectiveness in reducing susceptibility and severity to picrotoxin-induced seizures in Ts65Dn mice. These findings fill an important gap in the understanding of GABAergic function in a key model of DS.https://doi.org/10.1038/s41598-021-89011-y |
| spellingShingle | Daniella B. Victorino Daniel J. L. L. Pinheiro Jonah J. Scott-McKean Sarah Barker Melissa R. Stasko Jean Faber Carla A. Scorza Alberto C. S. Costa Atypical electrophysiological and behavioral responses to diazepam in a leading mouse model of Down syndrome Scientific Reports |
| title | Atypical electrophysiological and behavioral responses to diazepam in a leading mouse model of Down syndrome |
| title_full | Atypical electrophysiological and behavioral responses to diazepam in a leading mouse model of Down syndrome |
| title_fullStr | Atypical electrophysiological and behavioral responses to diazepam in a leading mouse model of Down syndrome |
| title_full_unstemmed | Atypical electrophysiological and behavioral responses to diazepam in a leading mouse model of Down syndrome |
| title_short | Atypical electrophysiological and behavioral responses to diazepam in a leading mouse model of Down syndrome |
| title_sort | atypical electrophysiological and behavioral responses to diazepam in a leading mouse model of down syndrome |
| url | https://doi.org/10.1038/s41598-021-89011-y |
| work_keys_str_mv | AT daniellabvictorino atypicalelectrophysiologicalandbehavioralresponsestodiazepaminaleadingmousemodelofdownsyndrome AT danieljllpinheiro atypicalelectrophysiologicalandbehavioralresponsestodiazepaminaleadingmousemodelofdownsyndrome AT jonahjscottmckean atypicalelectrophysiologicalandbehavioralresponsestodiazepaminaleadingmousemodelofdownsyndrome AT sarahbarker atypicalelectrophysiologicalandbehavioralresponsestodiazepaminaleadingmousemodelofdownsyndrome AT melissarstasko atypicalelectrophysiologicalandbehavioralresponsestodiazepaminaleadingmousemodelofdownsyndrome AT jeanfaber atypicalelectrophysiologicalandbehavioralresponsestodiazepaminaleadingmousemodelofdownsyndrome AT carlaascorza atypicalelectrophysiologicalandbehavioralresponsestodiazepaminaleadingmousemodelofdownsyndrome AT albertocscosta atypicalelectrophysiologicalandbehavioralresponsestodiazepaminaleadingmousemodelofdownsyndrome |