Sleep Alterations in a Mouse Model of Spinocerebellar Ataxia Type 3
Spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disorder showing progressive neuronal loss in several brain areas and a broad spectrum of motor and non-motor symptoms, including ataxia and altered sleep. While sleep disturbances are known to play pathophysiologic roles in other neurodege...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-10-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/11/19/3132 |
| _version_ | 1797479918875967488 |
|---|---|
| author | Maria-Efstratia Tsimpanouli Anjesh Ghimire Anna J. Barget Ridge Weston Henry L. Paulson Maria do Carmo Costa Brendon O. Watson |
| author_facet | Maria-Efstratia Tsimpanouli Anjesh Ghimire Anna J. Barget Ridge Weston Henry L. Paulson Maria do Carmo Costa Brendon O. Watson |
| author_sort | Maria-Efstratia Tsimpanouli |
| collection | DOAJ |
| description | Spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disorder showing progressive neuronal loss in several brain areas and a broad spectrum of motor and non-motor symptoms, including ataxia and altered sleep. While sleep disturbances are known to play pathophysiologic roles in other neurodegenerative disorders, their impact on SCA3 is unknown. Using spectrographic measurements, we sought to quantitatively characterize sleep electroencephalography (EEG) in SCA3 transgenic mice with confirmed disease phenotype. We first measured motor phenotypes in 18–31-week-old homozygous SCA3 YACMJD84.2 mice and non-transgenic wild-type littermate mice during lights-on and lights-off periods. We next implanted electrodes to obtain 12-h (zeitgeber time 0-12) EEG recordings for three consecutive days when the mice were 26–36 weeks old. EEG-based spectroscopy showed that compared to wild-type littermates, SCA3 homozygous mice display: (i) increased duration of rapid-eye movement sleep (REM) and fragmentation in all sleep and wake states; (ii) higher beta power oscillations during REM and non-REM (NREM); and (iii) additional spectral power band alterations during REM and wake. Our data show that sleep architecture and EEG spectral power are dysregulated in homozygous SCA3 mice, indicating that common sleep-related etiologic factors may underlie mouse and human SCA3 phenotypes. |
| first_indexed | 2024-03-09T21:52:40Z |
| format | Article |
| id | doaj.art-4ba169956e70434ea64ec59410e1cf96 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T21:52:40Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-4ba169956e70434ea64ec59410e1cf962023-11-23T20:03:24ZengMDPI AGCells2073-44092022-10-011119313210.3390/cells11193132Sleep Alterations in a Mouse Model of Spinocerebellar Ataxia Type 3Maria-Efstratia Tsimpanouli0Anjesh Ghimire1Anna J. Barget2Ridge Weston3Henry L. Paulson4Maria do Carmo Costa5Brendon O. Watson6Department of Neurology, Michigan Medicine, University of Michigan, Ann Arbor, MI 48109, USADepartment of Psychiatry, Michigan Medicine, University of Michigan, Ann Arbor, MI 48109, USADepartment of Neurology, Michigan Medicine, University of Michigan, Ann Arbor, MI 48109, USADepartment of Psychiatry, Michigan Medicine, University of Michigan, Ann Arbor, MI 48109, USADepartment of Neurology, Michigan Medicine, University of Michigan, Ann Arbor, MI 48109, USADepartment of Neurology, Michigan Medicine, University of Michigan, Ann Arbor, MI 48109, USADepartment of Psychiatry, Michigan Medicine, University of Michigan, Ann Arbor, MI 48109, USASpinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disorder showing progressive neuronal loss in several brain areas and a broad spectrum of motor and non-motor symptoms, including ataxia and altered sleep. While sleep disturbances are known to play pathophysiologic roles in other neurodegenerative disorders, their impact on SCA3 is unknown. Using spectrographic measurements, we sought to quantitatively characterize sleep electroencephalography (EEG) in SCA3 transgenic mice with confirmed disease phenotype. We first measured motor phenotypes in 18–31-week-old homozygous SCA3 YACMJD84.2 mice and non-transgenic wild-type littermate mice during lights-on and lights-off periods. We next implanted electrodes to obtain 12-h (zeitgeber time 0-12) EEG recordings for three consecutive days when the mice were 26–36 weeks old. EEG-based spectroscopy showed that compared to wild-type littermates, SCA3 homozygous mice display: (i) increased duration of rapid-eye movement sleep (REM) and fragmentation in all sleep and wake states; (ii) higher beta power oscillations during REM and non-REM (NREM); and (iii) additional spectral power band alterations during REM and wake. Our data show that sleep architecture and EEG spectral power are dysregulated in homozygous SCA3 mice, indicating that common sleep-related etiologic factors may underlie mouse and human SCA3 phenotypes.https://www.mdpi.com/2073-4409/11/19/3132polyglutamineataxin-3sleepEEGbeta-oscillations |
| spellingShingle | Maria-Efstratia Tsimpanouli Anjesh Ghimire Anna J. Barget Ridge Weston Henry L. Paulson Maria do Carmo Costa Brendon O. Watson Sleep Alterations in a Mouse Model of Spinocerebellar Ataxia Type 3 Cells polyglutamine ataxin-3 sleep EEG beta-oscillations |
| title | Sleep Alterations in a Mouse Model of Spinocerebellar Ataxia Type 3 |
| title_full | Sleep Alterations in a Mouse Model of Spinocerebellar Ataxia Type 3 |
| title_fullStr | Sleep Alterations in a Mouse Model of Spinocerebellar Ataxia Type 3 |
| title_full_unstemmed | Sleep Alterations in a Mouse Model of Spinocerebellar Ataxia Type 3 |
| title_short | Sleep Alterations in a Mouse Model of Spinocerebellar Ataxia Type 3 |
| title_sort | sleep alterations in a mouse model of spinocerebellar ataxia type 3 |
| topic | polyglutamine ataxin-3 sleep EEG beta-oscillations |
| url | https://www.mdpi.com/2073-4409/11/19/3132 |
| work_keys_str_mv | AT mariaefstratiatsimpanouli sleepalterationsinamousemodelofspinocerebellarataxiatype3 AT anjeshghimire sleepalterationsinamousemodelofspinocerebellarataxiatype3 AT annajbarget sleepalterationsinamousemodelofspinocerebellarataxiatype3 AT ridgeweston sleepalterationsinamousemodelofspinocerebellarataxiatype3 AT henrylpaulson sleepalterationsinamousemodelofspinocerebellarataxiatype3 AT mariadocarmocosta sleepalterationsinamousemodelofspinocerebellarataxiatype3 AT brendonowatson sleepalterationsinamousemodelofspinocerebellarataxiatype3 |