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Glymphatic dysfunction coincides with lower GABA levels and sleep disturbances in succinic semialdehyde dehydrogenase deficiency.
- Source :
-
Journal of sleep research [J Sleep Res] 2024 Aug; Vol. 33 (4), pp. e14105. Date of Electronic Publication: 2023 Dec 26. - Publication Year :
- 2024
-
Abstract
- Succinic semialdehyde dehydrogenase deficiency (SSADHD) is an inherited metabolic disorder of γ-aminobutyrate (GABA) catabolism. Cerebral waste clearance along glymphatic perivascular spaces depends on aquaporin 4 (AQP4) water channels, the function of which was shown to be influenced by GABA. Sleep disturbances are associated independently with SSADHD and glymphatic dysfunction. This study aimed to determine whether indices of the hyperGABAergic state characteristic of SSADHD coincide with glymphatic dysfunction and sleep disturbances and to explicate the modulatory effect that GABA may have on the glymphatic system. The study included 42 individuals (21 with SSADHD; 21 healthy controls) who underwent brain MRIs and magnetic resonance spectroscopy (MRS) for assessment of glymphatic dysfunction and cortical GABA, plasma GABA measurements, and circadian clock gene expression. The SSADHD subjects responded to an additional Children's Sleep Habits Questionnaire (CSHQ). Compared with the control group, SSADHD subjects did not differ in sex and age but had a higher severity of enlarged perivascular spaces in the centrum semiovale (p < 0.001), basal ganglia (p = 0.01), and midbrain (p = 0.001), as well as a higher MRS-derived GABA/NAA peak (p < 0.001). Within the SSADHD group, the severity of glymphatic dysfunction was specific for a lower MRS-derived GABA/NAA (p = 0.04) and lower plasma GABA (p = 0.004). Additionally, the degree of their glymphatic dysfunction correlated with the CSHQ-estimated sleep disturbances scores (R = 5.18, p = 0.03). In the control group, EPVS burden did not correlate with age or cerebral and plasma GABA values. The modulatory effect that GABA may exert on the glymphatic system has therapeutic implications for sleep-related disorders and neurodegenerative conditions associated with glymphatic dysfunction.<br /> (© 2023 European Sleep Research Society.)
- Subjects :
- Humans
Male
Female
Child
Magnetic Resonance Spectroscopy
Adolescent
Brain diagnostic imaging
Brain physiopathology
Brain metabolism
Aquaporin 4
Laryngostenosis physiopathology
Child, Preschool
Developmental Disabilities
gamma-Aminobutyric Acid metabolism
Amino Acid Metabolism, Inborn Errors physiopathology
Amino Acid Metabolism, Inborn Errors complications
Sleep Wake Disorders physiopathology
Glymphatic System physiopathology
Succinate-Semialdehyde Dehydrogenase deficiency
Magnetic Resonance Imaging
Subjects
Details
- Language :
- English
- ISSN :
- 1365-2869
- Volume :
- 33
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Journal of sleep research
- Publication Type :
- Academic Journal
- Accession number :
- 38148273
- Full Text :
- https://doi.org/10.1111/jsr.14105